RE: antibodies in mothers of dyslexic children have possible immune system deficiencies - research page

[Guest guest]

Effects of mothers' autoimmune disease during pregnancy on learning disabilities

and hand preference in their children.

Date: 9 Jun 2003 16:34:43 -0700

Newsgroups: alt.support.mult-sclerosis

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Do women wMS produce anti-Ro/La maternal antibodies? I'm wondering

why this study concluded:

" ...These findings should promote greater awareness of the risk for LD

(learning disabilities) in sons of women with autoimmune disease and

the possible need for early educational intervention in those

children. "

when only women with lupus were tested?

F

Effects of mothers' autoimmune disease during pregnancy on learning

disabilities and hand preference in their children.

Arch Pediatr Adolesc Med. 2003 Apr;157(4):397-402.

Ross G, Sammaritano L, Nass R, Lockshin M.

Department of Pediatrics, New York Presbyterian Hospital, New York, NY

10021, USA. email-address-deleted

OBJECTIVES: To determine whether children (and particularly sons) of

women with systemic lupus erythematosus (SLE) during pregnancy are

more likely to have learning disabilities (LD) and be

non-right-handed, and if maternal disease variables (ie, presence of

maternal antibodies, disease activity level, and use of

corticosteroids) predict the prevalence of LD in offspring.

DESIGN: Case-controlled study with subjects matched by age and sex.

PARTICIPANTS: We studied 58 children whose mothers had SLE during

pregnancy and 58 children of healthy mothers.Measures Data collected

included maternal disease variables in women with SLE during their

pregnancies. All children took a standardized intelligence test

(Wechsler Intelligence Scale for Children-III) and completed a

modified version of the Edinburgh Hand Preference Questionnaire. They

also took standardized tests of reading, arithmetic, and writing

achievement. Learning disability was defined as having an academic

achievement score of at least 1.5 SDs below the Full-Scale IQ.

RESULTS: Sons of women with SLE were significantly more likely to have

LD than daughters of women with SLE or children of either sex in the

control group. Maternal SLE was not associated with

non-right-handedness in sons or daughters. The presence of anti-Ro/La

antibodies and disease activity (flare) in mothers during pregnancy

were significantly related to higher prevalence of LD in offspring.

CONCLUSIONS: Autoimmune disease in women during pregnancy is

associated with an increased risk for LD in their sons. Maternal

antibodies, particularly anti-Ro/La, likely affect the fetal brain of

male offspring and result in later learning problems. These findings

should promote greater awareness of the risk for LD in sons of women

with autoimmune disease and the possible need for early educational

intervention in those children.

PMID: 12695238 [PubMed - indexed for MEDLINE]

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antibodies in mothers of dyslexic children have possible immune system

deficiencies - research page

Immune System Disorders and Learning Disabilities

http://www.bdainternationalconference.org/presentations/thu_s1_a_5.htm

Possible Immune System Deficiencies?

It has been claimed that there may be an immunological basis for learning

problems. Pennington, , Kimberling, Green and Haith (1987) found elevated

levels of antibodies in mothers with dyslexic children, and Lahita (1988) found

mothers with a particular immune system disability had a higher than average

rate of children with learning disorders. Stein and Talcott (1999) and

Galaburda (1997) cite evidence that dyslexics and their families have a greater

than

normal incidence of autoimmune disorders, while Knivsberg's (1997) analysis of

urine samples found more abnormalities in the urine patterns of dyslexics. A

number of other authors have also reported an association between immune

disorders and dyslexia (Armstrong, Seidel, & Swales, 1993; Hugdahl, 1995; Wood &

, 1992). Chronic Fatigue Syndrome has also been associated with a variety

of immune system deficiencies (Dykman, Tone, & Dykman, 1997; Ojo-Amaize,

Conley, & , 1994), as well as dysregulation of immune cell numbers and

cytokine

production (Gupta & Vayevegula, 1991).

The possible association between CFS, visual/ocular problems and immune

system dysfunction was also observed in Study Two. The changes in reading

ability

and response to lens use were associated with indicators of infection as shown

by sore or swollen lymph nodes (Table 2), as well as dysregulation of urinary

metabolites and fatty acid metabolism, which may be indicative of a reaction

to infection (Table 3) (Arao, Soushi, Sato, Moriishi, Audo, Yamada, Padilla,

Uno, Nii, & Kurata 1997; Qavi, Xu, Green, Lusso, Pearson, & Ablashi 1996;

et al., 1999; Singh, Ling, & Yang, 1998).

The high familial incidence of disabilities such as IS (, Foreman, &

Dear, 1996, 2000) suggest that a gene mechanism may influence the probability

of immune system dysfunction. However, while familial gene traits may

influence the probability of familial reading difficulties, the possibility of

familial transfer of infective agents is also a distinct possibility. While

viruses

such as Human Herpes-6 (HHV-6) are not transferred across the placenta,

children usually contract HHV-6 infections in the first couple of years of life

from

other family members. This is important as reactivation of HHV-6 has also been

implicated in the development of CFS (Suhadolnik, Reichenbach, Hitzges,

Sobow, , Henry et al., 1994; Suhadolnik, , O'Brien, Cheney,

Herst,

Reichenbach et al, 1997). This virus may also play some role in alteration of

retinal function. Qavi et al. (1996) showed that HHV-6 was able to infect

corneal epithelial cells, whilst Arao et al. (1997) also showed that HHV-6 was

able to infect retinal pigment epithelial cells. Significantly, Singh et al.

(1998) reported that HHV-6, along with an autoantibody against neuron-axon

filament protein, was increased in patients with autism. Thus the alteration in

visual processing may be associated with a persistent viral infection by HHV-6.

Dietary Intervention as a Treatment Option?

The identification of dysregulated metabolism in people with symptoms of IS

raises the question of dietary manipulation and food supplementation as an

addition to the already established treatments of tinted filters and remedial

support. Dietary intervention for people with dyslexia has been successfully

undertaken by Stordy (1995, 1998) and Makrides et al. (1995) using an essential

fatty acid supplementation. There have been a variety of other investigations

that implicate diet as a potentially important aspect of treatment for people

with learning disabilities. Benton (1997) reported a case study in which a

glyconutritional supplement, given to a child with dyslexia, resulted in claims

of

large improvements in reading and writing activities.

Dietary intervention has also been shown to have a positive effect for people

with ADHD (Boris & Mandel, 1994; , Urbanowicz, Hemsley, Mantilla,

Strobel, Graham, & , 1993; Egger, , Graham, Gumley, & Soothill,

1985;

Egger, Stoller, & McEwen, 1993; Knivesberg, N??dland, Reichelt, & Fosse, 2000;

Uhlig, Merkenschlager, Brandmaier, & Egger, 1997). Uhlig et al. (1997) found a

significant increase in beta brain electrical activity for children with ADHD

following the ingestion of previously identified provoking foods. Knivesberg

et al. (2000) reported on the evaluation of a casein free diet for children

with symptoms of ADHD and additional urinary peptide anomalies. Preliminary data

has identified a significant reduction in peptide levels, as well as

significant improvements in behaviour. et al. (1993) found a significant

worsening in ratings of behaviour and in psychological test performance for

provoking

foods using blinded crossover design. Boris and Mandel (1994), and Egger et

al. (1985) used elimination diets to identify those subjects with ADHD who

responded favourably and then challenged the responders with a variety of foods

in

a placebo-controlled and blinded study. In both cases, there were significant

improvements in behaviour on placebo days compared to challenge days. Egger

et al. (1993) obtained positive results for subjects with ADHD using a food

desensitisation technique and a double-blind, placebo-controlled trial.

There have also been studies of successful dietary intervention for children

with symptoms of autism, and reading problems are more frequent than expected

in families with autism (Le Couteur, 1988). Increased levels of peptides have

been found in urine analyses (Cade, Privette, Fregly, Rowland, Sun, Zele,

Wagemaker, & Edelstein, 2000; Knivsberg, Reichelt, & N??dland, 1999; Knivsberg,

Reichelt, N??dland, & H??ien, 1995; Reichelt, Knivsberg, N??dland, Stensrud, &

Reichelt, 1997), some of which may stem from dietary proteins (Reichelt, Ekrem,

&

, 1990; Shattock, Kennedy, Rowell, & Berney, 1990). When autistic subjects

in the Knivsberg et al. (1995) study were provided with a diet free of gluten

and milk proteins, there was a normalisation of urine patterns and peptide

levels within one year and significant improvements in social, cognitive, and

communicative skills in a four year follow-up. Those subjects who stopped the

diet regressed. Reichelt et al. (1990) also found a normalisation of peptide

patterns and improvement in social skills after one year of a similar dietary

intervention, while Knivsberg et al. (1999) obtained a similar result over two

years of intervention and Cade et al. (2000) after three months of intervention.

Other studies have also found a reduction in symptoms of autism following

dietary changes (Knivsberg, Reichelt, H??ien, & N??dland, 1998; Whiteley,

Rodgers,

Savery, & Shattock, 1999). Preliminary investigations at the University of

Newcastle, Australia, have identified altered urinary amino acid and blood lipid

profiles which can be influenced by dietary supplementation. There were also

increases in long chain fatty acids indicative of poor intracellular processing

of these lipids and supplementation with essential fatty acids could be

beneficial. Analyses of faecal bacteria indicated that important gut bacteria

are

often lacking, and sometimes almost absent, with treatment to normalise this

bacteria having beneficial results.

The success of dietary intervention in the areas of ADHD and Autism suggest

that a greater understanding of biochemical anomalies may also result in

dietary intervention being a useful addition to other treatment procedures for

IS.

The most immediate needs would be to identify whether changes in diet lead to

changes in biochemical profiles and to changes in symptoms, as well as to

explore how dietary essential fatty acid may relate to alterations in body

levels

of trans-9-octadeceoaic (eliadic) acid. It would also be interesting to explore

whether dietary intervention leads to changes in neural responses, as

identified by Uhlig et al. (1997) in relation to dietary changes for children

with

ADHD.

[Guest guest]

J Pediatr Gastroenterol Nutr. 2003 Sep;37(3):262-7. Related Articles, Links

Autoantibodies in mothers of children with neonatal liver disease.

Burch JM, Sokol RJ, Narkewicz MR, Reichlin M, MB, MacKenzie T, Lee LA.

Department of Dermatology, University of Colorado School of Medicine, CO, USA.

OBJECTIVES: Neonatal lupus erythematosus (NLE) is associated with maternal

anti-Ro/La autoantibodies. It is characterized by heart block and/or cutaneous

skin lesions, and occasionally liver disease. This study was performed to

determine whether idiopathic neonatal cholestasis (INC) represents NLE without

its cardiac or cutaneous findings. METHODS: Sera were obtained for autoantibody

analysis from mothers of children with INC (N = 11), biliary atresia (N = 25),

other liver disease excluding viral hepatitis (liver disease control subjects, N

= 14), and healthy children (normal control subjects [NC], N = 22). RESULTS: The

characteristic serologic findings of NLE, high titer antibodies to Ro and/or La,

were absent in mothers from all groups. An unexpected finding was the prevalence

of autoantibodies in mothers of infants with liver disease of any type. The

frequency of maternal antinuclear antibodies at > or = 1:120 dilution was

greater than the estimated frequency in the general population (22% vs. 9%, P =

0.044). The frequency of maternal low titer autoantibodies to 52 kD Ro detected

by ELISA was significantly greater than in the NC group (31% vs. 5%, P = 0.014).

CONCLUSIONS: The majority of cases of INC do not represent NLE. The frequent

presence of autoantibodies in mothers of infants in all neonatal liver disease

groups raises the possibility that maternal serologic autoimmunity is associated

with neonatal liver disease.

PMID: 12960647 [PubMed - in process]

antibodies in mothers of dyslexic children have possible immune system

deficiencies - research page

Immune System Disorders and Learning Disabilities

http://www.bdainternationalconference.org/presentations/thu_s1_a_5.htm

Possible Immune System Deficiencies?

It has been claimed that there may be an immunological basis for learning

problems. Pennington, , Kimberling, Green and Haith (1987) found elevated

levels of antibodies in mothers with dyslexic children, and Lahita (1988) found

mothers with a particular immune system disability had a higher than average

rate of children with learning disorders. Stein and Talcott (1999) and

Galaburda (1997) cite evidence that dyslexics and their families have a greater

than

normal incidence of autoimmune disorders, while Knivsberg's (1997) analysis of

urine samples found more abnormalities in the urine patterns of dyslexics. A

number of other authors have also reported an association between immune

disorders and dyslexia (Armstrong, Seidel, & Swales, 1993; Hugdahl, 1995; Wood &

, 1992). Chronic Fatigue Syndrome has also been associated with a variety

of immune system deficiencies (Dykman, Tone, & Dykman, 1997; Ojo-Amaize,

Conley, & , 1994), as well as dysregulation of immune cell numbers and

cytokine

production (Gupta & Vayevegula, 1991).

The possible association between CFS, visual/ocular problems and immune

system dysfunction was also observed in Study Two. The changes in reading

ability

and response to lens use were associated with indicators of infection as shown

by sore or swollen lymph nodes (Table 2), as well as dysregulation of urinary

metabolites and fatty acid metabolism, which may be indicative of a reaction

to infection (Table 3) (Arao, Soushi, Sato, Moriishi, Audo, Yamada, Padilla,

Uno, Nii, & Kurata 1997; Qavi, Xu, Green, Lusso, Pearson, & Ablashi 1996;

et al., 1999; Singh, Ling, & Yang, 1998).

The high familial incidence of disabilities such as IS (, Foreman, &

Dear, 1996, 2000) suggest that a gene mechanism may influence the probability

of immune system dysfunction. However, while familial gene traits may

influence the probability of familial reading difficulties, the possibility of

familial transfer of infective agents is also a distinct possibility. While

viruses

such as Human Herpes-6 (HHV-6) are not transferred across the placenta,

children usually contract HHV-6 infections in the first couple of years of life

from

other family members. This is important as reactivation of HHV-6 has also been

implicated in the development of CFS (Suhadolnik, Reichenbach, Hitzges,

Sobow, , Henry et al., 1994; Suhadolnik, , O'Brien, Cheney,

Herst,

Reichenbach et al, 1997). This virus may also play some role in alteration of

retinal function. Qavi et al. (1996) showed that HHV-6 was able to infect

corneal epithelial cells, whilst Arao et al. (1997) also showed that HHV-6 was

able to infect retinal pigment epithelial cells. Significantly, Singh et al.

(1998) reported that HHV-6, along with an autoantibody against neuron-axon

filament protein, was increased in patients with autism. Thus the alteration in

visual processing may be associated with a persistent viral infection by HHV-6.

Dietary Intervention as a Treatment Option?

The identification of dysregulated metabolism in people with symptoms of IS

raises the question of dietary manipulation and food supplementation as an

addition to the already established treatments of tinted filters and remedial

support. Dietary intervention for people with dyslexia has been successfully

undertaken by Stordy (1995, 1998) and Makrides et al. (1995) using an essential

fatty acid supplementation. There have been a variety of other investigations

that implicate diet as a potentially important aspect of treatment for people

with learning disabilities. Benton (1997) reported a case study in which a

glyconutritional supplement, given to a child with dyslexia, resulted in claims

of

large improvements in reading and writing activities.

Dietary intervention has also been shown to have a positive effect for people

with ADHD (Boris & Mandel, 1994; , Urbanowicz, Hemsley, Mantilla,

Strobel, Graham, & , 1993; Egger, , Graham, Gumley, & Soothill,

1985;

Egger, Stoller, & McEwen, 1993; Knivesberg, N??dland, Reichelt, & Fosse, 2000;

Uhlig, Merkenschlager, Brandmaier, & Egger, 1997). Uhlig et al. (1997) found a

significant increase in beta brain electrical activity for children with ADHD

following the ingestion of previously identified provoking foods. Knivesberg

et al. (2000) reported on the evaluation of a casein free diet for children

with symptoms of ADHD and additional urinary peptide anomalies. Preliminary data

has identified a significant reduction in peptide levels, as well as

significant improvements in behaviour. et al. (1993) found a significant

worsening in ratings of behaviour and in psychological test performance for

provoking

foods using blinded crossover design. Boris and Mandel (1994), and Egger et

al. (1985) used elimination diets to identify those subjects with ADHD who

responded favourably and then challenged the responders with a variety of foods

in

a placebo-controlled and blinded study. In both cases, there were significant

improvements in behaviour on placebo days compared to challenge days. Egger

et al. (1993) obtained positive results for subjects with ADHD using a food

desensitisation technique and a double-blind, placebo-controlled trial.

There have also been studies of successful dietary intervention for children

with symptoms of autism, and reading problems are more frequent than expected

in families with autism (Le Couteur, 1988). Increased levels of peptides have

been found in urine analyses (Cade, Privette, Fregly, Rowland, Sun, Zele,

Wagemaker, & Edelstein, 2000; Knivsberg, Reichelt, & N??dland, 1999; Knivsberg,

Reichelt, N??dland, & H??ien, 1995; Reichelt, Knivsberg, N??dland, Stensrud, &

Reichelt, 1997), some of which may stem from dietary proteins (Reichelt, Ekrem,

&

, 1990; Shattock, Kennedy, Rowell, & Berney, 1990). When autistic subjects

in the Knivsberg et al. (1995) study were provided with a diet free of gluten

and milk proteins, there was a normalisation of urine patterns and peptide

levels within one year and significant improvements in social, cognitive, and

communicative skills in a four year follow-up. Those subjects who stopped the

diet regressed. Reichelt et al. (1990) also found a normalisation of peptide

patterns and improvement in social skills after one year of a similar dietary

intervention, while Knivsberg et al. (1999) obtained a similar result over two

years of intervention and Cade et al. (2000) after three months of intervention.

Other studies have also found a reduction in symptoms of autism following

dietary changes (Knivsberg, Reichelt, H??ien, & N??dland, 1998; Whiteley,

Rodgers,

Savery, & Shattock, 1999). Preliminary investigations at the University of

Newcastle, Australia, have identified altered urinary amino acid and blood lipid

profiles which can be influenced by dietary supplementation. There were also

increases in long chain fatty acids indicative of poor intracellular processing

of these lipids and supplementation with essential fatty acids could be

beneficial. Analyses of faecal bacteria indicated that important gut bacteria

are

often lacking, and sometimes almost absent, with treatment to normalise this

bacteria having beneficial results.

The success of dietary intervention in the areas of ADHD and Autism suggest

that a greater understanding of biochemical anomalies may also result in

dietary intervention being a useful addition to other treatment procedures for

IS.

The most immediate needs would be to identify whether changes in diet lead to

changes in biochemical profiles and to changes in symptoms, as well as to

explore how dietary essential fatty acid may relate to alterations in body

levels

of trans-9-octadeceoaic (eliadic) acid. It would also be interesting to explore

whether dietary intervention leads to changes in neural responses, as

identified by Uhlig et al. (1997) in relation to dietary changes for children

with

ADHD.

[Guest guest]

Infection and autoimmunity:

Systematic analyses of microbial antigens and infection induced autoimmunity was

presented by U. Sahin (Mainz, Germany).

A number of viral and bacterial infections are associated with antibody mediated

autoimmune diseases. Using the SEREX approach (SErological identification of

Recombinantly EXpressed antigens), they systematically dissected the

autoantibody repertoure of mice after infection with cytopathic or

non-cytopathic viruses. cDNA expression libraries prepared from various organs

were screened using sera harvested from relevant virus-infected mice. The data

presented indicate that virus infections are responsible for a significant

fraction of the autoantibody repertoire and that individual viruses may trigger

specific " autoantibody fingerprint " .

Y. Shoenfeld et al (Tel-Hashomer, Isreal) raised the infection origin of

antiphospholipid syndrome (APS), proved by molecular mimicry between common

bacteria, tetanus toxoid and epitopes on the main antigen beta-2-glycoprotein-I

(ß2GPI ). Previous studies showed presence of anti-bacterial and anti-viral Abs

in the sera of patients with catastrophic APS and in the sera of patients with

clinical manifestations of APS. The group used a peptide phage display library

to identify target epitopes on the ß2GPI molecule for anti-ß2GPI Abs. Using the

protein database they found the amino acid sequences homology (one mis-match) to

a panel of bacteria, viruses and yeasts. Immunization of naïve mice with the

pathogen, purification of anti-ß2GPI peptide Abs and infusion to naïve mice,

reveald that two bacteria and tetanus toxoid were able to induce anti-peptide

Abs which caused experimental APS by passive transfer into naïve mice (JCI

2002).

In the section of Induction of autoantibodies and autoimmune diseases Reeves WH

et al (Gainesville, FL, USA), presented a pristane model of lupus which has a

strong similarity to lupus mice on genetic background (NZB/W/F1 mice). Pristane

(2,6,10,14 tetramethylpenta decane) is one of the hydrocarbon oils derived from

petroleum distillation. The ability of other hydrocarbons to induce a similar

syndrome suggests that unknown chemical properties of these molecules trigger a

pathway leading to autoimmune disease. Since the earliest cells encounter these

materials are cells of the monocyte/ macrophage/dendritic cell lineages, their

data raise the possibility that primary defects at the level of antigen

presenting cell may be capable of stimulating an immunological pathway that

culminates in lupus.

Casiano CA (Loma , CA, USA) referred to the role of apoptotic cleavage of

LEDGF/p75 autoantigen in induction of autoantibodies. LEDGF/p75 lens epithelial

derived growth factor is a nuclear protein which is a target of autoantibodies

in some atopic and chronic inflammatory disorders, as well as novel protein that

promotes mammalian cell growth and confers resistance of cell death induced by a

wide range of environmental stress, including heat shock, oxidative stress and

serum starvation. This group showed that LEDGF/p75 belongs to a subset of

intracellular autoantigens cleaved by proteases (caspase 3,7) during cell death,

in a manner that abrogates its pro-survival function and the cleavage fragment

has a pro-apoptotic activity. In the N terminus the domain PWWP has been

implicated in DNA binding. The protein has two AT-hook motifs that facilitate

interaction with DNA.The researchers propose that the cleavage of LEDGF/p75

during cell death may generate potentially immunostimulatory forms of the

protein that could trigger autoantibody production if presented to autoreactive

lymphocytes under pro-inflammatory environment.

Apoptosis as a mechanism of breaking tolerance to self antigens was raised by

Bachman MP et al (Oklahoma city, Oklahoma, USA). The group hypothesize that

among other mechanisms leading to autoantinodies production is the somatic

mutation in autoantigens, which initiate an autoimmune system in the form of

late apoptotic cell material. They showed that (i) immunization with late

apoptotic cells does not brake tolerance (ii)immunization of non-tolerant mice

with late apoptotic cells initiates an immune response when the cells contain

foreign antigens (e.g. human native or mutant La) (iii) if the homology of the

foreign antigen in the late apoptotic cells is sufficient to break tolerance,

the immune response spreads to other autoantigens (iv) immunization of an

autoantigen initiates an immune response and allows epitope spreading to other

autoantigens, (v) the initial immune response must not necessarily lead to an

autoimmune response to the native form of the antigen (vi) autoimmunity to other

autoantigens can rapidly occur even without a measurable antibody response, and

(vii) the mutant region of the human La antigen is a target of an immune

response in anti-La positive patients. Thus, these data support the important

role of somatic mutation in the LA gene of an autoimmune patient in the

initiation of an autoimmune response, especially if the mutant form of the La

antigen is presented to the immune system in the form of late apoptotic cells.

Pathogenic autoantibodies:

Thioufas et al (Athens, Greece) studied the immunogenicity and antigenicity of

the MBP peptide and the mimicking La/SSB epitope. La 147-154aa peptide when used

for immunization of rabbits could induce epitope spreading. On the contrary the

mimicking epitope MBP139-146aa could only induce the production of antibodies

against itself and the homologousLa/SSB peptide. A significant proportion of

human sera reacted with both peptides. Thus, despite the fact that these two

peptides present molecular similarity, they induce different immune responses.

Van Venrooij WJ et al (Nijmegen, The Netherlands) showed the association between

anti-citrulline antibodies and citrullinating enzymes in RA. Antibodies directed

against citrullinated proteins are extremely specific for RA (>98% specific,

>75% sensitive). Citrulline is amino acid that is not incorporated into proteins

during protein synthesis. It can be generated by posttranslational modification

of arginine residues by PAD (peptidylarginine deiminase) enzymes (of which 4

isoforms exist in human). In the current presentation the group suggest that PAD

type 2 is involved in the citrullination of synovial proteins during

inflammation.

The anti-CCP Abs were found to be extremely specific for RA. The senditivity of

the anti-CCP test is comparable to that of the RF test. Anti-CCP Abs are present

very early in the disease and have prognodtic value because they are

predominantly present in patients with erosive disease.

Evidence for immunity to type II collagen in the pathogenesis of rheumatoid

arthritis: high frequency of antibodies to collagen fragment CB10 was documented

by Rowley MJ (Melbourne, Australia). Antibodies to type II collagen occur in

serum and synovial fluid from patients with rheumatoid arthritis. They may occur

very early in the disease, and are associated with HLA susceptibility markers,

but in most studies the frequencies of such antibodies in serum are low. The aim

of this study was to determine the frequency of antibodies using a sensitive

ELISA assay based on the use of the CB10 polypeptide derived by digestion of

collagen II with cyanogen bromide. Levels of antibodies to CB10 were highest in

patients with early rheumatoid arthritis and decreased with increasing duration

of disease. There was no correlation between antibodies to CB10 and the presence

of rheumatoid factor. The use of CB10 as antigen increased the sensitivity of

collagen antibody assays without apparent loss of specificity. These results

indicate that immunity to collagen is more common than is known to realized in

patients with RA, and may play a role in pathogenesis.

Autoantibodies directed to certain ion channels were presented by Beth Lang

((Oxford, UK) in three disorders of the peripheral nervous system. The rise and

fall of the antibody titers can be used to monitor treatment . The detection of

anti-VGCC antibodies (voltage gate calcium channel) in Lambert Eaton Myasthemia

Syndrome (LEMS) patients with a history of smoking will intensify the hunt for

an underlying Small Cell Lung Carcinoma (SCLC). Other antibodies that activate

at the neuromuscular junction have been described (anti-ganglioside). Autonomic

dysfunction has been reported in LEMS, anti-VGCC cross react with channels

expressed in the autonomic nervous system. Anti-VGKC antibodies (voltage gate

potassium channel) in acquired neuromyotonia have shown to be in a strong

correlation with the pathogenesis of the disease. The importance of anti-ion

channels in CNS disorders on an autoimmune background was discussed.

Reactivity of antibodies against human muscle-beta-enolase with bacterial outer

membrane proteins was presented by Witkowska D (Wroclaw, Poland). Molecular

mimicry between enterobacteriol outer-membrane proteins and human muscle enolase

was presented. This glycolytic enzyme may play a role in progress of autoimmune

disorders.This is also important for the preparation of antibacterial vaccines.

Molecular dissection of the Goodpasture epitope. Was performed by the group of

Wieslander J et al (Virginia, USA). By constructing recombinant chimeric

molecules between the non-reactive-alpha 1 chain and the reactive alpha 3 chain

they were able to show that all patients have antibodies to the first

N-terminal-third of the NC1 domain. Furthermore, a variety of recombinant NC1

domains were constructed by replacing single amino acid residues of alpha3 with

the corresponding amino acids from the alpha 1 chain. The studies for the first

time define a conformational epitope that is both the target of pathogenic human

antibodies and can induce disease when injected intoanimals.They are confident

that the restriction of the epitope is of a significant importance for the

understanding of the etiology of the disease and is crucial for the development

of a better diagnostic tools as well as specific therapy.

Anti-prothrombin subpopulations of autoantibodies were characterized by Koike T

(Saporo, Japan). T. Koike showed the association of the anti-prothrombin

antibodies which bind prothrombin on a phosphatidylserine matrix in the presence

of calcium ions, with thrombosis rather than with pregnancy loss. The mechanism

of activity was discussed.

Autoantibodies associated with reproductive failure were summarized by Blank et

al (Tel-Hadhomet , Israel). Autoimmune factors are involved in some of the cases

of reproductive failure. These factors entail several autoantibodies, mainly in

patients having SLE or the antiphospholipid syndrome. These autoantibodies

include mainly antibodies directed to DNA Ro/La, phospholipids such as

cardiolipin, phosphatidylserine, phosphatidylethanolamine, or phospholipids

binding glycoproteins such as ß2glycoprotein-I, annexin V, prothrombin,

including the subpopulation of complement fixing antiphospholipid antibodies.

There are also some other autoantibodies directed to laminin-I, thromboplastin,

mitochondrial antibodies of the M5 type, corpus luteum, prolactin, poly

(ADP-ribose), thyroglobulin and more, which were also found in autoimmune

conditions. Moreover, the presence of additional autoantibodies such as

anti-actin, anti-enolase, anti-cubilin and others, needs further investigation

to support a firm association to reproductive failure. (high incidence in

mothers

of autistic children)

Autoantibodies in risk groups for autoimmune diseases was presented by Conrad K

(Dresden, Germany). Silica exposure has been regarded a sone possible factor in

the mosaic of the pathogenesis of several systemic autoimmune diseases,

including systemic sclerosis (SSc), SLE, rheumatoid arthritis (RA) and ANCA

associated vasculitidies. High frequency of SSc/SLE autoantibodies was detected

in uranium miner associated with clinical manifestations, relationship between

occupationally factors and autoimmune disease was analyzed.

Fascinating work was presented by Meroni PL (Milan, Italy), characterizing the

role of anti-fibroblast antibodies (AFA) in systemic sclerosis. Meroni showed

that upon binding to the cell surface, AFA penetrate the cells via Fc?R

involvement and induce fibroblast activation leading to the enhanced production

of pro-inflammatory cytokines (IL-6) and upregulation of ICAM-I. AFA-positive

SSc IgG induce a proadhesive phenotype in fibroblasts. Fibroblasts showing

enhanced collagen synthesis upon close contact with mononuclear cells. He

speculated that these events may contribute in triggering or maintaining the

recruitment of inflammatory cells to tissues undergoing fibrosis and indirectly

or indirectly promote a pro-fibrotic phenotype in fibroblasts.

Hiepe F (Berlin, Germany) showed the pathogenic role of anti-Ro/SSA

autoantiboides in cutaneous manifestations of lupus. The TNFa was found to

induce upregulation of 52kD Ro/SSA autoantigen expression in human keratinocytes

mediated via TNFa Receptor I (TNF-RI). This upregulation was reduced by the

anti-TNF-RI antibody. The expression level of 52kD Ro/SSA mRNA was 25% less in

the presence of the neutralizing antibody. Similar to mRNA expression,

52kDRo/SSA protein upregulation by TNFa was neutralized by the anti-TNF-RI

antibody. The results suggest that TNF-RI receptor is involved in the TNFa

mediated upregulation of 52kD Ro/SSA autoantigen in keratinocytes.

The audience left the meeting with diverse new ideas both on autoantigens and on

the novel diagnostic systems being introduced nowadays. It has been decided that

the following autoantibodies meetings in Dresden will alternate in years with

the International Congresses of Autoimmunity.

To top

antibodies in mothers of dyslexic children have possible immune system

deficiencies - research page

Immune System Disorders and Learning Disabilities

http://www.bdainternationalconference.org/presentations/thu_s1_a_5.htm

Possible Immune System Deficiencies?

It has been claimed that there may be an immunological basis for learning

problems. Pennington, , Kimberling, Green and Haith (1987) found elevated

levels of antibodies in mothers with dyslexic children, and Lahita (1988) found

mothers with a particular immune system disability had a higher than average

rate of children with learning disorders. Stein and Talcott (1999) and

Galaburda (1997) cite evidence that dyslexics and their families have a greater

than

normal incidence of autoimmune disorders, while Knivsberg's (1997) analysis of

urine samples found more abnormalities in the urine patterns of dyslexics. A

number of other authors have also reported an association between immune

disorders and dyslexia (Armstrong, Seidel, & Swales, 1993; Hugdahl, 1995; Wood &

, 1992). Chronic Fatigue Syndrome has also been associated with a variety

of immune system deficiencies (Dykman, Tone, & Dykman, 1997; Ojo-Amaize,

Conley, & , 1994), as well as dysregulation of immune cell numbers and

cytokine

production (Gupta & Vayevegula, 1991).

The possible association between CFS, visual/ocular problems and immune

system dysfunction was also observed in Study Two. The changes in reading

ability

and response to lens use were associated with indicators of infection as shown

by sore or swollen lymph nodes (Table 2), as well as dysregulation of urinary

metabolites and fatty acid metabolism, which may be indicative of a reaction

to infection (Table 3) (Arao, Soushi, Sato, Moriishi, Audo, Yamada, Padilla,

Uno, Nii, & Kurata 1997; Qavi, Xu, Green, Lusso, Pearson, & Ablashi 1996;

et al., 1999; Singh, Ling, & Yang, 1998).

The high familial incidence of disabilities such as IS (, Foreman, &

Dear, 1996, 2000) suggest that a gene mechanism may influence the probability

of immune system dysfunction. However, while familial gene traits may

influence the probability of familial reading difficulties, the possibility of

familial transfer of infective agents is also a distinct possibility. While

viruses

such as Human Herpes-6 (HHV-6) are not transferred across the placenta,

children usually contract HHV-6 infections in the first couple of years of life

from

other family members. This is important as reactivation of HHV-6 has also been

implicated in the development of CFS (Suhadolnik, Reichenbach, Hitzges,

Sobow, , Henry et al., 1994; Suhadolnik, , O'Brien, Cheney,

Herst,

Reichenbach et al, 1997). This virus may also play some role in alteration of

retinal function. Qavi et al. (1996) showed that HHV-6 was able to infect

corneal epithelial cells, whilst Arao et al. (1997) also showed that HHV-6 was

able to infect retinal pigment epithelial cells. Significantly, Singh et al.

(1998) reported that HHV-6, along with an autoantibody against neuron-axon

filament protein, was increased in patients with autism. Thus the alteration in

visual processing may be associated with a persistent viral infection by HHV-6.

Dietary Intervention as a Treatment Option?

The identification of dysregulated metabolism in people with symptoms of IS

raises the question of dietary manipulation and food supplementation as an

addition to the already established treatments of tinted filters and remedial

support. Dietary intervention for people with dyslexia has been successfully

undertaken by Stordy (1995, 1998) and Makrides et al. (1995) using an essential

fatty acid supplementation. There have been a variety of other investigations

that implicate diet as a potentially important aspect of treatment for people

with learning disabilities. Benton (1997) reported a case study in which a

glyconutritional supplement, given to a child with dyslexia, resulted in claims

of

large improvements in reading and writing activities.

Dietary intervention has also been shown to have a positive effect for people

with ADHD (Boris & Mandel, 1994; , Urbanowicz, Hemsley, Mantilla,

Strobel, Graham, & , 1993; Egger, , Graham, Gumley, & Soothill,

1985;

Egger, Stoller, & McEwen, 1993; Knivesberg, N??dland, Reichelt, & Fosse, 2000;

Uhlig, Merkenschlager, Brandmaier, & Egger, 1997). Uhlig et al. (1997) found a

significant increase in beta brain electrical activity for children with ADHD

following the ingestion of previously identified provoking foods. Knivesberg

et al. (2000) reported on the evaluation of a casein free diet for children

with symptoms of ADHD and additional urinary peptide anomalies. Preliminary data

has identified a significant reduction in peptide levels, as well as

significant improvements in behaviour. et al. (1993) found a significant

worsening in ratings of behaviour and in psychological test performance for

provoking

foods using blinded crossover design. Boris and Mandel (1994), and Egger et

al. (1985) used elimination diets to identify those subjects with ADHD who

responded favourably and then challenged the responders with a variety of foods

in

a placebo-controlled and blinded study. In both cases, there were significant

improvements in behaviour on placebo days compared to challenge days. Egger

et al. (1993) obtained positive results for subjects with ADHD using a food

desensitisation technique and a double-blind, placebo-controlled trial.

There have also been studies of successful dietary intervention for children

with symptoms of autism, and reading problems are more frequent than expected

in families with autism (Le Couteur, 1988). Increased levels of peptides have

been found in urine analyses (Cade, Privette, Fregly, Rowland, Sun, Zele,

Wagemaker, & Edelstein, 2000; Knivsberg, Reichelt, & N??dland, 1999; Knivsberg,

Reichelt, N??dland, & H??ien, 1995; Reichelt, Knivsberg, N??dland, Stensrud, &

Reichelt, 1997), some of which may stem from dietary proteins (Reichelt, Ekrem,

&

, 1990; Shattock, Kennedy, Rowell, & Berney, 1990). When autistic subjects

in the Knivsberg et al. (1995) study were provided with a diet free of gluten

and milk proteins, there was a normalisation of urine patterns and peptide

levels within one year and significant improvements in social, cognitive, and

communicative skills in a four year follow-up. Those subjects who stopped the

diet regressed. Reichelt et al. (1990) also found a normalisation of peptide

patterns and improvement in social skills after one year of a similar dietary

intervention, while Knivsberg et al. (1999) obtained a similar result over two

years of intervention and Cade et al. (2000) after three months of intervention.

Other studies have also found a reduction in symptoms of autism following

dietary changes (Knivsberg, Reichelt, H??ien, & N??dland, 1998; Whiteley,

Rodgers,

Savery, & Shattock, 1999). Preliminary investigations at the University of

Newcastle, Australia, have identified altered urinary amino acid and blood lipid

profiles which can be influenced by dietary supplementation. There were also

increases in long chain fatty acids indicative of poor intracellular processing

of these lipids and supplementation with essential fatty acids could be

beneficial. Analyses of faecal bacteria indicated that important gut bacteria

are

often lacking, and sometimes almost absent, with treatment to normalise this

bacteria having beneficial results.

The success of dietary intervention in the areas of ADHD and Autism suggest

that a greater understanding of biochemical anomalies may also result in

dietary intervention being a useful addition to other treatment procedures for

IS.

The most immediate needs would be to identify whether changes in diet lead to

changes in biochemical profiles and to changes in symptoms, as well as to

explore how dietary essential fatty acid may relate to alterations in body

levels

of trans-9-octadeceoaic (eliadic) acid. It would also be interesting to explore

whether dietary intervention leads to changes in neural responses, as

identified by Uhlig et al. (1997) in relation to dietary changes for children

with

ADHD.

[Guest guest]

(SJORJAN SYNDROME)

Editor M. Cutolo et al (Padova, Italy) stressed the importance of oestrogens as

enhancers of the immune response and androgens as natural immunosuppressors.

Anti-Ro antibodies recognised the Ro complex, that environmental as well as

oestrogens seem to translocate it to nucleocytoplasmic and membrane sites where

it is not normally found, thereby leading to the development of autoimmunity.

They suggested that a link between the effects of oestrogens/androgens levels

and oestrogens receptor/androgens receptor co-distribution on and/or with Ro/La

autoantigens might be implicated in the high frequency of anti Ro induction in

females. However, the contribution of the androgens and oestrogens to SS remains

controversial.

In the poster session, B.D. Sullivan et al (Boston, MA) demonstrated that

androgen deficiency is associated with significant alterations in the fatty acid

profiles of neutral and polar lipid fractions in human meibomian gland

secretions. These changes may contribute to the tear film instability and

evaporative dry eye found in various androgen-deficient states, such as SS. On

the other hand, M.T. Brennan et al (Philadelphia, PA) did not find correlation

between disease activity and oestrogen levels. Even more, they found higher

levels of disease activity associated with higher levels of androgen sex

hormones.

In the poster session, G. Colombo et al (Brescia, Italy) reported that mothers

with congenital complete heart block presented a strong genetic similarity to

mothers who had SS, except for HLA class I phenotype. The combined presence of

HLA-DRB1*03011 and anti-52-kd Ro antibodies conveyed the highest risk of giving

birth to an affected child. A. I. Bolstad (Bergen, Norway) studied HLA markers

and clinical characteristics in Caucasians with primary SS. His group found that

the HLA markers were primary associated with ant-Ro/La response. Amino acid

DQa-34E was protective and DQb-26L was not associated with pSS.

antibodies in mothers of dyslexic children have possible immune system

deficiencies - research page

Immune System Disorders and Learning Disabilities

http://www.bdainternationalconference.org/presentations/thu_s1_a_5.htm

Possible Immune System Deficiencies?

It has been claimed that there may be an immunological basis for learning

problems. Pennington, , Kimberling, Green and Haith (1987) found elevated

levels of antibodies in mothers with dyslexic children, and Lahita (1988) found

mothers with a particular immune system disability had a higher than average

rate of children with learning disorders. Stein and Talcott (1999) and

Galaburda (1997) cite evidence that dyslexics and their families have a greater

than

normal incidence of autoimmune disorders, while Knivsberg's (1997) analysis of

urine samples found more abnormalities in the urine patterns of dyslexics. A

number of other authors have also reported an association between immune

disorders and dyslexia (Armstrong, Seidel, & Swales, 1993; Hugdahl, 1995; Wood &

, 1992). Chronic Fatigue Syndrome has also been associated with a variety

of immune system deficiencies (Dykman, Tone, & Dykman, 1997; Ojo-Amaize,

Conley, & , 1994), as well as dysregulation of immune cell numbers and

cytokine

production (Gupta & Vayevegula, 1991).

The possible association between CFS, visual/ocular problems and immune

system dysfunction was also observed in Study Two. The changes in reading

ability

and response to lens use were associated with indicators of infection as shown

by sore or swollen lymph nodes (Table 2), as well as dysregulation of urinary

metabolites and fatty acid metabolism, which may be indicative of a reaction

to infection (Table 3) (Arao, Soushi, Sato, Moriishi, Audo, Yamada, Padilla,

Uno, Nii, & Kurata 1997; Qavi, Xu, Green, Lusso, Pearson, & Ablashi 1996;

et al., 1999; Singh, Ling, & Yang, 1998).

The high familial incidence of disabilities such as IS (, Foreman, &

Dear, 1996, 2000) suggest that a gene mechanism may influence the probability

of immune system dysfunction. However, while familial gene traits may

influence the probability of familial reading difficulties, the possibility of

familial transfer of infective agents is also a distinct possibility. While

viruses

such as Human Herpes-6 (HHV-6) are not transferred across the placenta,

children usually contract HHV-6 infections in the first couple of years of life

from

other family members. This is important as reactivation of HHV-6 has also been

implicated in the development of CFS (Suhadolnik, Reichenbach, Hitzges,

Sobow, , Henry et al., 1994; Suhadolnik, , O'Brien, Cheney,

Herst,

Reichenbach et al, 1997). This virus may also play some role in alteration of

retinal function. Qavi et al. (1996) showed that HHV-6 was able to infect

corneal epithelial cells, whilst Arao et al. (1997) also showed that HHV-6 was

able to infect retinal pigment epithelial cells. Significantly, Singh et al.

(1998) reported that HHV-6, along with an autoantibody against neuron-axon

filament protein, was increased in patients with autism. Thus the alteration in

visual processing may be associated with a persistent viral infection by HHV-6.

Dietary Intervention as a Treatment Option?

The identification of dysregulated metabolism in people with symptoms of IS

raises the question of dietary manipulation and food supplementation as an

addition to the already established treatments of tinted filters and remedial

support. Dietary intervention for people with dyslexia has been successfully

undertaken by Stordy (1995, 1998) and Makrides et al. (1995) using an essential

fatty acid supplementation. There have been a variety of other investigations

that implicate diet as a potentially important aspect of treatment for people

with learning disabilities. Benton (1997) reported a case study in which a

glyconutritional supplement, given to a child with dyslexia, resulted in claims

of

large improvements in reading and writing activities.

Dietary intervention has also been shown to have a positive effect for people

with ADHD (Boris & Mandel, 1994; , Urbanowicz, Hemsley, Mantilla,

Strobel, Graham, & , 1993; Egger, , Graham, Gumley, & Soothill,

1985;

Egger, Stoller, & McEwen, 1993; Knivesberg, N??dland, Reichelt, & Fosse, 2000;

Uhlig, Merkenschlager, Brandmaier, & Egger, 1997). Uhlig et al. (1997) found a

significant increase in beta brain electrical activity for children with ADHD

following the ingestion of previously identified provoking foods. Knivesberg

et al. (2000) reported on the evaluation of a casein free diet for children

with symptoms of ADHD and additional urinary peptide anomalies. Preliminary data

has identified a significant reduction in peptide levels, as well as

significant improvements in behaviour. et al. (1993) found a significant

worsening in ratings of behaviour and in psychological test performance for

provoking

foods using blinded crossover design. Boris and Mandel (1994), and Egger et

al. (1985) used elimination diets to identify those subjects with ADHD who

responded favourably and then challenged the responders with a variety of foods

in

a placebo-controlled and blinded study. In both cases, there were significant

improvements in behaviour on placebo days compared to challenge days. Egger

et al. (1993) obtained positive results for subjects with ADHD using a food

desensitisation technique and a double-blind, placebo-controlled trial.

There have also been studies of successful dietary intervention for children

with symptoms of autism, and reading problems are more frequent than expected

in families with autism (Le Couteur, 1988). Increased levels of peptides have

been found in urine analyses (Cade, Privette, Fregly, Rowland, Sun, Zele,

Wagemaker, & Edelstein, 2000; Knivsberg, Reichelt, & N??dland, 1999; Knivsberg,

Reichelt, N??dland, & H??ien, 1995; Reichelt, Knivsberg, N??dland, Stensrud, &

Reichelt, 1997), some of which may stem from dietary proteins (Reichelt, Ekrem,

&

, 1990; Shattock, Kennedy, Rowell, & Berney, 1990). When autistic subjects

in the Knivsberg et al. (1995) study were provided with a diet free of gluten

and milk proteins, there was a normalisation of urine patterns and peptide

levels within one year and significant improvements in social, cognitive, and

communicative skills in a four year follow-up. Those subjects who stopped the

diet regressed. Reichelt et al. (1990) also found a normalisation of peptide

patterns and improvement in social skills after one year of a similar dietary

intervention, while Knivsberg et al. (1999) obtained a similar result over two

years of intervention and Cade et al. (2000) after three months of intervention.

Other studies have also found a reduction in symptoms of autism following

dietary changes (Knivsberg, Reichelt, H??ien, & N??dland, 1998; Whiteley,

Rodgers,

Savery, & Shattock, 1999). Preliminary investigations at the University of

Newcastle, Australia, have identified altered urinary amino acid and blood lipid

profiles which can be influenced by dietary supplementation. There were also

increases in long chain fatty acids indicative of poor intracellular processing

of these lipids and supplementation with essential fatty acids could be

beneficial. Analyses of faecal bacteria indicated that important gut bacteria

are

often lacking, and sometimes almost absent, with treatment to normalise this

bacteria having beneficial results.

The success of dietary intervention in the areas of ADHD and Autism suggest

that a greater understanding of biochemical anomalies may also result in

dietary intervention being a useful addition to other treatment procedures for

IS.

The most immediate needs would be to identify whether changes in diet lead to

changes in biochemical profiles and to changes in symptoms, as well as to

explore how dietary essential fatty acid may relate to alterations in body

levels

of trans-9-octadeceoaic (eliadic) acid. It would also be interesting to explore

whether dietary intervention leads to changes in neural responses, as

identified by Uhlig et al. (1997) in relation to dietary changes for children

with

ADHD.

[Guest guest]

Persistence of IgG anti-Ro/La in Breast Milk: Implications for Neonatal Lupus

The presence of FcRn receptors on intestinal epithelium suggests that transfer

of IgG across the human gut is a source of maternal antibodies to the breast-fed

infant. Miranda et al (USA) sought to determine whether antibodies to 48La,

52To, and/or 60Ro are present in breast milk and the frequency of breast-feeding

among mothers enrolled in the Registry for Neonatal Lupus.

Breast milk reflects the maternal serum and contains antibodies of all isotypes

to each component of Ro/La, which can persist up to 1 year. While breast-feeding

did not invariably associate with neonatal lupus, mothers should be cautioned

regarding the possibility of antibody transfer, particularly in the presence of

a prolonged neonatal rash or postpartum myocarditis/cardiomyopathy.

antibodies in mothers of dyslexic children have possible immune system

deficiencies - research page

Immune System Disorders and Learning Disabilities

http://www.bdainternationalconference.org/presentations/thu_s1_a_5.htm

Possible Immune System Deficiencies?

It has been claimed that there may be an immunological basis for learning

problems. Pennington, , Kimberling, Green and Haith (1987) found elevated

levels of antibodies in mothers with dyslexic children, and Lahita (1988) found

mothers with a particular immune system disability had a higher than average

rate of children with learning disorders. Stein and Talcott (1999) and

Galaburda (1997) cite evidence that dyslexics and their families have a greater

than

normal incidence of autoimmune disorders, while Knivsberg's (1997) analysis of

urine samples found more abnormalities in the urine patterns of dyslexics. A

number of other authors have also reported an association between immune

disorders and dyslexia (Armstrong, Seidel, & Swales, 1993; Hugdahl, 1995; Wood &

, 1992). Chronic Fatigue Syndrome has also been associated with a variety

of immune system deficiencies (Dykman, Tone, & Dykman, 1997; Ojo-Amaize,

Conley, & , 1994), as well as dysregulation of immune cell numbers and

cytokine

production (Gupta & Vayevegula, 1991).

The possible association between CFS, visual/ocular problems and immune

system dysfunction was also observed in Study Two. The changes in reading

ability

and response to lens use were associated with indicators of infection as shown

by sore or swollen lymph nodes (Table 2), as well as dysregulation of urinary

metabolites and fatty acid metabolism, which may be indicative of a reaction

to infection (Table 3) (Arao, Soushi, Sato, Moriishi, Audo, Yamada, Padilla,

Uno, Nii, & Kurata 1997; Qavi, Xu, Green, Lusso, Pearson, & Ablashi 1996;

et al., 1999; Singh, Ling, & Yang, 1998).

The high familial incidence of disabilities such as IS (, Foreman, &

Dear, 1996, 2000) suggest that a gene mechanism may influence the probability

of immune system dysfunction. However, while familial gene traits may

influence the probability of familial reading difficulties, the possibility of

familial transfer of infective agents is also a distinct possibility. While

viruses

such as Human Herpes-6 (HHV-6) are not transferred across the placenta,

children usually contract HHV-6 infections in the first couple of years of life

from

other family members. This is important as reactivation of HHV-6 has also been

implicated in the development of CFS (Suhadolnik, Reichenbach, Hitzges,

Sobow, , Henry et al., 1994; Suhadolnik, , O'Brien, Cheney,

Herst,

Reichenbach et al, 1997). This virus may also play some role in alteration of

retinal function. Qavi et al. (1996) showed that HHV-6 was able to infect

corneal epithelial cells, whilst Arao et al. (1997) also showed that HHV-6 was

able to infect retinal pigment epithelial cells. Significantly, Singh et al.

(1998) reported that HHV-6, along with an autoantibody against neuron-axon

filament protein, was increased in patients with autism. Thus the alteration in

visual processing may be associated with a persistent viral infection by HHV-6.

Dietary Intervention as a Treatment Option?

The identification of dysregulated metabolism in people with symptoms of IS

raises the question of dietary manipulation and food supplementation as an

addition to the already established treatments of tinted filters and remedial

support. Dietary intervention for people with dyslexia has been successfully

undertaken by Stordy (1995, 1998) and Makrides et al. (1995) using an essential

fatty acid supplementation. There have been a variety of other investigations

that implicate diet as a potentially important aspect of treatment for people

with learning disabilities. Benton (1997) reported a case study in which a

glyconutritional supplement, given to a child with dyslexia, resulted in claims

of

large improvements in reading and writing activities.

Dietary intervention has also been shown to have a positive effect for people

with ADHD (Boris & Mandel, 1994; , Urbanowicz, Hemsley, Mantilla,

Strobel, Graham, & , 1993; Egger, , Graham, Gumley, & Soothill,

1985;

Egger, Stoller, & McEwen, 1993; Knivesberg, N??dland, Reichelt, & Fosse, 2000;

Uhlig, Merkenschlager, Brandmaier, & Egger, 1997). Uhlig et al. (1997) found a

significant increase in beta brain electrical activity for children with ADHD

following the ingestion of previously identified provoking foods. Knivesberg

et al. (2000) reported on the evaluation of a casein free diet for children

with symptoms of ADHD and additional urinary peptide anomalies. Preliminary data

has identified a significant reduction in peptide levels, as well as

significant improvements in behaviour. et al. (1993) found a significant

worsening in ratings of behaviour and in psychological test performance for

provoking

foods using blinded crossover design. Boris and Mandel (1994), and Egger et

al. (1985) used elimination diets to identify those subjects with ADHD who

responded favourably and then challenged the responders with a variety of foods

in

a placebo-controlled and blinded study. In both cases, there were significant

improvements in behaviour on placebo days compared to challenge days. Egger

et al. (1993) obtained positive results for subjects with ADHD using a food

desensitisation technique and a double-blind, placebo-controlled trial.

There have also been studies of successful dietary intervention for children

with symptoms of autism, and reading problems are more frequent than expected

in families with autism (Le Couteur, 1988). Increased levels of peptides have

been found in urine analyses (Cade, Privette, Fregly, Rowland, Sun, Zele,

Wagemaker, & Edelstein, 2000; Knivsberg, Reichelt, & N??dland, 1999; Knivsberg,

Reichelt, N??dland, & H??ien, 1995; Reichelt, Knivsberg, N??dland, Stensrud, &

Reichelt, 1997), some of which may stem from dietary proteins (Reichelt, Ekrem,

&

, 1990; Shattock, Kennedy, Rowell, & Berney, 1990). When autistic subjects

in the Knivsberg et al. (1995) study were provided with a diet free of gluten

and milk proteins, there was a normalisation of urine patterns and peptide

levels within one year and significant improvements in social, cognitive, and

communicative skills in a four year follow-up. Those subjects who stopped the

diet regressed. Reichelt et al. (1990) also found a normalisation of peptide

patterns and improvement in social skills after one year of a similar dietary

intervention, while Knivsberg et al. (1999) obtained a similar result over two

years of intervention and Cade et al. (2000) after three months of intervention.

Other studies have also found a reduction in symptoms of autism following

dietary changes (Knivsberg, Reichelt, H??ien, & N??dland, 1998; Whiteley,

Rodgers,

Savery, & Shattock, 1999). Preliminary investigations at the University of

Newcastle, Australia, have identified altered urinary amino acid and blood lipid

profiles which can be influenced by dietary supplementation. There were also

increases in long chain fatty acids indicative of poor intracellular processing

of these lipids and supplementation with essential fatty acids could be

beneficial. Analyses of faecal bacteria indicated that important gut bacteria

are

often lacking, and sometimes almost absent, with treatment to normalise this

bacteria having beneficial results.

The success of dietary intervention in the areas of ADHD and Autism suggest

that a greater understanding of biochemical anomalies may also result in

dietary intervention being a useful addition to other treatment procedures for

IS.

The most immediate needs would be to identify whether changes in diet lead to

changes in biochemical profiles and to changes in symptoms, as well as to

explore how dietary essential fatty acid may relate to alterations in body

levels

of trans-9-octadeceoaic (eliadic) acid. It would also be interesting to explore

whether dietary intervention leads to changes in neural responses, as

identified by Uhlig et al. (1997) in relation to dietary changes for children

with

ADHD.