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1-A consistent pattern of minor immunodeficiency and subtle enteropathy in

children with multiple food allergy

2-Reduced transforming growth factor-beta1-producing T cells in the duodenal

mucosa of children with food allergy

3-Cow's milk allergy: a new understanding from immunology.

4-Study on immunological confirmation of allergy in children with

hypoimmunoglobulinemia]

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J Pediatr. 2003 Jul;143(1):39-47. Related Articles, Links

A consistent pattern of minor immunodeficiency and subtle enteropathy in

children with multiple food allergy.

Latcham F, Merino F, Lang A, Garvey J, Thomson MA, - JA, Davies

SE, AD, Murch SH.

Centre for Paediatric Gastroenterology and Department of Dietetics and

Histopathology, Royal Free and University College School of Medicine,

London, United Kingdom.

OBJECTIVE: Although immunoglobulin (Ig)E-mediated allergies are readily

identifiable, non-IgE-mediated allergies present more diagnostic difficulty.

We performed a formal retrospective analysis to determine whether there is a

recognizable clinical pattern in children.

METHODS: We studied 121 children (mean age, 17.3 months) with multiple food

allergies who were recruited on the basis of adequate immunological

assessment by using case notes and parental questionnaire.

RESULTS: Group 1 (n=44) had rapid reactions to dietary antigens, of whom 41

also showed delayed reactions. Group 2 (n=77) had delayed reactions only.

Mean IgE was increased in group 1 but both groups otherwise shared a pattern

of increased IgG1, decreased IgG2/4, and low-normal IgA.

Lymphocyte subsets were skewed, with an increased percentage of CD4 and CD19

and decreased CD8 and natural killer cells. Gastroesophageal reflux,

esophagitis, subtle enteropathy, and constipation were frequent in both

groups. Of 55 exclusively breast-fed infants, 44 sensitized before weaning.

Twenty-one of the mothers suffered from autoimmunity.

CONCLUSIONS: There appears to be a recognizable pattern of immune deviation

and minor enteropathy in children with multiple food allergy, irrespective

of the speed of reactions. Disturbed gut motility is particularly common, as

is a maternal history of autoimmunity.

PMID: 12915822 [PubMed - in process]

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Eur J Immunol. 2003 Aug;33(8):2307-15. Related Articles, Links

Reduced transforming growth factor-beta1-producing T cells in the duodenal

mucosa of children with food allergy.

-Machado MA, Ashwood P, Thomson MA, Latcham F, Sim R, - JA,

Murch SH.

Centre for Paediatric Gastroenterology, Royal Free and University College

School of Medicine, London, GB.

Infant food allergies are increasing, and many breast-fed infants now

sensitize to maternally-ingested antigens. As low-dose oral tolerance

requires generation of suppressor lymphocytes producing TGF-beta1 (Th3

cells), we studied these cells in duodenal biopsies after diagnostic

endoscopy. Spontaneous production of Th1, Th2 and Th3 cytokines by duodenal

lymphocytes was studied using flow cytometry in 20 children with no eventual

clinico-pathological diagnosis (controls), 30 children with multiple food

allergy, nine with celiac disease and six with inflammatory enteropathies.

Immunohistochemistry and in situ hybridization were used to localize

TGF-beta1 protein and mRNA in matched biopsies.

We found no significant Th1/Th2 skewing amongst mucosal lymphocytes in

allergic children compared to controls, although celiac and inflammatory

enteropathy patients showed increased Th1 responses.

By contrast, the allergic children showed reduction of TGF-beta1(+)

lymphocytes in both epithelial and lamina propria compartments. Reduction of

TGF-beta1 expression was also seen in mononuclear cells and epithelium in

food allergy by immunohistochemistry and in situ hybridization.

The dominant mucosal abnormality in food allergic children was, thus, not

Th2 deviation but impaired generation of Th3 cells. As generation of these

cells requires innate immune response to enteric bacteria, we suggest that

changing infectious exposures may inhibit primary establishment of basic

oral tolerance mechanisms.

PMID: 12884306 [PubMed - in process]

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Ann Allergy Asthma Immunol. 2003 Jun;90(6 Suppl 3):81-3. Related Articles,

Links

Cow's milk allergy: a new understanding from immunology.

- J.

University Department of Paediatric Gastroenterology, Royal Free Campus,

Royal Free and University College Medical School, University College,

London, United Kingdom. johnwalker_smith@...

BACKGROUND: Because of the high prevalence of cow's milk allergy as one of

the most frequent clinical presentations of food allergy in infancy and

early childhood, it is important to define the condition accurately. Allergy

must be distinguished from the broader term food intolerance, which may be

defined as a reproducible adverse reaction to the ingestion of a food or to

any of its components, ie, proteins, carbohydrates, fats, and additives, and

which includes toxic, metabolic, and allergic reactions. By contrast, food

allergy may be defined as an adverse clinical reaction to a specific food

component and that is immunologically mediated.

The rapid increase in knowledge resulting from research in immunology in

recent years has not only led to a better understanding of the basis for

cow's milk allergy in infancy, but has also yielded considerable promise for

improved diagnosis and management of the condition.

OBJECTIVE: To review recent developments in immunology which demonstrate how

they may lead to a better understanding of the clinical spectrum of cow's

milk allergy in infants and children. DATA SOURCES: English language

articles were selected from PubMed and selected abstracts that would have

immediate, practical clinical implications. The review focuses on themes

related to gastro-enterology, focusing upon the esophagus and small

intestine.

RESULTS: In cow's milk-sensitive esophagitis, there is dense infiltrate of

eosinophils and increased T cell activation with upregulation of the

chemokine eotaxin. In cow's milk-sensitive enteropathy, there is T cell

activation, and it often results as a sequela of gastro-enteritis.

Changing patterns in recent years suggests that sensitization occurs via

mother's breastmilk to cow's milk and multiple food antigens. There is

evidence of reduced Th1 response in these children. This is related to

associated IgA deficiency and low levels of cytokine transforming growth

factor beta.

CONCLUSIONS: The results of the present review demonstrate that the clinical

manifestations of cow's milk allergy are very diverse, with differences

between developing and developed countries. Understanding the immunologic

mechanisms is of key importance in understanding this diversity.

Publication Types:

Review

Review, Tutorial

PMID: 12839119 [PubMed - indexed for MEDLINE]

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Med Wieku Rozwoj. 2003;VII(2):279-287. Related Articles, Links

[study on immunological confirmation of allergy in children with

hypoimmunoglobulinemia]

[Article in Polish]

Siwinska-Golebiowska H, Czerwinska-Kartowicz I, Markiewicz K, Derentowicz P,

Golebiowska-Wawrzyniak M.

Zaklad Immunologii, Instytut Matki i Dziecka, ul. Kasprzaka 17a, 01-211

Warszawa, Poland. immunolog@...

The recognition of allergy in children with hypoimmunoglobulinemia is very

difficult because they have very low level or even lack of specific IgE

antibodies. Our research hypothesis was the possibility of detecting the

specific sensitization of lymphocytes T to food allergens in children with

hypoimmunoglobulinemia and with clinical symptoms of allergy.

Material: 32 children actually treated in our Immunology Outpatients

Department due to immunodeficiency connected with hypoimmunoglobulinemia and

with clinical suspicion of allergy. Methods: IgE concetration in serum and

IgE specific antibodies to food and pollens were examined by FEIA

CAP-SYSTEM. Lymphocyte specific response to allergens (cow's milk, gluten)

was examined by classical blast transformation test.

Immunological profile of children was also evaluated. Results: In the group

of 32 children we recognised: 20 children with predominantly antibody

deficiencies (2 - agammaglobulinemia; 8 - CVID; 5 - selective

immunoglobulines deficiency; 5 - hipoimmunoglobulinemia of infants) and 12

children who had combined immunodeficiency with hypoimmunoglobulinemia ( 3 -

AT; 8 - Nijmegen S; 1 - Di ). The children had atopic dermatitis and

clinical symptoms of allergy in respiratory and digestive tracts.

Concentration of IgE in serum of children was very low, even < 2KU/L,

Pediatric Phadiatop was negative, f2 and f79 were absent.

Using lymphocytes transformation test (culture stimulated with cow's milk

and gluten antigens) we detected sensitivity to cow's milk in 24 children

and additionally in 4 of them sensitivity to gluten. Conclusions: 1)

Laboratory difficulties in allergy diagnosis in children with

hypoimmunoglobulinemia by evaluation of specific IgE concentration in serum

may by caused by defect in biosynthesis of mentioned antibodies. 2) In

children with hypoimmunoglobulinemia the lymphocyte blastic transformation

test with specific allergens in cultures has a diagnostic value indicating

lymphocytes specific response to allergens.

PMID: 12878799 [PubMed - as supplied by publisher]

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