HHV6 in MS & CFS

[Guest guest]

Ablashi et al provide further documentation of HHV6 in MS and CFS (1);

and their study is complementary to the recent findings of Knox,

Carrigan, et al (2). Together, when these studies are joined with V

Singh's HHV6 and MV findings (3), one wonders when neurologists and

psychologists will begin to request titer determinations and peripheral

viral-load quantifications in ASD kids -- especially since anti-HHV6

pharmaceuticals are available.

In regard to VK's study, I wonder if the " not quite significant "

difference between titers of controls and autistic kids arose because a

younger population would have more kids whose HHV6 infection was

somewhat recent. Regardless, although titers can provide a clue,

quantitation of viral load and of viral-activation status (2) seems a

more important determination.

J Clin Virol 2000 May;16(3):179-91

Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic

fatigue

syndrome (CFS) patients.

Ablashi DV et al.

BACKGROUND: HHV-6 is a ubiquitous virus and its infection usually occurs

in

childhood and then becomes a latent infection. HHV-6 reactivation has

been shown

to play a role in the pathogenesis of AIDS and several other diseases.

OBJECTIVES: To determine what role HHV-6 infection or reactivation plays

in the

pathogenesis of multiple sclerosis (MS) and chronic fatigue syndrome

(CFS).

RESULTS: Twenty-one MS and 35 CFS patients were studied and followed

clinically.

In these patients, we measured HHV-6 IgG and IgM antibody levels and

also

analyzed their peripheral blood mononuclear cells (PBMCs) for the

presence of

HHV-6, using a short term culture assay. In both MS and CFS patients, we

found

higher levels of HHV-6 IgM antibody and elevated levels of IgG antibody

when

compared to healthy controls. Seventy percent of the MS patients studied

contained IgM antibodies for HHV-6 late antigens (capsid), while only

15% of the

healthy donors (HD) and 20% of the patients with other neurological

disorders

(OND) had HHV-6 IgM antibodies. Higher frequency of IgM antibody was

also

detected in CFS patients (57.1%) compared to HD (16%). Moreover, 54% of

CFS

patients exhibited antibody to HHV-6 early protein (p41/38) compared to

only

8.0% of the HD. Elevated IgG antibody titers were detected in both the

MS and

the CFS patients. PBMCs from MS, CFS and HD were analyzed in a short

term

culture assay in order to detect HHV-6 antigen expressing cells and to

characterize the viral isolates obtained as either Variant A or B.

Fifty-four

percent of MS patients contained HHV-6 early and late antigen producing

cells

and 87% of HHV-6 isolates were Variant B. Isolates from CFS, patients

were

predominately Variant A (70%) and isolates from HD were predominately

Variant B

(67%). Moreover, one isolate from OND was also Variant B. Persistent

HHV-6

infection was found in two CFS patients over a period of 2.5 years and

HHV-6

specific cellular immune responses were detected in PBMCs from ten CFS

patients.

CONCLUSION: In both MS and CFS patients, we found increased levels of

HHV-6

antibody and HHV-6 DNA. A decrease in cellular immune responses was also

detected in CFS patients. These data suggest that HHV-6 reactivation

plays a

role in the pathogenesis of these disorders.

2: Clin Infect Dis 2000 Oct;31(4):894-903

Human herpesvirus 6 and multiple sclerosis: systemic active infections

in

patients with early disease.

Knox KK, Brewer JH, Henry JM, Harrington DJ, Carrigan DR

By means of immunohistochemical staining, cells actively infected with

human herpesvirus 6 (HHV-6) were found in central nervous system tissues

from 8 (73%) of 11 patients with definite multiple sclerosis (MS).

Interestingly, 17 (90%) of 19 tissue sections showing active

demyelination were positive for HHV-6-infected cells compared with only

3 (13%) of 23 tissue sections free of active disease

(P<.0001).

Central nervous system tissues from 2 of 28 normal persons and

patients with other inflammatory demyelinative diseases were positive

for HHV-6-infected cells (P<.0001), and the 2 positive cases were

diagnosed as having HHV-6 leukoencephalitis.

By use of a rapid culture assay, blood samplesfrom 22 (54%) of 41

patients with definite MS were found to contain active HHV-6 infections,

compared with 0 of 61 normal controls (P<.0001).

No significant difference was found between HHV-6 viremia-positive

and HHV-6 viremia-negative MS patients with respect to type of disease

(relapsing/remitting or

progressive). In contrast, patients with active HHV-6 viremia were

significantly

younger and had shorter durations of disease than did HHV-6

viremia-negative

patients.

3. Clin Immunol Immunopathol 1998 Oct;89(1):105-8

Serological association of measles virus and human herpesvirus-6 with

brain

autoantibodies in autism.

Singh VK, Lin SX, Yang VC

College of Pharmacy, University of Michigan, Ann Arbor, Michigan,

48109-1065,

USA.

Considering an autoimmunity and autism connection, brain autoantibodies

to myelin basic protein (anti-MBP) and neuron-axon filament protein

(anti-NAFP) have been found in autistic children. In this current study,

we examined associations between virus serology and autoantibody by

simultaneous analysis of measles virus antibody (measles-IgG), human

herpesvirus-6 antibody (HHV-6-IgG), anti-MBP, and anti-NAFP.

We found that measles-IgG and HHV-6-IgG titers were moderately

higher in autistic children but they did not significantly differ from

normal controls. Moreover, we found that a vast majority of virus

serology-positive autistic sera was also positive for brain

autoantibody:

(i) 90% of measles-IgG-positive autistic sera was also positive for

anti-MBP;

(ii) 73% of measles-IgG-positive autistic sera was also positive for

anti-NAFP;

(iii) 84% of HHV-6-IgG-positive autistic sera was also positive for

anti-MBP; and

(iv) 72% of HHV-6-IgG-positive autistic sera was also positive for

anti-NAFP.

This study is the first to report an association between virus

serology and brain

autoantibody in autism; it supports the hypothesis that a virus-induced

autoimmune response may play a causal role in autism.

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