RESEARCH - Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome

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Rheumatology (Oxford). 2006 Jul;45(7):833-41. Epub 2006 May 16.

Overlapping humoral autoimmunity links rheumatic fever and the

antiphospholipid syndrome.

Research Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer

52621, Israel.

OBJECTIVE: Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are

autoimmune diseases that share similar cardiac and neurological pathologies.

We assessed the presence of shared epitopes between M protein,

N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI),

the pathogenic molecules engaged in these autoimmune conditions. METHODS:

Sera from the APS patients were affinity-purified on beta2GPI and

beta2GPI-related peptide columns. Sera from RF patients were

affinity-purified on protein G column. The beta2GPI and M protein-related

peptides were prepared by conventional solid-phase peptide synthesis. The

enzyme-linked immunosorbent assay direct binding and inhibition studies were

performed on the RF and APS sera for the presence, and cross-reactivity, of

antibodies against beta2GPI, beta2GPI-related peptides, streptococcal M

protein, M-derived peptides and GlcNAc. RESULTS: Antibodies (Abs) to

beta2GPI were found in 24.4% of 90 RF patients. Antibodies against various

beta2GPI-related peptides were found in 1.1-36.7% of the patients. The

immunoglobulin G sera from RF patients possessed significant anti-beta2GPI

activity, while sera from APS patients contained a considerable

anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore,

affinity-purified anti-beta2GPI and anti-beta2GPI-related peptide Abs from

APS patients cross-reacted with streptococcal M protein and M5 peptide,

while beta2GPI and beta2GPI-related peptides inhibited anti-streptococcal M

protein activity from RF patients. The results were confirmed by immunoblot

analyses. The beta2GPI also inhibited anti-GlcNAc activity from APS patients

with chorea.

CONCLUSIONS: The results of our study, showing a considerable overlap of

humoral immunity in RF and APS, support a hypothesis that common pathogenic

mechanisms underlie the development of cardiac valve lesions and Central

Nervous System abnormalities in both diseases.

PMID: 16705050

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=Abstra\

ctPlus & list_uids=16705050

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