Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome

Abstract

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-β-D-glucosamine (GlcNAc) and β2 glycoprotein-I (β2GPI), the pathogenic molecules engaged in these autoimmune conditions. Methods: Sera from the APS patients were affinity-purified on β2GPI and β2GPI-related peptide columns. Sera from RF patients were affinity-purified on protein G column. The β2GPI 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 β2GPI, β2GPI-related peptides, streptococcal M protein, M-derived peptides and GlcNAc. Results: Antibodies (Abs) to β2GPI were found in 24.4% of 90 RF patients. Antibodies against various β2GPI-related peptides were found in 1.1-36.7% of the patients. The immunoglobulin G sera from RF patients possessed significant anti-β2GPI activity, while sera from APS patients contained a considerable anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore, affinity-purified anti-β2GPI and anti-β2GPI-related peptide Abs from APS patients cross-reacted with streptococcal M protein and M5 peptide, while β2GPI and β2GPI-related peptides inhibited anti-streptococcal M protein activity from RF patients. The results were confirmed by immunoblot analyses. The β2GPI 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. © 2006 Oxford University Press.