Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome

M. Blank, I. Krause, L. Magrini, G. Spina, J. Kalil, S. Jacobsen, H. J. Thiesen, M. W. Cunningham, L. Guilherme, Y. Shoenfeld*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)833-841
Number of pages9
Issue number7
StatePublished - Jul 2006


  • Anti-M-protein Abs
  • Anti-β2GPI Abs
  • Carditis
  • Chorea
  • Streptococcal infection


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