title: 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-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.
authors.affiliation: Research Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: I
authors.initials: I
authors.lastname: Krause
authors.forename: L
authors.initials: L
authors.lastname: Magrini
authors.forename: G
authors.initials: G
authors.lastname: Spina
authors.forename: J
authors.initials: J
authors.lastname: Kalil
authors.forename: S
authors.initials: S
authors.lastname: Jacobsen
authors.forename: H J
authors.initials: HJ
authors.lastname: Thiesen
authors.forename: M W
authors.initials: MW
authors.lastname: Cunningham
authors.forename: L
authors.initials: L
authors.lastname: Guilherme
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000117:Acetylglucosamine / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001667:Binding, Competitive; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology; D003429:Cross Reactions; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012213:Rheumatic Fever / Q000276:immunology*; D053482:beta 2-Glycoprotein I
chemical_list: D000942:Antigens, Bacterial; D001323:Autoantibodies; D001324:Autoantigens; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I; C014689:streptococcal M protein; D000117:Acetylglucosamine