Rheumatology Advance Access published online on May 16, 2006
Rheumatology, doi:10.1093/rheumatology/kel118
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1 Research Center for Autoimmune Diseases, Sheba Medical Center, Tel-Aviv University, Israel
* To whom correspondence should be addressed. 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- Methods: Sera from the APS patients were affinity-purified on Results: Antibodies (Abs) to 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.
Received January 24, 2006
Accepted March 1, 2006
Original Papers
Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome
M. Blank 1,
I. Krause 2,
L. Magrini 1,
G. Spina 3,
J. Kalil 3,
S. Jacobsen 4,
H. J. Thiesen 5,
M. W. Cunningham 6,
L. Guilherme 3,
and
Y. Shoenfeld 7 *
2 Research Center for Autoimmune Diseases, Sheba Medical Center, Tel-Aviv University, Israel; Department of Medicine ‘E’, Rabin Medical Center, Beilinson Campus; Sackler Faculty of Medicine, Tel-Aviv University, Israel
3 Heart Institute (InCor), School of Medicine, University of Sao Paulo, Brazil; Institute for Immunology Investigation, Millennium Institute, Sao Paulo, Brazil
4 Hvidovre Hospital, Hvidovre, Denmark
5 Institute of Immunology, University of Rostock, Schillingallee 70, 18055 Rostock, Germany
6 Department of Microbiology and Immunology, Biomedical Research Center, University of Oklahoma Health Sciences Center, OK 73104, USA
7 Research Center for Autoimmune Diseases, Sheba Medical Center, Tel-Aviv University, Israel; Incumbent of the Laura Schwarz-Kipp Chair for Autoimmunity, Tel Aviv University, Israel
Y. Shoenfeld, E-mail: Shoenfel{at}post.tau.ac.il
Abstract 
-d-glucosamine (GlcNAc) and 2 glycoprotein-I (2GPI), the pathogenic molecules engaged in these autoimmune conditions.2GPI and 2GPI-related peptide columns. Sera from RF patients were affinity-purified on protein G column. The 2GPI 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 2GPI, 2GPI-related peptides, streptococcal M protein, M-derived peptides and GlcNAc.2GPI were found in 24.4% of 90 RF patients. Antibodies against various 2GPI-related peptides were found in 1.1-36.7% of the patients. The immunoglobulin G sera from RF patients possessed significant anti-2GPI activity, while sera from APS patients contained a considerable anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore, affinity-purified anti-2GPI and anti-2GPI-related peptide Abs from APS patients cross-reacted with streptococcal M protein and M5 peptide, while 2GPI and 2GPI-related peptides inhibited anti-streptococcal M protein activity from RF patients. The results were confirmed by immunoblot analyses. The 2GPI also inhibited anti-GlcNAc activity from APS patients with chorea.2GPI Abs; Anti-M-protein Abs; Carditis; Chorea..
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