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Panayiotis G. Vlachoyiannopoulos, Clio P. Mavragani, Efi Bourazopoulou, Anthi V. Balitsari, John G. Routsias
Anti-CD40 antibodies in antiphospholipid syndrome and systemic lupus erythematosus
Anti-2glycoprotein I (anti-2GPI) antibodies constitute the main autoantibody specificity in the sera of patients with antiphospholipid syndrome (APS). There is evidence that anti-2GPI antibodies induce the precoagulant activity of the endothelium by cross-linking the 2 glycoprotein I (2GPI) on the cell surface. Since 2GPI lacks intracellular domains, homology with other molecules such as CD40 that could initiate signaling, was extensively searched. A 86% homology between the amino acid position 239245 of the CD40 and 713 of the 2glycoprotein was found. The CD40 peptide corresponding to amino acids 239245 of the CD40 molecule was synthesized and coupled to a multiple antigenic peptide carrier. Antibodies to CD40 peptide were found in 61.5% APS patients (n=39), in 72.7% of systemic lupus erythematosus (SLE) positive for anti-2GPI antibodies (n=11) and 31.6% of SLE negative for anti-2GPI antibodies (n=19), but not in rheumatoid arthritis patients (n=28) or controls (n=36). Antibodies to CD40 peptide were associated with arterial thrombosis and/or brain microinfarcts. Affinity purified anti-CD40 peptide antibodies as well as affinity purified anti-2GPI antibodies recognized both, the 2GPI and the CD40 peptide. The specificity of this recognition was confirmed with homologous and heterologous inhibition experiments. Confocal microscopy experiments demonstrated this cross-recognition of CD40 and 2GPI molecules, by the purified anti-CD40 peptide antibodies, at the protein level. Thus, antibodies reacting with the 2GPI can react and potentially activate different cells which express CD40 molecules at their surface.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 92, 12/2004
Pages: 1303 - 1311