Anti-CD40 antibodies in antiphospholipid syndrome and systemic lupus erythematosus

Summary

Anti-β2glycoprotein I (anti-β2GPI) antibodies constitute the main autoantibody specificity in the sera of patients with antiphospholipid syndrome (APS). There is evidence that antiβ2GPI antibodies induce the precoagulant activity of the endothelium by cross-linking the β2 glycoprotein I (β2GPI) on the cell surface. Since β2GPI 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 239-245 of the CD40 and 7-13 of the β2glycoprotein was found. The CD40 peptide corresponding to amino acids 239-245 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 β2GPI antibodies (n=11) and 31.6% of SLE negative for antiβ2GPI 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-β2GPI antibodies recognized both, the β2GPI 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 β2GPI molecules, by the purified anti-CD40 peptide antibodies, at the protein level. Thus, antibodies reacting with the β2GPI can react and potentially activate different cells which express CD40 molecules at their surface.

Keywords

CD40 peptides - antibodies - antiphospholipid syndrome - β2 glycoprotein I - systemic lupus erythematosus

^* These authors contributed equally to the project.

• References

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