Antiphospholipid syndrome (APS) is a chronic and disabling condition characterized by recurrent thrombosis and miscarriages mediated by antibodies against phospholipid-binding proteins (aPL), such as beta<sub>2</sub>glycoprotein I (β<sub>2</sub>GPI).
Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intestinalis (R. int), and T and B cell autoepitopes in the APS autoantigen β<sub>2</sub>-glycoprotein I (β<sub>2</sub>GPI).
Recent advances allow us to propose antibodies targeting beta-2-glycoprotein I (β<sub>2</sub>-GPI) as the most specific antibodies associated with anti-phospholipid syndrome (APS).
The combination of the IgG anti-β<sub>2</sub> GPI domain I antibody and IgG/IgM anti-PS/PT antibody tests shows a high positive predictive value for the diagnosis of APS and a strong correlation with the aPL-S.
Moreover, the anti-β<sub>2</sub>GPI/β<sub>2</sub>GPI or APS-IgG/β<sub>2</sub>GPI complex-induced phosphorylation of mTOR in THP-1 cells was down-regulated through inhibition of p38 (10μM, SB203580) or ERK (5μM, U0126) rather than inhibition of JNK (90nM, SP600125) or NF-κB (20μM, PDTC).
The discovery in the 1990s that the protein beta-2-glycoprotein I (β<sub>2</sub>GPI) was an antigen of central importance in the antiphospholipid syndrome (APS) was soon followed by the development of ELISA assays capable of identifying anti-β<sub>2</sub>GPI antibodies recognizing this antigen.
These results suggest that the V-encoding allele and the homozygous VV genotype at position 247 of the beta2-GPI gene may play a role in the generation of anomalous beta2-GPI, with consequent auto-antibody production, and in phenotype expression of arterial and venous thrombosis in APS patients.
Taken together, these results indicate a direct cell synthesis of beta2-GPI, suggesting an antigenic function of beta2-GPI in the APS, including the CNS disease that occurs in this syndrome.