Table 1 Evidence for proposed mechanisms of genetic and environmental involvement in APS development
From: Pathophysiology of the antiphospholipid antibody syndrome
Experimental model | Implications/findings | |
|---|---|---|
Genetic | Animal studies | • Evidence for antigen driven stimulation for pathogenic aPL production |
• Complementary gene action of 2 independently segregating major dominant alleles produce disease characteristic | ||
• Role for modifying alleles (e.g. Yaa) | ||
• Role for hormones in modifying genetic susceptibility | ||
Human family HLA Studies | • Most consistent associations: HLA-DR4 and DRw53 | |
• Others: DR7, DQw3, DQw7, A30, Cw3, B60 | ||
Human population HLA studies | • Most consistent associations: HLA-DR4, DR7, DRw53, DQB1*0302 | |
• Others: DRB1*04, DQB1*0301/4, DQB1*0604/5/6/7/8/9, DQA1*0102, DQA1*0301/2 | ||
• DRB1*09 in Japanese patients | ||
• C4A/C4B null alleles in African American patients | ||
Human non-HLA studies | • Several non-HLA genes associated with increased thrombosis [G20210 A, AT-III, F5G1691 A, β2GPI val247leu polymorphism, F13A1, GP1a/IIa polymorphisms] | |
Environmental | Infectious agents | • Molecular mimicry [e.g. CMV, AdV,H. influenzae, N. gonorrhoae, C. tetani] |
• Selective destruction/activation of unique lymphocyte subsets | ||
• Cytokine release | ||
• Cryptic antigen exposure (necrosis/apoptosis) | ||
Drugs/vaccination | • Neoantigen formation | |
• Altered antigen processing and presentation | ||
Malignancies | • Neoantigen formation (tumor, immunomodulatory therapy) | |