Abstract
Introduction
It has been shown that complement factors are increased in polycystic ovary syndrome (PCOS) and that these may be affected by obesity and insulin resistance. Hypothetically, this may increase cardiometabolic risk but, paradoxically, increased clotting is not a feature of PCOS. To investigate this, proteomic analysis of the complement system was undertaken, including inhibitory proteins.
Methods
Plasma was collected from 244 women (147 with PCOS and all 3 diagnostic features and 97 controls). Somalogic proteomic analysis was undertaken for the following complement system proteins: C1q, C1r, C2, C3, C3a, iC3b, C3b, C3d, C3adesArg, C4, C4a, C4b, C5, C5a, C5b-6 complex, C8, properdin, Factor B, Factor D, Factor H, Factor I, Mannose-binding protein C (MBL), Mannan-binding lectin serine protease 1 (MASP3), Complement decay-accelerating factor (DAF) and Complement factor H-related protein 5 (CFHR5).
Results
The alternative pathway of the complement system was primarily activated in PCOS, with increased C3 (p<0. 05), properdin and Factor B (p<0. 01). In addition, inhibition of this pathway was also seen in PCOS, with increase in CFHR5, Factor H and Factor I (p<0. 01). There were also increases in the downstream complement factors of iC3b and C3d, associated with an enhanced B cell response, and C5a, associated with inflammatory cytokine release (p<0. 01).
Conclusion
This is the most comprehensive evaluation of the complement system in PCOS to date and reveals upregulation of the alternative complement system that appears to be offset by the concurrent upregulation of its inhibitors. However, any additional dysregulation of the system, such as occurs with COVID19 infection, may give rise to an increased risk for clotting in women with PCOS.
Presentation: No date and time listed