Components of the Complement Cascade Differ in Polycystic Ovary Syndrome

Butler, Alexandra E.; Moin, Abu Saleh Md; Sathyapalan, Thozhukat; Atkin, Stephen L.

Abstract

Complement pathway proteins are reported to be increased in polycystic ovary syndrome (PCOS) and may be affected by obesity and insulin resistance. To investigate this, a proteomic analysis of the complement system was undertaken, including inhibitory proteins. In this cohort study, plasma was collected from 234 women (137 with PCOS 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), complement decay-accelerating factor (DAF) and complement factor H-related protein 5 (CFHR5). The alternative pathway of the complement system was primarily overexpressed 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 an increase in CFHR5, factor H and factor I (p < 0.01). Downstream complement factors iC3b and C3d, associated with an enhanced B cell response, and C5a, associated with an inflammatory cytokine release, were increased (p < 0.01). Hyperandrogenemia correlated positively with properdin and iC3b, whilst insulin resistance (HOMA-IR) correlated with iC3b and factor H (p < 0.05) in PCOS. BMI correlated positively with C3d, factor B, factor D, factor I, CFHR5 and C5a (p < 0.05). This comprehensive evaluation of the complement system in PCOS revealed the upregulation of components of the complement system, which appears to be offset by the concurrent upregulation of its inhibitors, with these changes accounted for in part by BMI, hyperandrogenemia and insulin resistance.

Citation

Butler, A. E., Moin, A. S. M., Sathyapalan, T., & Atkin, S. L. (2022). Components of the Complement Cascade Differ in Polycystic Ovary Syndrome. International Journal of Molecular Sciences, 23(20), Article 12232. https://doi.org/10.3390/ijms232012232

• Journal Article Type: Article
• Acceptance Date: Oct 10, 2022
• Online Publication Date: Oct 13, 2022
• Publication Date: Oct 2, 2022
• Deposit Date: Nov 6, 2022
• Publicly Available Date: Nov 7, 2022
• Journal: International Journal of Molecular Sciences
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 20
• Article Number: 12232
• DOI: https://doi.org/10.3390/ijms232012232
• Keywords: Polycystic ovary syndrome; Complement factors; C3; Properdin; Factor B
• Public URL: https://hull-repository.worktribe.com/output/4112163