Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients
Introduction: Upregulation of complement system factors are reported to be increased in polycystic ovary syndrome (PCOS) and may be due to obesity and insulin resistance rather than inherently due to PCOS. We directly compared complement factors from an obese, insulin-resistant PCOS population to a...
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MDPI AG
2023-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/15/2002 |
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| author | Alexandra E. Butler Abu Saleh Md Moin Thozhukat Sathyapalan Stephen L. Atkin |
| author_facet | Alexandra E. Butler Abu Saleh Md Moin Thozhukat Sathyapalan Stephen L. Atkin |
| author_sort | Alexandra E. Butler |
| collection | DOAJ |
| description | Introduction: Upregulation of complement system factors are reported to be increased in polycystic ovary syndrome (PCOS) and may be due to obesity and insulin resistance rather than inherently due to PCOS. We directly compared complement factors from an obese, insulin-resistant PCOS population to a nonobese, non-insulin-resistant PCOS population in a proteomic analysis to investigate this. Methods: Plasma was collected from 234 women (137 with PCOS and 97 controls) from a biobank cohort and compared to a nonobese, non-insulin-resistant population (24 with PCOS and 24 controls). Slow off-rate modified aptamer (SOMA) scan plasma protein measurement 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). Results: The alternative pathway of the complement system was overexpressed in both obese and nonobese PCOS, with increased C3 (<i>p</i> < 0.05) and properdin (<i>p</i> < 0.01); additionally, factor B increased in obese PCOS (<i>p</i> < 0.01). For inhibitors of this pathway, factor I was increased (<i>p</i> < 0.01) in both slim and obese PCOS, with an increase in CFHR5 and factor H in obese PCOS (<i>p</i> < 0.01). Complement factors iC3b, C3d and C5a, associated with an enhanced B cell response and inflammatory cytokine release, were increased in both slim and obese PCOS (<i>p</i> < 0.05). C3a and its product, C3adesArg, were both significantly elevated in nonobese PCOS (<0.01) but not altered in obese PCOS. Hyperandrogenemia correlated positively with properdin and iC3b in obese PCOS (<i>p</i> < 0.05) but not in nonobese PCOS. There was no association with insulin resistance. BMI correlated positively in both groups with factor B, factor H and C5a. Additionally, in obese PCOS, BMI correlated with C3d, factor D, factor I, CFHR5 and C5a (<i>p</i> < 0.05), and in nonobese PCOS, BMI correlated with properdin, iC3b, C3, C3adesArg, C3a, C4, C5, C5a and C1q. In obese controls, BMI correlated with C3, C3desArg, C3a, C3d, C4, factor I, factor B, C5a and C5, whilst in nonobese controls, BMI only correlated negatively with C1q. Comparison of nonobese and obese PCOS showed that properdin, C3b, iC3b, C4A, factor D, factor H and MBL differed. Conclusion: The upregulation of the alternative complement pathway was seen in nonobese PCOS and was further exacerbated in obese PCOS, indicating that this is an inherent feature of the pathophysiology of PCOS that is worsened by obesity and is reflected in the differences between the nonobese and obese PCOS phenotypes. However, the increase in the complement proteins associated with activation was counterbalanced by upregulation of complement inhibitors; this was evident in both PCOS groups, suggesting that insults, such as a cardiovascular event or infection, that cause activation of complement pathways may be amplified in PCOS. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:29:36Z |
| publishDate | 2023-08-01 |
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| spelling | doaj.art-9e40bbf622a64a608692c2674e8cf0f52023-11-18T22:45:31ZengMDPI AGCells2073-44092023-08-011215200210.3390/cells12152002Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome PatientsAlexandra E. Butler0Abu Saleh Md Moin1Thozhukat Sathyapalan2Stephen L. Atkin3Royal College of Surgeons in Ireland Bahrain, Busaiteen P.O. Box 15503, Adliya, BahrainRoyal College of Surgeons in Ireland Bahrain, Busaiteen P.O. Box 15503, Adliya, BahrainAcademic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RU, UKRoyal College of Surgeons in Ireland Bahrain, Busaiteen P.O. Box 15503, Adliya, BahrainIntroduction: Upregulation of complement system factors are reported to be increased in polycystic ovary syndrome (PCOS) and may be due to obesity and insulin resistance rather than inherently due to PCOS. We directly compared complement factors from an obese, insulin-resistant PCOS population to a nonobese, non-insulin-resistant PCOS population in a proteomic analysis to investigate this. Methods: Plasma was collected from 234 women (137 with PCOS and 97 controls) from a biobank cohort and compared to a nonobese, non-insulin-resistant population (24 with PCOS and 24 controls). Slow off-rate modified aptamer (SOMA) scan plasma protein measurement 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). Results: The alternative pathway of the complement system was overexpressed in both obese and nonobese PCOS, with increased C3 (<i>p</i> < 0.05) and properdin (<i>p</i> < 0.01); additionally, factor B increased in obese PCOS (<i>p</i> < 0.01). For inhibitors of this pathway, factor I was increased (<i>p</i> < 0.01) in both slim and obese PCOS, with an increase in CFHR5 and factor H in obese PCOS (<i>p</i> < 0.01). Complement factors iC3b, C3d and C5a, associated with an enhanced B cell response and inflammatory cytokine release, were increased in both slim and obese PCOS (<i>p</i> < 0.05). C3a and its product, C3adesArg, were both significantly elevated in nonobese PCOS (<0.01) but not altered in obese PCOS. Hyperandrogenemia correlated positively with properdin and iC3b in obese PCOS (<i>p</i> < 0.05) but not in nonobese PCOS. There was no association with insulin resistance. BMI correlated positively in both groups with factor B, factor H and C5a. Additionally, in obese PCOS, BMI correlated with C3d, factor D, factor I, CFHR5 and C5a (<i>p</i> < 0.05), and in nonobese PCOS, BMI correlated with properdin, iC3b, C3, C3adesArg, C3a, C4, C5, C5a and C1q. In obese controls, BMI correlated with C3, C3desArg, C3a, C3d, C4, factor I, factor B, C5a and C5, whilst in nonobese controls, BMI only correlated negatively with C1q. Comparison of nonobese and obese PCOS showed that properdin, C3b, iC3b, C4A, factor D, factor H and MBL differed. Conclusion: The upregulation of the alternative complement pathway was seen in nonobese PCOS and was further exacerbated in obese PCOS, indicating that this is an inherent feature of the pathophysiology of PCOS that is worsened by obesity and is reflected in the differences between the nonobese and obese PCOS phenotypes. However, the increase in the complement proteins associated with activation was counterbalanced by upregulation of complement inhibitors; this was evident in both PCOS groups, suggesting that insults, such as a cardiovascular event or infection, that cause activation of complement pathways may be amplified in PCOS.https://www.mdpi.com/2073-4409/12/15/2002polycystic ovary syndromecomplement factorsfactor HC3properdinfactor B |
| spellingShingle | Alexandra E. Butler Abu Saleh Md Moin Thozhukat Sathyapalan Stephen L. Atkin Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients Cells polycystic ovary syndrome complement factors factor H C3 properdin factor B |
| title | Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients |
| title_full | Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients |
| title_fullStr | Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients |
| title_full_unstemmed | Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients |
| title_short | Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients |
| title_sort | complement dysregulation in obese versus nonobese polycystic ovary syndrome patients |
| topic | polycystic ovary syndrome complement factors factor H C3 properdin factor B |
| url | https://www.mdpi.com/2073-4409/12/15/2002 |
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