Classical and alternate complement factor overexpression in non-obese weight matched women with polycystic ovary syndrome does not correlate with vitamin D

• Published in: Frontiers in endocrinology (Lausanne) Vol. 13; p. 935750
• Main Authors: Moin, Abu Saleh Md, Sathyapalan, Thozhukat, Butler, Alexandra E., Atkin, Stephen L.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.12.2022
• Subjects: Complement C3b; complement factors; Complement System Proteins - genetics; Endocrinology; Female; Humans; Insulin Resistance; Obesity - complications; polycystic ovary syndrome; Polycystic Ovary Syndrome - complications; Properdin; Vitamin D; Vitamins; C3; C4; vitamin D; complement factors; polycystic ovary syndrome
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2022.935750

Women with polycystic ovary syndrome (PCOS) exhibit complement factor expression changes that may be obesity-driven rather than an intrinsic facet of PCOS; furthermore, complement changes have been associated with vitamin D deficiency, a common feature of PCOS. Therefore, complement pathway proteins and vitamin D levels may be linked in PCOS. We measured plasma levels of complement pathway proteins by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement for the classical (C4, C4a, and C4b) and alternative pathways (C3, C3b, iC3b, properdin, and factors B, D, and H) in weight and age-matched non-obese non-insulin resistant women with PCOS (n = 24) and control women (n = 24). Proteins that differed between groups were correlated with 25-hydroxyvitamin D (25(OH)D ) and 1,25-dihydroxyvitamin D (1,25(OH) D ), measured by isotope-dilution liquid chromatography tandem mass spectrometry. Women with PCOS had a higher free androgen index and anti-Mullerian hormone, though insulin resistance was comparable to controls; likewise, C-reactive protein, a marker of inflammation, was comparable between cohorts. In the alternative complement pathway, C3, iC3b, and properdin were increased in PCOS (p <0.05), while C4 in the classical pathway was increased (p <0.05). 25(OH)D levels positively correlated with C3b only in control subjects, with no correlation of 1,25(OH) D with any of the proteins. In a non-obese PCOS population matched for age, insulin resistance and inflammation, initiating proteins of the classical and alternate complement cascades were increased. However, a positive correlation with 25(OH)D was only seen for C3b in control subjects, with no correlation to 1,25(OH) D , suggesting that the increase in complement proteins in PCOS is vitamin D-independent.