Effect of obesity on the complement response to OFTT
We subsequently divided the PCOS and control groups into ‘obese’ (BMI ≥ 30 kg/m2) and ‘non-obese’ (BMI <30 kg/m2) groups, and compared the effects of lipaemia on plasma levels of factor H, TCC and C3 in these groups (figure 3a-c respectively). Within the PCOS group, obesity had a profound effect on both baseline levels and AUC for factor H. Fasting factor H levels and AUC were both markedly increased in obese versus non-obese PCOS subjects (mean±SEM; baseline: 362.1±56.41 µg/ml versus 204.3±24.05 µg/ml respectively; p<0.001, and AUC: 1717±164.1 µg min/ml versus 1004±54.4 µg min/ml respectively; p<0.0001). Furthermore, across the whole cohort, strong correlations were observed between factor H AUC and each of HOMA-IR, visceral and subcutaneous fat area (Figure S1; p<0.0001 for all), and in fasting samples (cohort 1) between factor H and BMI, regardless of age (Figure S2; age 20-30: r2 0.43, p< 0.001 [PCOS] r2 0.62, p< 0.001 [controls]; age 30-40: r2 0.30, p< 0.001 [PCOS] r2 0.44, p< 0.001 [controls]; age 40-50: r2 0.77, p< 0.05 [PCOS], r2 0.36, p<0.001 [controls]). The TCC response to OFTT was also greater at 120 minutes in obese compared to non-obese PCOS subjects (figure 3b; mean±SEM: 0.54±0.12 µg/ml versus 0.29±0.04 µg/ml respectively; p<0.05). In contrast, no significant differences were observed in factor H and TCC OFTT responses between lean and obese controls. Baseline C3 levels and C3 AUC were significantly increased in obese compared to non-obese subjects irrespective of disease status, with C3 concentrations increasing gradually across the time course of the OFTT in both groups (Figure 3c).