Evaluation of immunoglobulins subclasses and free-light chains in non-obese patients with polycystic ovary syndrome and correlations with hormonal and metabolic parameters: preliminary data.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and hyperinsulinemia that contribute to create a state of chronic low-grade inflammation. We performed an observational case-control study to investigate inflammatory and immunological parameters, such as IgG subclasses and free light chains (FLCs) and hemolytic complement activity (CH50) in non-obese PCOS, evaluating their relations with metabolic and hormonal parameters. PATIENTS AND METHODS: 36 subjects were studied: 16 PCOS patients (mean±SEM 27.13±1.82 age; BMI 24.1±0.9 kg/m2); 20 controls (aged 26.05±0.73; BMI 20.8 ± 0.4 kg/m2). The blood sample was collected for metabolic and hormonal parameters, IgG subclasses, k and λ FLCs, CH50. Hormones were measured by immunochemiluminometric assays; metabolic parameters by enzymatic assays; subclasses of IgG, FLCs, and CH50 were evaluated by the turbidimetric method. RESULTS: PCOS patients showed vs. controls lower IgG1, IgG2, IgG3 (mean±SEM 3.76±0.29 g/l, 2.63±0.20, 0.62±0.06, 0.34±0.08 vs. 6.49±0.35, 4.28±0.25, 0.84±0.07, 0.33±0.04, respectively) and higher levels of FLCs (k 12.22±0.71 vs. 6.03±0.30, λ 10.10±0.79 vs. 8.04±0.48 g/l) and CH50 (48.64±2.65 vs. 36.51±1.38 U/ml); we found correlation between IgG2 and free-testosterone (r=0.72, p=0.005) and CH50 and vitamin D (r=0.54, p=0.04); an inverse correlation was found between IgG1 and, respectively, ACTH (r=-0.57, p=0.02) and cortisol (r=0.78, p=0.001) in PCOS. CONCLUSIONS: In the complex scenario of low-grade inflammation in non-obese PCOS, we showed lower levels of main subclasses of IgG and higher CH50 levels, suggesting the involvement of other mechanisms other than the "classical" pathway of complement activation; FLCs could be attractive to monitor inflammation degree, disease activity and influence on hormonal status.

Serum immunoglobulin free light chain levels in systemic autoimmune rheumatic diseases.

Several reports have highlighted the abnormal increments of serum immunoglobulin free light chains (FLCs) in the course of systemic autoimmune rheumatic diseases (SARD), but a comparative analysis among different conditions is still lacking. A strong association between elevated FLC and hepatitis C virus (HCV)-related mixed cryoglobulinaemia (HCVMC) has been well established. Here, we aimed to analyse serum FLC levels in patients with four different SARD in comparison with HCVMC. Using a turbidimetric assay, free κ and λ chains were quantified in sera from 198 SARD patients (37 rheumatoid arthritis, RA; 47 systemic lupus erythematosus, SLE; 52 anti-phospholipid syndrome, APS; 62 primary Sjogren's syndrome, pSS), 62 HCVMC and 50 healthy blood donors (HD). All patient groups showed increased κ levels when compared to HD: 33·5 ± 2·6 mg/l in HCVMC, 26·7 ± 2·3 mg/l in RA, 29·7 ± 1·9 mg/l in SLE, 23·8 ± 1·1 mg/l in APS, 24·2 ± 1·1 mg/l in pSS; 10·1 ± 0·6 mg/l in HD. Free λ levels displayed a significant increase only for HCVMC (20·4 ± 1·4 mg/l) and SLE (18·4 ± 1·0 mg/l) compared to HD (13·6 ± 0·9 mg/l). The increase of κ compared to λ takes into account a κ /λ ratio of 1·6 for all groups. Our results substantially analyse and strengthen the association between FLC and SARD focusing the questions regarding their role in the pathogenesis and diagnosis of human diseases. Unfortunately, the biochemical differences distinguishing normal from pathological FLC have not been identified. Production of different isotypes is probably connected to still-unknown pathways.

Lack of association between Vitamin D status and free light chains profile with different chronic HCV-related liver and extrahepatic disorders.

OBJECTIVE: A still uncertain association between vitamin D levels and HCV chronic liver diseases has been reported. Increased levels of serum-free light chains (FLCs) and an altered k/λ FLC ratio correlate with Mixed Cryoglobulinemia (MC) vasculitis and/or B-cell non-Hodgkin's lymphoma in HCV-positive patients. We aimed to investigate the possible role of vitamin D, vitamin D Binding Protein (DBP), and FLCs levels as a tool for discriminating different stages of HCV- related MC and chronic liver diseases. PATIENTS AND METHODS: Sixty-five untreated patients were retrospectively enrolled and 21 healthy blood donors (HBD) were used as controls. Vitamin D, DBP, FLCs, and cryoglobulins levels were measured. Based on cryoglobulins, patients were divided in three subgroups (without cryoglobulins, type II, and type III). RESULTS: We didn't find any significant differences in vitamin D and DBP levels between HCV patients' main groups and HBD. Serum FLCs levels were significantly higher in HCV patients than in HBD. FLCs ratio among patients' subgroups did not reveal differences. CONCLUSIONS: Our results confirm the presence of an increased serum level of FLCs in HCV patients and suggest that nor vitamin D and DBP or FLC levels can be considered reliable biomarkers for discriminating different stages of HCV-associated chronic liver diseases and/or HCV-associated extrahepatic manifestation. We confirm that serological FLCs levels are significantly higher in patients than in HBD as a signature of B cell activation in course of HCV infection.