Endocrine Abstracts

Background: Age-associated double negative (DN) B memory cells lacking surface expression of CD27 and IgD have been associated with proinflammatory characteristics, higher disease activity in autoimmune diseases and disease-specific autoantibodies. We studied the distribution of DN B cells in Polycystic Ovary Syndrome (PCOS), their surface markers and cytokine production.

Methods: CD19+ cell subpopulations on the basis of IgD and CD27 expression were phenotypically analyzed from normal-weight PCOS patients with clinical hyperandrogenemia [n=18, age 27.5±11.2 years, body mass index (BMI) 27.3±14] and normal-weight controls (HD, n=17; age 37±16.3 years, BMI 25.1±10.9) in order to evaluate significantly enhanced frequencies of DN B cells. The exclusion criteria were use of insulin-sensitizers, contraceptives, steroids, diabetes type 1 and chronic inflammatory bowel disease, recorded at clinical visits for hormonal and metabolic data. Flow cytometry for surface markers and intracellular cytokine staining was performed.

Results: Phenotypic analysis showed a significant remodeling of B cell repertoire in PCOS. The frequency of DN B memory cells was significantly higher in PCOS patients than in the HD (P=0.002) along with declined IgD+B cell compartment (P=0.011). Notably, absolute numbers of DN cells within PCOS cohort with 45.3 (±39.9) cells/μl were significantly different to HD 23.1 (±11.9) cells/μl (P=0.046). DN B cells surface expression of IgG, CD38 and CD86, along with the analysis of cytokine production is ongoing. A positive correlation between the percentage of DN B cells and BMI has been found in PCOS patients (P=0.01) but not in HD.

Conclusion: Our pilot cohort of PCOS patients showed increased peripheral expansion of DN B cells. The dominating isotypes remain to be clarified. We speculate these cells could contribute to inflammation by T cell induction and the production of proinflammatory cytokines. Though increased adipose tissue mass is a determining factor in inflammation, PCOS might trigger additional specific antigenic stimuli.