Background Autoantibodies, low complement levels and higher NK cell counts are present in a subset of women with recurrent pregnancy loss (RPL). The combination of these abnormalities might be a surrogate profile for the presence of a subclinical inflammatory or autoimmune condition.
Objectives In a cohort of women with unexplained RPL we evaluated if an immunological profile combining innate and adaptive immunity mediators was associated with the presence of distinct clinical characteristics that are commonly observed in autoimmune diseases and if it was a risk factor for developing these diseases. In a small subset of women with the immunological profile we evaluated the activation status of CD4+ and CD8+ cells.
Methods We evaluated 366 women with RPL defined as 2 or more pregnancy losses and 93 control women. We defined the immune profile as the presence of 2 or more of the following abnormalities: Peripheral blood NK cell percentages >15%, positive antiphospholipid antibodies, positive antinuclear antibodies, positive anti-thyroid antibodies, low complement C3 levels and low C4 complement levels. Evolution to autoimmune diseases was detected during follow-up. Lymphocyte subsets were evaluated by flow-cytometry. Statistics: Chi-square test. Logistic regression.
Results The prevalence of women with 2 or more immunological abnormalities was 57 out of 366 women (15.6%) and was significantly higher than in control women. Demographic clinical characteristics were similar in women with 2 or more immunological abnormalities as compared with women with only one immunological alteration or no abnormalities. The presence of the immunological profile was significantly associated with the presence of the following clinical characteristics: Leucopenia (p=0.048), lymphopenia (p=0.007), livedo reticularis (p=0.01), cutaneous rash (p=0.009), and arthritis (p=0.001). During follow-up 17 patients (4.6%) developed an inflammatory or autoimmune disease that was not present at the time of the diagnose of RPL including SLE and lupus like disease. Women with the immunological profile were at higher risk for evolution into these diseases: OR 4.19, 95% confidence interval 1.52–11.51, p=0.0055. In 10 women with the immunological profile we observed significantly higher levels of CD4+DR+ and CD8+DR+ T-cells as compared with women without the immune profile.
Conclusions A subgroup of women with unexplained RPL are at risk of developing clinical characteristics of an inflammatory or autoimmune disease. In this regard, the immunological evaluation of women with RPL might be necessary not only to identify a potential cause of abortion but also to identify women that could require a more careful clinical follow-up. Higher CD4+DR+ and CD8+DR+ T-cells might be a pathogenic pathway leading to development of autoimmune diseases in RPL women.
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Acknowledgements Research Funds. Fundacion Salud 2000. Madrid Spain.
Disclosure of Interest None declared