Anti-annexin V IgM and IgG autoantibodies and the risk of idiopathic recurrent spontaneous miscarriage

Anti-annexin V antibodies have been identified as risk factors for recurrent spontaneous miscarriage (RSM) in some, but not all previous studies. We investigated the association between anti-annexin IgM and IgG in RSM cases and control women. Blood samples from 244 women with idiopathic RSM, and 283 multi-parous control women were tested for anti-annexin V antibodies by ELISA. A significant elevation in anti-annexin V IgM and IgG was seen in the RSM cases. An increased prevalence of elevated anti-annexin V IgM and to a lesser extent anti-annexin V IgG was seen in RSM patients. Receiver operating characteristic analysis indicated that the area under the curve for anti-annexin V IgM was 0.916, and for anti-annexin V IgG was 0.725. A systematic shift in anti-annexin V IgM and IgG distributions toward higher values occurred in RSM women, which was confirmed by percentile analysis. For each of the anti-annexin V isotypes, the adjusted odds ratio increased as the percentile value increased; the strongest risk was for anti-annexin V IgM, in which the 99th percentile (P99) was associated with a 165-fold higher risk than P50, and for anti-annexin V IgG where P99 was associated with a 38-fold higher risk than P50. In addition, a higher prevalence of elevated anti-annexin V IgM and anti-annexin V IgG was seen in RSM cases than in control women. We conclude that anti-annexin V IgM and IgG antibody positivity are independent risk factors for RSM.