Prevalence and qualitative properties of circulating anti-human leukocyte antigen alloantibodies after pregnancy: No association with unexplained recurrent miscarriage

In pregnant women, circulating alloantibodies, triggered by exposure to paternal HLA antigens, are frequently detectable. The finding of lower alloantibody levels in women who experience spontaneous abortion (miscarriage) has led to the speculation that antipaternal antibodies could favor maintenance of pregnancy, whereas their lack poses a risk of miscarriage. Postulating a role of alloantibodies in the pathogenesis of unexplained abortion, we examined whether different categories of recurrent miscarriage (RM) can be distinguished according to prevalence or distinct qualitative properties of anti-human leukocyte antigen (HLA) antibody patterns. Sera obtained from 167 women with RM were assessed for complement- and non-complement-fixing anti-HLA alloreactivity using Luminex-based bead array technology. Women with RM had less often detectable anti-HLA class I and/or II reactivity (19%) compared with a control group of 96 multiparous women without a history of miscarriage (49%). However, analysis of different categories of RM (unknown [n = 112] versus known cause [n = 55]; primary [n = 125] versus secondary RM [n = 42]) did not reveal any differences regarding antibody prevalence, number of targeted HLA single antigens, antigen specificity, binding density, or complement-fixing ability of detected alloantibodies. Our results do not support a link between anti-HLA antibody formation and RM, and argue against a diagnostic value of alloantibody detection in the diagnostic work-up of women with RM.