Maternal immune responses to the fetus in early pregnancy and recurrent miscarriage

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

“…Similarly there were no differences between primary and secondary RM. The latter finding may be in contrast to earlier smaller studies suggesting that, with the limitation of small sample sizes, women with primary RM had less antileukocyte antibodies than women with secondary RM [15,16]. In a recent report using enzyme-linked immunoassay (ELISA)-based anti-HLA antibody detection, higher antibody frequencies were reported in the particular subgroup of secondary RM with a firstborn male infant, and a positive HLA antibody test result in early pregnancy in RM women was associated with a lower chance of a successful pregnancy outcome [14].…”

“…Regarding the suggested role of anti-HLA antibodies in RM, one may argue that idiopathic RM differs from RM of known etiology (where an alloimmune cause may be less probable) in terms of prevalence or distinct qualitative properties of alloantibody patterns, such as the ability to activate the classical complement pathway. In earlier studies, alloantibodies were reported to be less frequent in women who had lost all previous pregnancies (primary abortion) compared with those who experienced secondary abortion [15,16]. Recently, an increased prevalence of anti-HLA reactivity was noted among secondary aborters with a firstborn male infant, which was suggested to be related to an increased fetal cell microchimerism [14].…”

Recurrent pregnancy losses and the role of immunotherapy

“…Further studies by Rodger [87] showed that females incapable of antibody secretion could still carry pregnancy to term. In fact according to Sargent et al [90], the blocking antibody hypothesis has never been convincingly substantiated. These observations have put a cloud of doubt on the need for these antibodies in successful pregnancies.…”

Antitrophoblast antibodies are associated with recurrent miscarriages

“…Indeed, antibodies to paternal HLA are rarely identified before 28 weeks of gestation (6,12,(17)(18)(19)(20) and do not appear detrimental to pregnancy outcome (11,13). In contrast, antibodies that cross-react with HLA-negative syncytiotrophoblasts have been suggested to be highly correlated with RM (8,(21)(22)(23)(24).…”

“…Several studies indicate that these antibodies are frequently cytotoxic in nature and directed against paternal or paternally inherited alloantigens (5,6,(9)(10)(11)(12)(13). It appears that the differential activity of these antibodies in normal versus disturbed pregnancies is largely determined by the specific antigen against which they are directed (14)(15)(16)(17)(18).…”