Humoral immune response to an allogenic foetus in normal fertile women and recurrent aborters

Abstract

BackgroundSeveral humoral immune factors are responsible for a successful pregnancy. There are a few studies, which demonstrate the role of antipaternal cytotoxic antibodies (APCA) and mixed lymphocyte reaction blocking factor (MLR-Bf) in the maintenance of pregnancy. However, these factors have not been studied in women with history of recurrent spontaneous abortion (RSA). We designed this study to review the role of APCA and MLR-Bf in normal pregnancy as well as in women with a history of RSA.MethodsOne hundred and five women with unexplained recurrent spontaneous abortion were included in the present study. These women were screened for all other known causes of recurrent abortion. We also included 60 normal fertile women, fifteen from each trimester and fifteen women during the post partum period (up to six months). RSA and controls (normal pregnancy) were matched for age, caste, and socio economic background and also for parity. APCA and MLR-Bf were evaluated in all the groups. All women with RSA who conceived during the study period were on follow up.ResultsWe have analyzed the status of APCA and MLR-Bf in normal pregnancy (different gestational periods and during post partum), and in women with history of RSA. Our results show that APCA was significantly higher in controls as compared to RSA women. MLR-Bf was directed against the husbands' cells in normal pregnancy and was virtually absent in RSA women.ConclusionOur results indicate that there is a significantly low titer of APCA and MLR-Bf in women with recurrent spontaneous abortion. This highlights the role of these factors in the maintenance of successful pregnancy.

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

“…This apparent difference is in concordance with previous studies where circulating alloreactivity was reported in 20 -50% of women with successful pregnancies compared with less than 10% in women with abortions [4,5,13,14,21,22]. One explanation for the higher proportion of sensitized subjects among multipara could be the longer exposure time to the fetus in normal pregnancy, which may give more opportunities to induce a humoral immune response.…”

“…In most of the earlier studies, cell-based techniques for alloantibody detection, such as leukoagglutination [2,21], CDC [1,5,12,13,22], or flow-cytometric cross-matching [26,27] were used to detect alloantibodies. A weakness of cell-based assays is their failure to distinguish between HLA-specific alloantibodies and antibodies directed to non-HLA antigens expressed on the surface of test lymphocytes.…”

“…Indeed, earlier studies did not provide evidence for an association between alloantibody formation and miscarriage or obstetric complications [3,4]. Of note, previous studies have shown that APA detected by leukoagglutination or complement-dependent cytotoxicity (CDC) are less prevalent among women with a spontaneous miscarriage, and some authors have concluded that the failure to mount a significant maternal alloimmune response could be related to pregnancy loss [5][6][7][8]. The early assumption of a protective role of humoral alloimmunity has prompted intervention studies in women with RM designed to lower the risk of future miscarriage by active immunization with paternal or third-party lymphocytes.…”

Relevance of Lunar Periodicity in Human Spontaneous Abortions

“…Since the fetus can be considered as a semiallograft, because half its MHC genes are of paternal origin, it may be recognized as non-self by the mother and consequently rejected in case of inadequate placental counteraction of maternal immunity [21].…”

Antitrophoblast antibodies are associated with recurrent miscarriages

“…T he induction of antibodies that target paternal leukocyte antigens resulting from pregnancies is a well-described immunological phenomenon in human gestation (1)(2)(3)(4)(5)(6)(7)(8).…”