Major histocompatibility complex antigens, maternal and paternal immune responses, and chronic habitual abortions in humans

Beer, Alan E.; Quebbeman, James F.; Ayers, Jonathan W.T.; Haines, Richard F.

doi:10.1016/s0002-9378(16)32690-4

Cited by 314 publications

(43 citation statements)

References 15 publications

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“…[4] The reports on antigen sharing in couples with recurrent miscarriage led to several studies assessing the role of HLA antigens and their influence on the outcome of pregnancy. [27] In fact, couples sharing at HLA A, HLA B, HLA C, HLA DR, and HLA DQ loci has been reported to be positively associated with the risk of RSA. [28] Since 1977, increased HLA sharing among spouses has been associated with RSAs; later more specific HLA DR and/or DQ antigens were suggested.…”

Section: Discussionmentioning

confidence: 99%

HLA allele associations in idiopathic recurrent spontaneous abortion patients from India

Shankarkumar¹,

Pawar²,

Gaonkar³

et al. 2008

J Hum Reprod Sci

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BACKGROUND:Rejection of semiallogenic foetus in recurrent spontaneous abortion (RSA) has been postulated to be a consequence of genetic and immunological phenomena.AIM:To evaluate the role of human leukocyte antigen (HLA) alleles in RSA in Indian couples.SETTINGS AND DESIGN:A case-control study.MATERIALS AND METHODS:Eighty-one randomly selected couples with unexplained three or more RSAs and a control group of 97 couples with live birth belonging to the same ethnic background, referred to the Gynaecology Department, KEM Hospital were included in the case-control study. Serological HLA A and B typing was done followed by molecular subtypes, defined using PCR-SSOP technique for HLA A, B, and C in 40 couples and DRB1* and DQB1* in 28 couples which were then compared with appropriate case 46 and 88 controls.RESULTS:Serologically A3 (15.43% vs. 4.43%; odds ratio (OR) = 4.34; P = 0.0002) and B17 (25.3% vs. 11.34%; OR = 3.49; P = 0.0001) were increased. Haplotype A1-B17 was significantly increased. Molecular subtyping revealed that A*030102 (11.25% vs. 4.34%; OR = 3.00; P = 0.07), B*5701 (11.25% vs. 1.08%; OR = 13.10; P = 0.003), Cw*120201 (25% vs. 4.34%; OR = 10.50; P = 2.05E-05), HLA DRB1*030101 (17.85% vs. 3.40%; OR = 7.6; P = 0.0001), DRB1*150101 (32.14% vs. 13.63%; OR = 4.8; P = 0.0003), and DQB1*060101 (35.71% vs. 29.34%; OR = 2.3; P = 0.004) were significantly increased in patients. A differential association was noticed when compared with reported world RSA patients.CONCLUSION:The HLA alleles A*030101, B*5701, Cw*120201, DRB1*030101, and DRB1*150101 as well as their associated ancestral haplotype may play a significant role in development of RSA in India.

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Section: Discussionmentioning

confidence: 99%

HLA allele associations in idiopathic recurrent spontaneous abortion patients from India

Shankarkumar¹,

Pawar²,

Gaonkar³

et al. 2008

J Hum Reprod Sci

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“…Similar effects may be associated with the presence of antisperm antibodies in infertile human couples (1). Immunologic factors have also been implicated in the occurrence of spontaneous abortions in some women (27). Auto-and iso-antibodies against the 63-kDa antigen, which is found in human sperm, may be of significance in some couples with unexplained infertility, especially those negative by the conventional sperm immobilization and agglutination techniques.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a membrane antigen from rabbit testis and sperm isolated by using monoclonal antibodies and effect of its antiserum on fertility.

Naz¹,

Rosenblum²,

Menge³

1984

Proc. Natl. Acad. Sci. U.S.A.

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An antigen was isolated from deoxycholatesolubilized rabbit testis and sperm by using an immunosorbent column containing IgG from a monoclonal antibody (8C10.5) that inhibits fertility. Elution was by stepwise increases in pH (8.0, 10.0, and 11.4), with the pH 11.4 fraction after recycling through the column showing a single band at 63 kilodaltons in slab NaDodSO4/PAGE with a silver stain. The antigen molecule was composed of two subunits, which on two-dimensional PAGE showed many spots within the same molecular size range (50-70 kilodaltons) but differing in charge. The antigen isolated either from testis or sperm showed mainly the same spots. The antigen is periodic acid/Schiff positive and contained 21% carbohydrate. An asialo-derivative of the antigen did not change its characteristics on NaDodSO4/PAGE. This glycoprotein resolved into two types of polypeptides, those binding and those not binding to a lens culinaris lectin column; some of the polypeptides appeared common to both fractions. Murine antiserum against the antigen neither agglutinated nor immobilized rabbit sperm but in immunofluorescence reacted with the plasma membrane of viable rabbit sperm as well as with murine and human sperm. Fertilization offemale rabbits inseminated with treated sperm was not affected, but, by 9 days, fertility was significantly reduced (21% of controls). The postfertilization antifertility effect was not due to parthenogenic activation or to polyspermy. The antiserum reacted with one specific band in the one-and two-dimensional gel electrophoretic transfer blot procedure and was unaffected by absorption with different somatic tissues.Antigenicity of sperm cells has been well documented and implicated in involuntary immunological infertility in human couples (1). Experimentally, female animals immunized with preparations of isologous sperm or testis have reduced fertility (2, 3). However, use of whole sperm or testicular homogenate is undesirable because of the presence of some antigens shared with somatic tissues. Recently, attempts have been made to isolate and purify biochemically different antigens from sperm and testes and to investigate their immunologic effect on reproduction in female animals. Immunization with testis-specific lactate dehydrogenase (LDH-C4) purified from mouse testes has been shown to reduce fertility in mice, rabbits, and baboons (4). In spite of the use of strong potentially toxic adjuvants like complete Freund's adjuvant, which are nonpermissible for humans, fertility has been reduced but not completely blocked. Acrosin and hyaluronidase, enzymes purified from the acrosomes of sperm and involved in the fertilization process (5), have proved to be less than promising candidates for a potential antipregnancy vaccine (6, 7). Antisera against a plasma membrane antigen (RSA-1) isolated from rabbit sperm and testes reduced but did not completely block fertility in females upon artificial insemination of treated sperm (8).Attempts are being made to develop new diagnostic methods for immunoinf...

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“…Immunopotentiation was first reported as a means of preventing abortion by Beer et al [3] and Taylor and Faulk [19] in 1981. These early reports were based on the assumption that the habitually aborting woman is either hyporesponsive or has an aberrant immune response to the paternal antigens presented to her by the pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Selection of patients with habitual abortion for paternal leucocyte immunization

Carp

Toder

Gazit

et al. 1990

Arch Gynecol Obstet

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After potentiation of the immune response in habitual aborters 75-85% of subsequent pregnancies are claimed to result in healthy term infants. However, all publications to date have either been based on the authors concept of the immune processes involved or an attempt to demonstrate the efficacy of treatment either empirically or by matched trials. As immunization is coming into wider clinical use, it is necessary to determine which patients will benefit from this form of treatment. This paper presents our experience with paternal leucocyte immunization over the period 1985-1988. 207 patients were classified on a clinical basis and by immunological testing. 143 patients have been immunised, 129 pregnancies have occurred in 108 patients. The vast majority of our patients have recurrent missed abortions. Only six women habitually aborted live fetuses. Two had subsequent live births. Secondary aborters seem to do well in subsequent pregnancies, whether immunized or not. The patient most likely to benefit from immunization is the Primary missed aborter who does not possess antipaternal antibody (APCA), but is induced to produce APCA by immunization. Using these criteria, 75% success rates are observed in the subsequent pregnancy. This success rate is irrespective of HLA antigen sharing or in-vitro mixed lymphocyte reactivity.

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Major histocompatibility complex antigens, maternal and paternal immune responses, and chronic habitual abortions in humans

Cited by 314 publications

References 15 publications

HLA allele associations in idiopathic recurrent spontaneous abortion patients from India

HLA allele associations in idiopathic recurrent spontaneous abortion patients from India

Characterization of a membrane antigen from rabbit testis and sperm isolated by using monoclonal antibodies and effect of its antiserum on fertility.

Selection of patients with habitual abortion for paternal leucocyte immunization

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