Significant Compatibility Does Not Exist at the HLA‐DQB Gene Locus in Couples With Unexplained Recurrent Abortions

Takakuwa, Koichi; Higashino, Masahiko; Ueda, Hiroyuki; Yamada, Kiyoshi; Asano, Katsuaki; Yasuda, Masako; Ishii, Shiro; Kazama, Yoshiki; Tanaka, Kenichi

doi:10.1111/j.1600-0897.1992.tb00750.x

Cited by 14 publications

(10 citation statements)

References 20 publications

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“…A series of PUBMED searches were performed in order to identify all relevant studies within the period (1975–2004) that contain MESH terms, such as ‘major histocompatibility complex’, ‘human leucocyte antigen’ and ‘recurrent spontaneous abortion’ and cross‐referenced studies were obtained. A total of 42 studies were identified (17–20, 31–68). Of those, two were later excluded (38, 48), because their main objective was different from testing an effect of HLA on RSA.…”

Section: Methodsmentioning

confidence: 99%

Association of human leucocyte antigen sharing with recurrent spontaneous abortions

Beydoun

Saftlas

2005

Tissue Antigens

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An estimated 15% of clinically recognized pregnancies abort spontaneously. Recurrent spontaneous abortion (RSA) is defined as three or more consecutive miscarriages conceived with the same partner in the absence of uterine, genetic or autoimmune abnormalities. Evidence points to human leucocyte antigens (HLA) as playing a role in the successful development of the foetus. In particular, HLA compatibility is more prevalent in couples experiencing reproductive failure, especially RSA couples, compared to fertile couples. According to the immunological hypothesis, an adequate immune response is necessary for proper implantation of the embryo; conversely, a depressed response of maternal lymphocytes to the stimulation by paternal antigens because of HLA sharing can result in disorders, such as RSA. The genetic hypothesis implicates homozygosity for recessive lethal alleles in linkage disequilibrium with specific HLA haplotypes. The specificity of HLA alleles or haplotypes responsible for or linked to other RSA susceptibility genes remains unclear. In this study, we identified 40 observational studies (32 case-control, five cohort, one cross-sectional, one case series and one basic science) that examined the associations between HLA and RSA, focusing on HLA allele couple and maternal-foetal sharing, and the special role of HLA-G. We sought to identify consistent findings among studies examining similar questions. Evidence remains divided concerning the role of HLA allele couple sharing. Of major concern is the focus of many studies on couple sharing as a proxy measure of maternal-foetal sharing. Therefore, adequately powered studies are needed, which employ standard case definitions and reproducible methodologies to directly assess the role of maternal-foetal HLA sharing on the risk of RSA.

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Section: Methodsmentioning

confidence: 99%

Association of human leucocyte antigen sharing with recurrent spontaneous abortions

Beydoun

Saftlas

2005

Tissue Antigens

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“…HLA-DQA1*0505), to predispose to abortion when shared between partners (2)(3)(4). The above suggestions have not been widely accepted, given the controversial results provided by different studies (5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

14th International HLA and Immunogenetics Workshop: Report from the reproductive immunology component

et al. 2007

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The aim of the study was to investigate whether human leukocyte antigen (HLA) allele sharing between partners or the maternal killer immunoglobulin-like receptor (KIR) repertoire is associated with recurrent spontaneous abortion (RSA) and repeated implantation failure after in vitro fertilization (IVF)/embryo transfer. From a total population of 158 RSA couples, 40 couples with repeated implantation failures (IVF) and 81 control couples, reported by five different laboratories, analysis was performed for (a) HLA sharing in 50 RSA, 31 IVF and 31 control couples, (b) DQA1*0505 sharing/homozygosity among partners in 108 RSA, 40 IVF and 36 control couples, and (c) the women's KIR repertoire in 46 RSA, 26 IVF and 36 control wives. RSA couples were divided into alloimmune aborter (RSAallo) and autoimmune aborter (RSAauto). The results oppose to the suggestion that increased HLA sharing per se or a limited maternal KIR repertoire predisposes to RSA or IVF failure. However, the observation of a slightly higher percentage of DQA1*0505 sharing in the RSAauto and the IVF group needs further investigation. The ratio of inhibitory to activating KIR (actKIR) was slightly lower in RSAallo and IVF women (1.9 vs 2.6 in controls), while in a high percentage of these women, the standard receptors of the KIR A haplotype were combined with actKIR/s of the haplotype B (66.6% and 45.4% vs 20% and 15.3% in RSAauto and control groups). This may suggest a possible involvement of actKIRs in embryo implantation and the maintenance of pregnancy and also requires further investigation.

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“…In this context, there have been reports concerning the frequency and sharing of HLA antigens in couples who experienced recurrent spontaneous abortions. Recent investigations, however, demonstrated that the incidence of shared HLA antigens was not significantly higher in couples with unexplained recurrent abortions [4,5,21,27,33]. Recent investigations, however, demonstrated that the incidence of shared HLA antigens was not significantly higher in couples with unexplained recurrent abortions [4,5,21,27,33].…”

Section: Discussionmentioning

confidence: 96%

HLA-class I antigens in patients with unexplained recurrent abortion

Imai¹,

Takakuwa²,

Ishii³

et al. 2001

Journal of Perinatal Medicine

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In order to clarify the genetic background of recurrent spontaneous abortion, the frequency of HLA-A, -B, and -C alleles was analyzed in eighty-nine patients with a history of unexplained primary recurrent abortion. The frequency of each HLA-A, -B, and -C antigen allele was calculated in patients with recurrent abortion and their husbands, and compared with the frequencies in the general population represented by 207 individuals in the Niigata district of Japan. The incidence of individuals homozygous for the HLA-A, -B, and -C alleles was also compared between the patient group and the control group. The frequency of HLA-B35 in the patient group (5 of 89, 5.6%) was significantly lower than in the general population (40 of 207, 19.3%) (Odds Ratio, 0.25; 95% Confidence Interval, 0.09-0.65; P < 0.005; Pc, not significant). The frequencies of other HLA-A, -B, and -C alleles were not significantly different between the patient group and the general population. No significant difference in the frequency of HLA-A, -B, and -C alleles was observed between the husband group and the general population. The incidence of individuals homozygous for HLA-A, -B, or -C alleles in the patient group was not significantly different from the general population. The significantly lower frequency of HLA-B35 in patients with unexplained recurrent abortion suggests that the Th2-associated immune reactions may be lacking in such patients, as it has been reported that an enhanced Th2 response in conjunction with a decreased T Th1 response is a common immune reaction in HLA-B35-positive individuals.

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Significant Compatibility Does Not Exist at the HLA‐DQB Gene Locus in Couples With Unexplained Recurrent Abortions

Cited by 14 publications

References 20 publications

Association of human leucocyte antigen sharing with recurrent spontaneous abortions

Association of human leucocyte antigen sharing with recurrent spontaneous abortions

14th International HLA and Immunogenetics Workshop: Report from the reproductive immunology component

HLA-class I antigens in patients with unexplained recurrent abortion

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