Analysis of HLA‐DR types of unexplained recurrent spontaneous aborters in the Japanese population by oligonucleotide‐DNA typing

Abstract

To examine whether unexplained recurrent spontaneous abortion (URSA), defined as 2 or more consecutive spontaneous abortions, is correlated with a particular DR type in the Japanese population, we determined the HLA-DR types of 82 primary aborters and 21 secondary aborters by DNA typing utilizing the polymerase chain reaction (PCR) and hybridization with sequence-specific oligonucleotides (SSOs). The DR gene frequencies of the patient group were compared with those of a normal group at three different levels of DR-definition (27, 13 and 11 DR types). At none of the three levels of comparison was any particular DR type with a frequency differing significantly between the patient and normal groups detected in Japanese URSA patients. Furthermore, we examined whether URSA was correlated with the degree of compatibility of HLA-DR antigen within patients and their husbands. Comparison of the DR compatibility between patients and normal couples was made in two different ways, i.e., comparison of the numbers of couples with mismatches and comparison of the average number of mismatches. For either of these two comparisons, we observed no difference in DR compatibility between patients and normal couples. Our results suggest that URSA is not correlated with any particular DR type and that the condition cannot be explained simply by DR compatibility between husband and wife.

Association of human leucocyte antigen sharing with recurrent spontaneous abortions

“…At least three studies identified couples at risk of RSA, if they shared alleles at any of a number of HLA loci (16, 39, 53), and one reported an increased risk among couples who shared the entire 16‐loci HLA haplotype (61). By contrast, other studies have failed to identify a relation between RSA and couple sharing at HLA‐A (17–19, 27, 33, 35, 36, 46, 49–52, 54, 55), HLA‐B (18, 19, 27, 33, 35–37, 46, 49–52, 54, 55), HLA‐C (18, 49, 54), HLA‐DR (19, 27, 33, 35, 37, 46, 49–52, 54–56) or HLA‐DQ (57) (Table 1).…”

“…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.…”

“…Of the 40 selected studies, the vast majority had adopted a case‐control design, five a cohort approach (27, 32, 61, 64, 66), one was cross‐sectional (19), another was a case series (34) and one had a basic sciences (65) design. Most studies reviewed in this study examined couple sharing (16–19, 27, 31–37, 39–42, 44–47, 49–57, 59–61), three were concerned with maternal–foetal sharing of HLA genotype (19, 58, 59) and nine relatively recent studies examined HLA‐G characteristics (20, 60, 62–68) as potential risk factors for RSA.…”

Human reproductive failure II: Immunogenetic and interacting factors

“…Studies often differ in the selection and strati®cation of fertile and RSA couples. Interestingly, recent studies based upon DNA techniques have not detected increased class II nor class I parental sharing in RSA couples (Christiansen et al, 1989;Ito et al, 1992;Takakuwa et al, 1992;Laitinen et al, 1993;Karhukorpi et al, 1997;Wagenknecht et al, 1997;Yamashita et al, 1999). Intermittent associations between parental HLA sharing and reproductive failure may re¯ect linkage disequilibrium in some outbred populations.…”

“…Thus, differences in methodology and reliability can confound attempts to compare data concerning HLA sharing between published studies (Wagenknecht et al, 1997). The majority of recent studies, using DNA-based techniques, have not detected increased sharing of HLA-DR and/or -DQ alleles in couples with RSA (Christiansen et al, 1989;Ito et al, 1992;Takakuwa et al, 1992;Laitinen et al, 1993;Wagenknecht et al, 1997). Increased HLA-G (Karhukorpi et al, 1997;Yamashita et al, 1999) or HLA-C sharing among couples with recurrent miscarriage has not been observed either (Christiansen, 1999).…”