Association of Maternal Histocompatibility at Class II HLA Loci with Maternal Microchimerism in the Fetus

Abstract

For investigating the possible influence of maternal-fetal HLA compatibility on maternal microchimerism, DNA samples from blood of 120 maternal-fetal pairs were genotyped at two polymorphic loci: glutathione-S-transferase M1 (GSTM1) and angiotensin-converting enzyme (ACE). Informative pairs (mother heterozygous/fetus homozygous at one of the two loci) were then tested by quantitative real-time PCR for the noninherited maternal allele(s) and genotyped at the HLA-A, B, and C class I loci and/or at the DRB1 and/or DQB1 class II loci. Small numbers of maternal cells were detected in the circulation of 16 of the 30 informative second-and third-trimester fetuses. Comparison with HLA data suggested an association between microchimerism and maternal compatibility at the class II DRB1 and/or DQB1 HLA loci and with the maternal HLA-DQB1*0301 allele. There was no relationship between maternal microchimerism and maternal-fetal HLA compatibility at other HLA loci or with gestational age, fetal anomalies, or red cell or platelet isoimmunity. Transplacental passage of small numbers of maternal and fetal nucleated cells, including hematopoietic stem cells, is a common occurrence that often results in persistent fetal or maternal microchimerism-the presence of small numbers of fetal or maternal cells in mothers or their progeny, respectively (1-3). This raises the possibility that maternal and fetal microchimerism may play a role in such clinically important phenomena as immune ontogeny, vertical transmission of infections, and tissue repair and regeneration by transdifferentiated stem cells. Particular interest has focused on the possibility that chimeric maternal and fetal alloreactive lymphocytes may play a role in autoimmunity (4 -6). Although an increasing number of clinical studies have addressed this question, there has been a paucity of information concerning the factors that regulate the presence and levels of naturally occurring maternal and fetal chimeric cells.Among the possible regulatory factors that might be involved, maternal-fetal histocompatibility seems to be a prime candidate in view of the importance of histocompatibility in regulating hematopoietic chimerism in both adult and fetal recipients of adult bone marrow. In this study, we directly tested for the first time the influence of maternal-fetal histocompatibility and specific HLA alleles on both the presence and level of maternal microchimerism in the fetus. The results strongly suggest that maternal microchimerism in fetal blood is associated with maternal compatibility at the class II DRB1 and/or DQB1 HLA loci and is likely also associated with the maternal HLA-DQB1*0301 allele. METHODSStudy subjects. Paired whole-blood samples were obtained from 120 maternal-fetal pairs who underwent fetal blood sampling for a variety of medical indications, including red cell or platelet alloimmunization, and the need for rapid karyotyping mandated by an ultrasound diagnosis of fetal anomalies. The gestational age at fetal blood sampling ranged from 18.3 wk to 38 wk ...

Maternal HLA class II compatibility in men with systemic lupus erythematosus

“…One possibility is that such compatibility occurs through maternal microchimerism, but an alternative theory is that maternal HLA molecules could affect a child's immune system in utero by influencing T cell development. Whether HLA compatibility affects persistence or levels of maternal microchimerism later in life is not known, although results of a small study suggested an increase in maternal microchimerism in the context of HLA class II compatibility (12). As suggested in studies of dermatomyositis (13), one consideration is that maternal microchimerism might affect a mother's progeny through anti-fetal alloreactive T cell responses.…”

Fetal Microchimerism in Cancer Protection and Promotion: Current Understanding in Dogs and the Implications for Human Health

“…Evidence exists that chimerism is more likely with maternal haploidentical cells than with mismatched haplotype cells [62]. However, tolerization of mismatched cells is described [63].…”

Microchimérisme postgestationnel en pathologie humaine

“…Des études ultérieures utilisant des échantillons de sang foetal provenant de cordocentèses au 2 e et 3 e trimestre de la grossesse ont retrouvé des résultats similaires, permettant d'exclure la possibilité d'une contamination par du sang maternel au moment du prélèvement [44,45]. D'autres études ont également suggéré que le microchimé-risme maternel se développait durant la vie foetale [46,47]. Le transfert maternofoetal a ainsi été mis en évidence précoce-ment, dès la 13 e SA.…”