Maternal killer-cell immunoglobulin-like receptors and paternal human leukocyte antigen ligands in recurrent pregnancy loss cases in Turkey

Abstract

Objective: The survival of a semi-allogeneic fetus depends on several immunological mechanisms, and it has been suggested that recurrent pregnancy loss (RPL) could develop as a result of one or more immunological abnormalities.Methods: Compatibility between partners for human leukocyte antigen (HLA) genotypes and the relationships between maternal killer-cell immunoglobulin-like receptor (KIR) and paternal HLA-Bw4/Bw6 and HLA-C1/C2 supra-groups were investigated in 25 couples with RPL in comparison to healthy couples with children. HLA and KIR genotyping was performed using polymerase chain reaction with sequence-specific primers and/or sequence-specific oligonucleotides.Results: HLA class I incompatibility between partners, especially in HLA-B alleles, was more common in the RPL group (<i>p</i>= 0.01). HLA-C2 homozygosity was more frequent in the male partners of RPL couples than in other groups (<i>p</i>= 0.03). The <i>KIR2DL5</i> gene frequency was significantly higher in both the female and male partners of RPL couples, whereas the <i>KIR2DS3</i> gene frequency in male partners of RPL couples was significantly reduced (<i>p</i>= 0.03). The presence of KIR2DL3 in women with RPL was correlated with the presence of HLA-C2 alleles in their spouses (<i>p</i>= 0.03).Conclusion: Our data from a Turkish population suggest that male HLA-C2 homozygosity may play an important role in RPL. Additionally, an incidental match between male HLA-C2 and female HLA-C1 ligand KIR receptors might perturb the balance between activatory and inhibitory KIR-ligand interactions during pregnancy in couples affected by RPL. The roles of orphan <i>KIR2DL5</i> and orphan <i>KIR2DS3</i> in RPL remain obscure.

Killer‑cell immunoglobulin‑like receptor/human leukocyte antigen‑C combination and ‘great obstetrical syndromes’ (Review)

“…Amidst these, the etiology of certain patients is unknown and may be related to autoimmune abnormalities. The correlation between KIR/HLA-C combination and RPL is listed in Table I, a few are inconsistent (14)(15)(16)(17)19,25,26,(59)(60)(61)(62)(63)(64)(65). Reportedly, RPL females had an elevated rate of maternal KIR AA haplotype and fetal HLA-C2 binding (14,15,60,66).…”

“…HLA-C1 is the ligand for KIR2DL2. Compared with healthy females, RPL patients exhibited higher KIR2DL2 and HLA-C2/C2 or HLA-C2/x combinations ( 65 ). Initially, the authors established that KIRs in partners could not directly result in a miscarriage; however, since the fetal KIR genotype is unclear, distributed fetal cells with potentially unfavorable KIRs can accelerate the ending course ( 65 ).…”

“…Compared with healthy females, RPL patients exhibited higher KIR2DL2 and HLA-C2/C2 or HLA-C2/x combinations ( 65 ). Initially, the authors established that KIRs in partners could not directly result in a miscarriage; however, since the fetal KIR genotype is unclear, distributed fetal cells with potentially unfavorable KIRs can accelerate the ending course ( 65 ). It was recently reported that KIR2DL2-positive RPL females exhibited decreased molecules of HLA-C1 compared with KIR2DL2-negative RPL females (P<0.05) ( 26 ).…”