Significance of inhibitory maternal killer-cell immunoglobulin-like receptor (KIR) and fetal KIR ligand genotype combinations in placenta related obstetric complications

• Published in: Journal of reproductive immunology 2021-11, Vol.148, p.103425-103425, Article 103425
• Main Authors: Orgul, Gokcen, Dalva, Klara, Dalva-Aydemir, Sevim, Alniacik, Ridvan Goksel, Donmez, Hanife Guler, Cakar, Ayse Nur, Beksac, Meral, Beksac, Mehmet Sinan
• Format: Article
• Language: English
• Subjects: Abortion, Habitual - immunology; Adult; Delivery, Obstetric; Female; Fetus - metabolism; Genotype; HLA-C Antigens - genetics; HLA-C Antigens - metabolism; Humans; Killer cell immunoglobulin like receptor; Killer Cells, Natural - immunology; Major histocompatibility complex Class-I antigen; Miscarriage; Natural killer cell; Obstetric complication; Placenta - metabolism; Placenta - pathology; Placental inflammation; Pre-Eclampsia - immunology; Pregnancy; Premature Birth - immunology; Receptors, KIR2DL3 - genetics; Receptors, KIR2DL3 - metabolism
• ISSN: 0165-0378; 1872-7603
• DOI: 10.1016/j.jri.2021.103425

•Physiological placentation necessitates accomplished interaction between KIR/KIR ligands.•Inhibitory 2DL3-C1 and 3DL1-Bw4 were more frequent in placenta-related obstetric complications.•Less fetal HLA-C2 homozygosity was observed in placenta-related obstetric complications. Some maternal killer-cell immunoglobulin-like receptor (KIR) and fetal KIR ligand genotypes are associated with obstetric complications, such as recurrent miscarriage, fetal growth restriction, preeclampsia, and preterm birth. However, how KIR/KIR ligand genotypes affect these placenta-related obstetric complications has not been fully understood. We aimed to demonstrate the association of maternal KIR-fetal KIR ligand genotype combinations with immunological/metabolic risk factor associated placenta-related obstetric complications. This study consisted of three groups of pregnant women: 1) Miscarriage group (n = 30), 2) Complicated Pregnancy (CP) group (n = 30), and 3) Control group (n = 30). The observed maternal genotype frequencies of all inhibitory and activating KIRs were similar in all groups (p > 0.05). However, inhibitory 2DL3 was quite frequent in the miscarriage group (p = 0.052). There was no difference between groups in terms of centromeric and telomeric maternal haplotypes (p > 0.05). The fetal group 1 HLA-C genotype was frequently detected in the miscarriage and CP groups with rates of 83.3 % and 93.3 % respectively, while the observed frequency was 70 % in the control group. The fetal group 2 HLA-C genotype was the same in all groups. The results demonstrated significantly less fetal group 2 HLA-C homozygosity in the CP groups when compared to the control group (p = 0.020). The fetal HLA-Bw4 genotype was detected more frequently in the miscarriage and CP groups (p = 0.028 and p = 0.001, respectively). The inhibitory KIR/KIR ligand genotype combinations of 2DL3-C1 and 3DL1-Bw4 were more frequent in the miscarriage and CP groups (p = 0.045 and p = 0.002, respectively). Enhanced NK cell inhibition may be one of the mechanisms underlying placenta-related obstetric complications.