KIR/HLA Gene Profile Implication in Systemic Sclerosis Patients from Mexico

Abstract

Introduction Systemic Sclerosis (SSc) is an autoimmune, inflammatory, and multisystemic disease characterized by the presence of autoantibodies and fibrosis. The pathogenesis involves the interaction between immune system cells such as macrophages, NK cells, T cells, and B cells. Killer-cell Immunoglobulin-like Receptors (KIR) are expressed in NK cells and some T cell subsets that recognize HLA class I molecules as ligands and are involved in regulating the activation and inhibition of these cells. The KIR family consists of 14 genes and two pseudogenes; according to the gene content, the genotype could be AA and Bx. The aim of this study was to evaluate the association between KIR/HLA genes and genotypes with SSc and the clinical characteristics. Methods We included 50 SSc patients and 90 Control Subjects (CS). Genotyping of KIR, HLA-C, -Bw4, and -A∗03/∗11 was made by SSP-PCR. Results In SSc patients, a higher frequency of KIR2DL2 (p = 0.0007, p′ = 0.011), KIR2DS4del (p = 0.001, p′ = 0.021), and HLA-C2 (p = 0.02, p′ = 0.09) was found. This is the first study to evaluate the frequency of HLA-A∗03/∗11 in SSc patients, of which a low frequency was found in both groups. Compound genotypes KIR2DL2+/HLA-C1+ or KIR2DL2+/HLA-C2+ have a higher frequency in SSc patients. The Bx genotype was the most frequent and was associated with risk to SSc (p = 0.007, OR = 3.1, 95% CI = 1.4–7.9, p′ = 0.014). The genotypes with a higher iKIR number than aKIR (iKIR > aKIR) were found in all individuals; genotypes with 7-8 iKIR genes were increased in SSc patients. We do not find an association between the KIR genes with the clinical characteristics. Conclusion The results suggest that KIR2DL2 and 2DS4del could have a risk role in the development of SSc, but not with clinical manifestations.

Diversity of KIR/HLA Genotypes and Their Association with Psoriasis Vulgaris in the Western Mexican Population

“…The Bx and AA genotype frequencies found in this study agreed with previous reports from our population [27,28]. Studies in autoimmune diseases, such as type 1 diabetes, systemic sclerosis, rheumatoid vasculitis, and rheumatoid arthritis, have shown an increased frequency of Bx genotypes in patients compared to the control group, which could be since that Bx genotypes, compared to AA genotypes, usually contain a greater number of genes that encode activating receptors, including KIR3DS1 [27,33,34].…”

Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk

“…The B -haplotype KIR s were correlated with an increased risk of other solid and hematological malignancies, including leukemia 51 , cervical neoplasia 52 , Hodgkin lymphoma 53 , gastric cancer 54 , head and neck squamous cell carcinoma 55 , urothelial bladder cancer 56 , colorectal adenocarcinoma 57 , systemic sclerosis 58 , and meningioma 59 . The B haplotype-specific KIR s, particularly those located at the telomeric half ( 3DS1, 2DS1, and 2DS5 ), were observed to be prominently increased in patients with an advanced stage of breast cancer.…”

Evaluation of the association between KIR polymorphisms and systemic sclerosis: a meta-analysis

“…The initial search resulted in 19 related studies. Based on exclusion/inclusion criteria, 5 articles with 571 patients and 796 healthy participants were included in the final metaanalysis [15,[28][29][30][31]. All included papers were casecontrol studies.…”