Association of killer cell immunoglobulin-like receptor and human leucocyte antigen-Cw gene combinations with systemic lupus erythematosus

Clin Exp Immunol. 2015 May;180(2):250-4. doi: 10.1111/cei.12582.

Abstract

Killer cell immunoglobulin-like receptors (KIRs) are a diverse family of activating and inhibitory receptors expressed on natural killer (NK) cells and T cells, the genes of which show extreme polymorphism. Some KIRs bind to human leucocyte antigen (HLA) class I subgroups, and genetic interactions between KIR genes and their ligand HLA have been shown to be associated with several autoimmune diseases. The present study aimed to investigate whether the combinations of KIR genes and HLA-Cw ligands associate with the susceptibility of systemic lupus erythematosus (SLE). Polymerase chain reaction using sequence-specific primers was used to determine the genotypes of KIR genes and HLA-Cw alleles. We found that the frequencies of HLA-Cw07 were statistically significantly higher in the patient group than those in the control group (P = 0·009). KIR2DS1(+) HLA(-) Cw(Lys) was more common in subjects with SLE compared to control subjects (P = 0·015). In addition, the frequency of KIR2DS1 was increased in SLE when KIR2DL1/HLA-Cw are absent, and the difference was significant (P = 0·001). KIR genotype and HLA ligand interaction may potentially influence the threshold for NK (and/or T) cell activation mediated through activating receptors, thereby contributing to the pathogenesis of SLE.

Keywords: genes; killer cell immunoglobulin-like receptors; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Female
  • Gene Frequency*
  • Genotype
  • HLA-C Antigens / genetics*
  • HLA-C Antigens / immunology
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / pathology
  • Lymphocyte Activation / genetics
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Receptors, KIR / genetics*
  • Receptors, KIR / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology

Substances

  • HLA-C Antigens
  • HLA-C*70 antigen
  • KIR2DS1 protein, human
  • Receptors, KIR