Allelic Diversity and Affinity Variants of MICA Are Imbalanced in Spanish Patients With Behçet's Disease

Scand J Immunol. 2006 Jul;64(1):77-82. doi: 10.1111/j.1365-3083.2006.01780.x.

Abstract

The aetiology of Behçet's disease (BD) is still unknown, but genetic and environmental factors are involved. HLA-B*51 is considered a susceptibility marker and some MICA alleles have also been associated. Cytotoxic T lymphocytes have been suggested as responsible for BD lesions by engaging MICA through NKG2D surface molecules. In the present study, HLA-B and MICA alleles were typed by polymerase chain reaction using sequence-specific primers, in 165 healthy Spanish controls and 42 BD patients. In the healthy group, MICA*008 (28.48%), MICA*004 (17.58%), MICA*002 (14.24%) and MICA*009 (9.39%) were the predominant alleles and the most common haplotype was MICA*004-B*44 (12.12%). MICA*001 (5.15%), MICA*004, MICA*011 (4.54%) and MICA*018 (5.15%) were more frequent, and MICA*010 (1.81%) and MICA*008 were less prevalent than in other Caucasoid populations. Similar results have been reported in North African individuals and this could support the hypothesis of a common ancestral origin of both populations. The frequencies of MICA*009 and MICA*019 were significantly increased in our BD patients in comparison with controls: 22.62% versus 9.39% and 10.71% versus 1.81% respectively. The increase of MICA*019 had not been described in other BD cohorts, and it corroborates the genetic heterogeneity at MICA locus in BD patients. High-affinity MICA alleles for NKG2D were more frequent in controls than in patients. Moreover, high-affinity alleles were not found in homozygous BD patients. These results argue against the hypothesis of an autoaggressive response in BD patients through MICA-NKG2D interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Behcet Syndrome / genetics*
  • Behcet Syndrome / immunology*
  • Case-Control Studies
  • European Continental Ancestry Group
  • Gene Frequency
  • HLA-B Antigens / genetics
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • NK Cell Lectin-Like Receptor Subfamily K
  • Polymorphism, Genetic*
  • Receptors, Immunologic / immunology
  • Receptors, Natural Killer Cell
  • Spain

Substances

  • HLA-B Antigens
  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • MHC class I-related chain A
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell