title: Allelic diversity and affinity variants of MICA are imbalanced in Spanish patients with Behçet's disease.
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.
authors.affiliation: Immunology Service, Hospital Universitari Son Dureta, Palma de Mallorca, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Muñoz-Saá
authors.forename: A
authors.initials: A
authors.lastname: Cambra
authors.forename: L
authors.initials: L
authors.lastname: Pallarés
authors.forename: G
authors.initials: G
authors.lastname: Espinosa
authors.forename: A
authors.initials: A
authors.lastname: Juan
authors.forename: F
authors.initials: F
authors.lastname: Pujalte
authors.forename: N
authors.initials: N
authors.lastname: Matamoros
authors.forename: J
authors.initials: J
authors.lastname: Milà
authors.forename: M R
authors.initials: MR
authors.lastname: Julià
mesh_terms: D001528:Behcet Syndrome / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D005787:Gene Frequency; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D013030:Spain; D044465:White People
chemical_list: D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell