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.

MICA polymorphisms and decreased expression of the MICA receptor NKG2D contribute to idiopathic pulmonary fibrosis susceptibility

“…Frequency of high and reduced NKG2D binding aYnity MICA alleles Functional comparisons have demonstrated important diVerences in the NKG2D binding aYnity of diVerent MICA alleles (Steinle et al 2001;Muñoz-Saá et al 2005). Thus, studies using soluble NKG2D showed that substitution of valine 129 by methionine confer high NKG2D binding aYnity while reduction in aYnity is observed when methionine 129 is replaced by valine (Steinle et al 2001).…”

“…Alleles with valine 129 and reduced aYnity are MICA*004, *006, *008, *009, *010, *016, *019. Alleles with methionine 129 and high aYnity are MICA*001, *002, *007, *011, *012, *015, *017, *018, *021 (Steinle et al 2001;Muñoz-Saá et al 2005).…”

Adenovirus E3/19K Promotes Evasion of NK Cell Recognition by Intracellular Sequestration of the NKG2D Ligands Major Histocompatibility Complex Class I Chain-Related Proteins A and B

“…E3/19K targets both MICA and MICB with similar efficiency and does not affect ULBP1 to -3 (data not shown), whereas UL16 does not target MICA or HLA-I. E3/19K thus has a novel function in being able to target a broad range of MICA and MICB alleles; in particular, it can target the MICA*008 allele, which is the most commonly expressed allele in populations studied to date (35,38). It has been speculated that the MICA*008 allele may have emerged as a result of the host response to viral evasion functions acting on MICA (53).…”

Procoagulant microparticles are increased in patients with Behçet’s disease but do not define a specific subset of clinical manifestations

“…Cerebrovascular ischemic episodes were confirmed by computed tomography scanning or by magnetic resonance imaging techniques. Some of patients of the present series have been included in previous studies [6,15,16]. The main cumulative clinical characteristics and previous and current treatments of these patients are described in Table 1.…”

“…The mean (SD) age at onset of the disease was 27 (12)years (range, 10 to 58). The mean age at diagnosis was 31 (13)years (range, 16 to 62), and the mean age at study inclusion was 35 (15) years (range, 16 to 67). Median follow-up was 36 months (range, 1 to 276).…”