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MICA and NKG2D variants as risk factors in spondyloarthritis: a case-control study

Abstract : The major histocompatibility complex class I polypeptide-related sequence A (MICA) glycoprotein mediates the activation of the natural killer group 2D receptor (NKG2D) expressed on NK and CD8+ T cells. A methionine or valine at position 129 in exon 3 results in strong (MICA129 met) or weak (MICA129 val) binding to NKG2D. The MICA A5.1 allele causes a premature stop codon. Various NKG2D polymorphisms are associated with low (NKC3 C/C and NKC4 C/C) or high (NKC3 G/G and NKC4 T/T) levels of NK cell cytotoxic activity. In 162 patients with spondyloarthritis (115 with ankylosing spondyloarthritis, 46 with psoriatic arthritis and 1 with reactive arthritis) compared to 124 healthy controls, MICA-129 with methionine allele was more frequent in patients with spondyloarthritis (odds ratio (OR) (95% confidence interval) = 4.84 (2.75-8.67)), whereas MICA-129 val/val, MICA A5.1 and NKC3 C/C variants were less frequent (OR = 0.20 (0.11-0.37), 0.15 (0.06-0.36) and 0.24 (0.13-0.44), respectively). After adjustment for HLA-B*27 status, only NKC3 C/C remained linked to spondyloarthritis (adjusted OR = 0.14 (0.06-0.33)). Homozygosity for MICA A5.1 is linked to ankylosing spondyloarthritis, and NKC3 C/C and MICA-129 val/val to psoriatic arthritis. MICA and NKC3 polymorphisms (related to a low NK cell cytotoxic activity) constituted a genetic association with spondyloarthritis.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03591571
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Soumis le : lundi 28 février 2022 - 16:38:50
Dernière modification le : jeudi 7 avril 2022 - 13:58:15

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Marie Fechtenbaum, Judith Desoutter, Gauthier Delvallez, Etienne Brochot, Nicolas Guillaume, et al.. MICA and NKG2D variants as risk factors in spondyloarthritis: a case-control study. Genes and Immunity, Nature Publishing Group: Open Access Hybrid Model Option B, 2019, 20 (7), pp.599-605. ⟨10.1038/s41435-018-0044-x⟩. ⟨hal-03591571⟩

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