Association of CD94/NKG2A, CD94/NKG2C, and its ligand HLA‐E polymorphisms with Behcet’s disease

Abstract

Inhibitory CD94/NKG2A and activating CD94/NKG2C receptors are expressed on natural killer, CD4, and CD8 T cells and recognize human leukocyte antigen (HLA)-E, resulting in the modulation of cytotoxic activity and cytokine production. An imbalance in cytotoxic activity and cytokine production has been implicated in Behcet's disease (BD). The results of this study showed that the NKG2A c.-4258*C, c.338-90*G, and CD94 c.-134*T alleles (P ¼ 0.015, OR ¼ 0.8; P < 0.0001, OR ¼ 0.5; and P ¼ 0.034, OR ¼ 0.8, respectively) were associated with decreased risk and that NKG2A c.284-67_-62del, c.1077*C, and the activating receptor, NKG2C c.305*T were not associated with 345 patients with BD. But a significant difference in NKG2C c.305*T was detected among BD patients with ocular lesions and arthritis (P < 0.0001, OR ¼ 2.1 and P ¼ 0.0001, OR ¼ 1.8, respectively). We already showed in our previous research that HLA-E*0101 also appears to contribute to a reduction in risk through the inhibitory CD94/NKG2A-mediated immune response. This result led us to the analyses of the combined risk of the HLA-E and the NKG2A for BD. Individuals harboring HLA-E*0101, NKG2A c.-4258*C, and c.338-90*G evidenced a reduced risk of BD compared with healthy controls (21.1% vs 40.1%, P < 0.0001, OR ¼ 0.4).

Polymorphisms within the human leucocyte antigen-E gene and their associations with susceptibility to rheumatoid arthritis as well as clinical outcome of anti-tumour necrosis factor therapy

“…The role of the HLA-E in the development of autoimmunity is supported by several studies. The HLA-E*01:03/ 01:03 genotype has been associated with increased risk of Behc¸et's disease (BD) [18]. Moreover, this genotype was found to be a risk factor for pemphigus vulgaris (PV) development [20].…”

Clinical Significance of the HLA-E and CD94/NKG2 Interaction

“…Though no variation was detected in coding regions of CD94 gene, it has SNP at position c. (Hikami et al 2003;Park et al 2008;Seo et al 2007).…”

“…The NKG2A SNPs c. -4258*C and c. 338-90*G, as well as the CD94 SNP c. -134*T were connected with decreased risk of Behçet's disease (Seo et al 2007). Moreover, the NKG2A c. 338-90*AA, NKG2C 102 Ser/ Ser, and NKG2D 72*Ala/Ala were significantly correlated Activating and inhibitory signal transduction and regulation in NK cells or CTLs.…”

Association of HLA-E*01:01/*01:03 polymorphism with methotrexate-based treatment response in South Indian rheumatoid arthritis patients

“…HLA-E rs1264457 dimorphism at position 107 resulting in differential expression of HLA-E (E*01:01 and E*01:03) alleles on cell surface is reported to have important clinical implications for immune mediated disorders through its role as a regulatory molecule and its interaction with NK cell receptors. 5,15,16,25 There is paucity of data on the role of HLA-E polymorphism in inflammatory arthritides. The only study published till date is from Sardinia, which reported its low expressor variant (HLA-E*01:01) to be associated with ankylosing spondylitis.…”