Killer immunoglobulin‐like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease

López-Hernández, Ruth; Campillo, José A.; Legáz, Isabel; Valdés, Mariano; Salama, Hortensia; Boix, Francisco; Hernández-Martínez, AM; Eguía, Jorge; González-Martínez, Gema; Moya‐Quiles, María Rosa; Minguela, Alfredo; García‐Alonso, Ana M.; Carballo, Fernando; Muro, Manuel

doi:10.1111/1348-0421.12447

Cited by 10 publications

(7 citation statements)

References 26 publications

(44 reference statements)

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“…This reaction produces a color signal that is detected by the analyzer Luminex. Analysis of all signals from the responding probes in special program allows to obtain the result of KIR genotyping on intermediate resolution ( Figure 5 ) [ 38 , 39 ].…”

Section: Kir Typing Methodsmentioning

confidence: 99%

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

Dębska-Zielkowska

Moszkowska

Zieliński

et al. 2021

Cells

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Natural killer (NK) cells are part of the cellular immune response. They target mainly cancer and virally infected cells. To a high extent cytotoxic activity of NK cells is regulated inter alia by signals from killer immunoglobulin-like receptors (KIR). The major histocompatibility complex (MHC) class I molecules are important ligands for KIR receptors. Binding of ligands (such as MHC I) to the KIR receptors has the important role in solid organ or hematopoietic cell transplantation. Of note, the understanding of the relationship between KIR and MHC receptors may contribute to the improvement of transplant results. Donor-recipient matching, which also includes the KIR typing, may improve monitoring, individualize the treatment and allow for predicting possible effects after transplantation, such as the graft-versus-leukemia effect (GvL) or viral re-infection. There are also less evident implications of KIR/MHC matching, such as with pregnancy and cancer. In this review, we present the most relevant literature reports on the importance of the KIR/MHC relationship on NK cell activity and hematopoietic stem cell transplantation (HSCT)/solid organ transplantation (SOT) effects, the risk of allograft rejection, protection against post-transplant cytomegalovirus (CMV) infection, pregnancy complications, cancer and adoptive therapy with NK cells.

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Section: Kir Typing Methodsmentioning

confidence: 99%

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

Dębska-Zielkowska

Moszkowska

Zieliński

et al. 2021

Cells

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“…Among inhibitory KIRs, KIR2DL1 recognizes group 2 HLA-C (HLA-C2) molecules, which have lysine at position 80, KIR2DL2 and KIR2DL3 recognize group 1 HLA-C (HLA-C1) having asparagine at position 80, and KIR3DL1 recognizes HLA-Bw4 [ 2 – 6 ]. Although several studies have demonstrated that KIR-HLA receptor-ligand combinations are associated with IBD [ 7 – 12 ], discrepancies in the literature exist. KIR genes have not been evaluated in Japan to date.…”

Section: Introductionmentioning

confidence: 99%

Association between KIR-HLA combination and ulcerative colitis and Crohn’s disease in a Japanese population

et al. 2018

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Inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn’s disease (CD). Natural killer cell responses play a crucial role in autoimmune disease through innate immunity, in which killer cell immunoglobulin-like receptors (KIRs) are closely involved. Although the genetic combination of KIRs with their specific HLA class I ligands has been associated with IBD in Caucasians, such KIR-HLA receptor-ligand combinations are not fully understood in the Japanese. We investigated 14 KIR genes along with HLA-Bw and -C ligands in 90 patients with UC and 50 patients with CD and compared them with the characteristics of 325 healthy control subjects. The frequency of HLA-Bw4 was significantly increased in patients with UC (P = 1.3 × 10−6; odds ratio [OR] = 3.39) and CD (P = 0.0065; OR = 2.32) versus controls. The UC group had a significantly higher frequency of KIR2DS3 (P = 0.024; OR = 1.94) and lower frequency of KIR2DS4 (P = 0.019; OR = 0.40) and KIR2DL1-HLA-C2 (P = 0.035; OR = 0.47). The Tel-A/B haplotype was significantly decreased in UC patients (P = 0.0056; OR = 0.49). The frequency of KIR3DL1-HLA-Bw4 was significantly higher in patients with UC (P = 4.3 × 10−6; OR = 3.12) and CD (P = 0.0067; OR = 2.30). In conclusion, HLA-Bw4 and KIR-HLA pairs may play an important role in the genetic susceptibility to IBD in the Japanese.

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“…The eQTL analysis showed that one of the SNPs, rs11672983, was associated with the expression of genes within the KIR gene complex. In line with this finding, Lopez-Hernandez et al [48] identified KIR2DS1 and KIR2DS5 as significant risk factors in Spanish IBD patients. Taken together, the studies suggest that imbalances between activating and inhibitory KIR genes and their ligands may explain, at least in part, the pathogenesis of the inflammatory bowel diseases.…”

Section: Discussionmentioning

confidence: 57%

Activating Killer-cell Immunoglobulin-like Receptor genes confer risk for Crohn’s disease in children and adults of the Western European descent: Findings based on case-control studies

et al. 2019

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Background Killer-cell Immunoglobulin-like Receptor (KIR) genes encode receptors, which are mainly expressed on, and control functional activities of, Natural Killer (NK) cells. There exist six distinct activating KIR genes in humans, who differ from one another with respect to the repertoire of these genes. Because activated NK cells can potentially cause tissue destruction, we hypothesized that variation in the inherited activating KIR genes in humans is associated with their innate susceptibility/resistance to developing Crohn disease (CD). Methods We performed case control studies on three independent Canadian CD patient cohorts (all of the Western European descent): two comprising children (Montreal having 193 cases and 245 controls, and Ottawa having 93 cases and 120 controls) and the third one comprising predominantly adults (Winnipeg having 164 cases and 200 controls). We genotyped cases and controls for activating KIR genes by PCR with gene-specific primers and investigated associations between the genes and cases using unconditional logistic regression. Results We observed strong associations between all the six KIR genes and CD in Ottawa children, with the strongest risk observed for the KIR2DS1 (p = 1.7 x10 -10 ). Associations between all but the KIR2DS2 were replicated in the Montreal cohort with the strongest association evident for the KIR2DS5 (8.0 x 10 −10 ). Similarly associations between five genes were observed in the adult Winnipeg cohort. In this cohort, strongest associations were evident with the KIR2DS5 (8.75 x 10 −8 ). An overall analysis for all cohorts showed strong associations with four of the genes, with the strongest association evident for the KIR2DS5 (p = 1.35 x 10− 17 ). In the combined analysis for four KIR genes, individuals carrying one or more of the KIR genes were at significantly higher risks for acquiring CD (p = 3.5 x 10 −34 ). Conclusions Activating KIR genes are associated with risk for developing CD in both children and adults.

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Killer immunoglobulin‐like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease

Cited by 10 publications

References 26 publications

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

Association between KIR-HLA combination and ulcerative colitis and Crohn’s disease in a Japanese population

Activating Killer-cell Immunoglobulin-like Receptor genes confer risk for Crohn’s disease in children and adults of the Western European descent: Findings based on case-control studies

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