Activating killer immunoglobulin-like receptors genes are associated with increased susceptibility to ankylosing spondylitis

Díaz‐Peña, Roberto; Vidal-Castiñeira, José Ramón; Mulero, Juan; Sánchez, Alejandra; Queiró, Rubén; López‐Larrea, Carlos

doi:10.1111/cei.12568

Cited by 19 publications

(11 citation statements)

References 31 publications

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“…Increased percentages of NK cells expressing activating KIRs may result from increased frequencies of these genes occurring in CD patients [18]. Increased frequencies of activating KIR genes and of inhibitory KIR genes, which encode receptors with lower affinities for their MHC class I ligands, have been associated with several human autoimmune and chronic inflammatory conditions that include sepsis, ankylosing spondylitis, systemic lupus erythematous, leukemia, type 1 diabetes, and autism [49][50][51][52][53][54], reviewed in [15,16]. In this regard, similar trends were observed in IBD patients by some researchers but not by others (reviewed in [55]).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

Samarani

Sagala

Jantchou

et al. 2020

Mediators of Inflammation

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We investigated activation status, cytotoxic potential, and gut homing ability of the peripheral blood Natural Killer (NK) cells in Crohn disease (CD) patients. For this purpose, we compared the expression of different activating and inhibitory receptors (KIR and non-KIR) and integrins on NK cells as well as their recent degranulation history between the patients and age-matched healthy controls. The study was conducted using freshly obtained peripheral blood samples from the study participants. Multiple color flow cytometry was used for these determinations. Our results show that NK cells from treatment-naïve CD patients expressed higher levels of activating KIR as well as other non-KIR activating receptors vis-à-vis healthy controls. They also showed increased frequencies of the cells expressing these receptors. The expression of several KIR and non-KIR inhibitory receptors tended to decrease compared with the cells from healthy donors. NK cells from the patients also expressed increased levels of different gut-homing integrin molecules and showed a history of increased recent degranulation events both constitutively and in response to their in vitro stimulation. Furthermore, treatment of the patients tended to reverse these NK cell changes. Our results demonstrate unequivocally, for the first time, that peripheral blood NK cells in treatment-naïve CD patients are more activated and are more poised to migrate to the gut compared to their counterpart cells from healthy individuals. Moreover, they show that treatment of the patients tends to normalize their NK cells. The results suggest that NK cells are very likely to play a role in the immunopathogenesis of Crohn disease.

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Section: Discussionmentioning

confidence: 99%

Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

Samarani

Sagala

Jantchou

et al. 2020

Mediators of Inflammation

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“…The initial search selected 470 potentially related studies. Based on the inclusion criteria, 12 articles with 1770 cases and 2907 healthy subjects were included in the final meta‐analysis . All the papers were case‐control studies and among them, 7 studies were conducted in Asia and 5 in Europe.…”

Section: Resultsmentioning

confidence: 99%

“…Based on the inclusion criteria, 12 articles with 1770 cases and 2907 healthy subjects were included in the final metaanalysis. 32,38,39,[41][42][43][44][49][50][51][52][53] All the papers were case-control stud-…”

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

“…This may be due to diverse study populations of different ethnicities, lack of statistical power, limited sample sizes, difficulty in defining the phenotype, and the level of linkage disequilibrium between genotypes . While Mahmoudi et al, Díaz‐Peña et al and Su‐Jin et al reported that imbalance of KIR genes might be a genetically contributing factor in susceptibility to AS, the other studies in British, Chinese, Spanish, Portuguese, Russian, Iranian, as well as Thais failed to find such an association …”

Section: Introductionmentioning

confidence: 99%

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Association study between killer immunoglobulin‐like receptor polymorphisms and ankylosing spondylitis disease: An updated meta‐analysis

et al. 2018

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Background Several genetic studies have assessed the association between polymorphisms in killer immunoglobulin‐like receptors (KIR) genes and susceptibility of individuals to ankylosing spondylitis (AS), but the findings have been inconclusive and incongruous. Therefore, we conducted this meta‐analysis of all case‐control studies meeting the inclusion criteria for obtaining an exact conclusion of the effect of KIR polymorphisms on the risk of AS. Methods A systematic literature search was conducted in electronic databases, including Scopus web of science, ScienceDirect, and PubMed to find all eligible studies exploring the association between KIR polymorphisms and the risk of AS, prior to June 2017. Pooled odds ratios (OR) and their corresponding 95% CIs were used to evaluate the strength of the association between KIR polymorphisms and the risk of AS. Results A total of 16 case‐control studies, encompassed in 12 papers, with 1770 cases and 2907 healthy subjects were included in the meta‐analysis. This meta‐analysis revealed three significant positive associations of 2DS1, 2DS5, and 3DS1 with susceptibility to AS, while two significant negative associations of 2DL2 and 2DS2 with susceptibility to AS were identified. In the subgroup analysis based on human leukocyte antigen (HLA)‐B*27 positive patients and healthy subjects, results indicated that there were four significant positive associations between 2DL5, 2DS4, 2DS5, 3DS1 polymorphisms and susceptibility to AS in HLA‐B*27‐positive patients; a significant negative association of 3DL1 in HLA‐B*27‐positive patients was found. Conclusions While 2DS1, 2DS5, and 3DS1 polymorphisms increased AS risk, 2DL2 and 2DS2 polymorphisms were associated with reduced AS susceptibility.

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“…Several studies have investigated the association between KIR/HLA genotypes and autoimmune disease, infectious disease, transplantation, stem cell disease and malignancy (15)(16)(17). Regarding malignant diseases, certain KIR/HLA types have been associated with the susceptibility or worse clinical outcome in several types of cancer, such as leukemia, colorectal cancer and lung cancer (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Typing of killer-cell immunoglobulin-like receptors and their cognate human leukocyte antigen class I ligands predicts survival of Chinese Han patients with metastatic non-small-cell lung cancer

Liu

Sansas

et al. 2016

Molecular and Clinical Oncology

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Abstract. Non-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth. Natural killer (NK) cells play a pivotal role in immunological surveillance. Activation of NK cells partially depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. We herein investigated the association of KIRs and HLA ligands with survival in metastatic NSCLC (mNSCLC) patients treated with chemotherapy in a Chinese Han population. Polymerase chain reaction with sequence-specific primers was used to type 15 KIRs at the DNA and mRNA level and 6 HLA ligands in 70 mNSCLC patients. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression model was applied for multivariate survival analysis, with the stepwise selection, to determine independent predictors of survival. It was observed that patients with KIR2DS4del gene expression at the mRNA level or HLA-Bw4T80 exhibited poor overall survival (OS). The multivariate analysis revealed that HLA-Bw4T80 and KIR2DS4del expression were independent predictors of OS. This observation indicated that the KIR/HLA ligand is a promising predictor of survival in mNSCLC and may also provide a strategy for treatment stratification and patient management. IntroductionNon-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth (1). Natural killer (NK) cells play a pivotal role in innate immunity and immunological surveillance (2). Activation of NK cells partly depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands (3). KIRs are a family of cell surface receptors expressed by NK cells and certain subpopulations of T lymphocytes. The KIR family consists of inhibitory as well as activating receptors characterized by both allelic (high numbers of variants) and haplotypic (different numbers of genes for inhibitory and activating receptors on individual chromosomes) polymorphisms (4). The ligands of KIRs are specific epitopes on HLA class I molecules (5). HLA-C allotypes fall into the C1 or C2 groups (asparagine and lysine, respectively, at position 80) that are recognized by KIR2DL2/KIR2DL3 and KIR2DL1/KIR2DS1, respectively. Two previous studies have implicated HLA-C1 and HLA-C2 as potential ligands for KIR2DS4 (6,7). KIR3DL1/KIR3DS1 recognizes HLA-Bw4 epitopes of HLA-A and HLA-B alleles, which are classified according to whether isoleucine or threonine is present at position 80 (4).An increased understanding of the complexities of the biology of the KIR/HLA system has provided opportunities to leverage NK cell function as a novel avenue of immunotherapy for cancer (8 HLA, human leukocyte antigen; NK, natural killer; NSCLC, non-small-cell lung cancer; mNSCLC, metastatic non-small-cell lung cancer; SSP-PCR, sequence-specific primer polymerase chain reaction;...

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Activating killer immunoglobulin-like receptors genes are associated with increased susceptibility to ankylosing spondylitis

Cited by 19 publications

References 31 publications

Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

Association study between killer immunoglobulin‐like receptor polymorphisms and ankylosing spondylitis disease: An updated meta‐analysis

Typing of killer-cell immunoglobulin-like receptors and their cognate human leukocyte antigen class I ligands predicts survival of Chinese Han patients with metastatic non-small-cell lung cancer

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