Association of killer cell immunoglobulin-like receptor genes with primary Sjögren’s syndrome among Chinese population

IF 2.2 4区医学 Q3 IMMUNOLOGY Human Immunology Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI:10.1016/j.humimm.2025.111262

Shumin Zhang , Jing Xu , Wenjing Yue , Ye Yuan , Anhao Zheng , Wenbin Chen , Hongsheng Sun

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Abstract

Background

Primary Sjögren’s syndrome (pSS) is a chronic and common autoimmune disorder which is caused by inflammatory infiltration of the exocrine glands salivary glands and lacrimal glands are the main sites of involvement. Killer cell immunoglobulin-like receptors (KIRs), are crucial for the development and function of natural killer (NK) cells. Moreover, the activity of NK cells is affected by the interaction of KIRs with HLA class I ligands. The pathogenesis of autoimmune diseases has been linked to some KIR genes. Further research on the relationship between KIR and these autoimmune diseases is of great significance for the diagnosis and treatment of these diseases. This study aimed to detect and analyze the connection between the polymorphism of the KIR and HLA-Cw genes and the pathogenesis of pSS.

Methods

We took 56 pSS patients as the study group and 32 healthy people as the control group. Blood samples were collected to perform a polymerase chain reaction with sequence specific primers (PCR-SSP). Then a comparative analysis of gene frequencies of 16 KIR genes and HLA-Cw in the two groups was performed.

Results

The genotype frequencies of both KIR2DS3 (P = 0.0027) and KIR3DS1 (P = 0.006) were significantly lower in patients with pSS compared to healthy individuals, indicating a negative correlation of these two activating KIR genes. There were more individuals who had more than three activating KIR genes in the control group than in the patient group (P = 0.004). And the KIR2DL1/HLA-C2 gene combination (P = 0.022) was significantly more in pSS group than in controls.

Conclusion

Our results may imply that via influencing the activity, development, capacitation, and functionality of NK cells, NKT cells, and part T cells, the decrease of activated KIR genes and the increase of the frequency of the inhibitory KIR and its specific ligand gene combination（KIR2DL1/HLA-C2) may contribute to the pathogenesis of pSS.

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杀伤细胞免疫球蛋白样受体基因与中国人群原发性Sjögren综合征的关系

原发性Sjögren综合征（pSS）是一种慢性和常见的自身免疫性疾病，由外分泌腺的炎症浸润引起，唾液腺和泪腺是主要的受累部位。杀伤细胞免疫球蛋白样受体（KIRs）对自然杀伤细胞（NK）的发育和功能至关重要。此外，NK细胞的活性受到KIRs与HLA I类配体相互作用的影响。自身免疫性疾病的发病机制与一些KIR基因有关。进一步研究KIR与这些自身免疫性疾病的关系，对这些疾病的诊断和治疗具有重要意义。本研究旨在检测和分析KIR和HLA-Cw基因多态性与pSS发病机制的关系。方法以56例pSS患者为研究组，32例健康人为对照组。采集血样，用序列特异性引物（PCR-SSP）进行聚合酶链反应。比较分析两组患者16个KIR基因及HLA-Cw基因频率。结果pSS患者KIR2DS3基因型频率（P = 0.0027）和KIR3DS1基因型频率（P = 0.006）显著低于健康人群，表明这两种激活的KIR基因呈负相关。对照组中有3个以上激活KIR基因的个体多于患者组（P = 0.004）。pSS组KIR2DL1/HLA-C2基因组合显著高于对照组（P = 0.022）。结论通过影响NK细胞、NKT细胞和部分T细胞的活性、发育、获能和功能，激活KIR基因的减少和抑制性KIR及其特异性配体基因KIR2DL1/HLA-C2的频率增加可能参与了pSS的发病机制。

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来源期刊

Human Immunology 医学-免疫学

CiteScore

5.40

自引率

7.40%

发文量

107

审稿时长

12 days

期刊介绍： The journal''s scope includes understanding the genetic and functional mechanisms that distinguish human individuals in their immune responses to allografts, pregnancy, infections or vaccines as well as the immune responses that lead to autoimmunity, allergy or drug hypersensitivity. It also includes examining the distribution of the genes controlling these responses in populations. Research areas include: Studies of the genetics, genomics, polymorphism, evolution, and population distribution of immune-related genes Studies of the expression, structure and function of the products of immune-related genes Immunogenetics of susceptibility to infectious and autoimmune disease, and allergy The role of the immune-related genes in hematopoietic stem cell, solid organ, and vascularized composite allograft transplant Histocompatibility studies including alloantibodies, epitope definition, and T cell alloreactivity Studies of immunologic tolerance and pregnancy T cell, B cell, NK and regulatory cell functions, particularly related to subjects within the journal''s scope Pharmacogenomics and vaccine development in the context of immune-related genes Human Immunology considers immune-related genes to include those encoding classical and non-classical HLA, KIR, MIC, minor histocompatibility antigens (mHAg), immunoglobulins, TCR, BCR, proteins involved in antigen processing and presentation, complement, Fc receptors, chemokines and cytokines. Other immune-related genes may be considered. Human Immunology is also interested in bioinformatics of immune-related genes and organizational topics impacting laboratory processes, organ allocation, clinical strategies, and registries related to autoimmunity and transplantation.