Autoimmunity, Cancer, and Immunogenetics Research Laboratory, LR18SP12, Habib Bourguiba University Hospital of Sfax, University of Sfax, Sfax, Tunisia.
Department of Immunology, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia.
Int J Immunogenet. 2023 Aug;50(4):194-205. doi: 10.1111/iji.12625. Epub 2023 Jun 20.
The inducible T-cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen-presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case-control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (-693 G/A) and rs10932029 (IVS1 + 173 T/C); using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss.20. Our results revealed a significant association between ICOS gene rs11889031 > CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p = .001, odds ratio [OR] = 2.18 IC [1.36-3.49]); codominant genetic model 2, (C/C vs. T/T) p = .007, OR = 15.29 IC [1.97-118.5]); dominant genetic model, (C/C vs. C/T + T/T) p = .0001, OR = 2.44 IC [1.53-3.9]). Besides, there was a marginal association between rs11889031 > TT genotype and T allele with a protective role from SLE (recessive genetic model, p = .016, OR = 0.08 IC [0.01-0.63] and p = 7.6904E - 05, OR = 0.43 IC = [0.28-0.66], respectively). Moreover, statistical analysis indicated that the rs11889031 > CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti-SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031 > CC genotype with SLE, in contrast to a protective effect of rs11889031 > TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker.
诱导型 T 细胞共刺激分子 (ICOS) 可能通过调节 T 细胞与抗原呈递细胞之间的相互作用在适应性免疫中发挥重要作用。该分子的破坏可导致自身免疫性疾病，特别是红斑狼疮 (SLE)。在这项研究中，我们旨在探讨 ICOS 基因多态性与 SLE 之间的可能关联，以及它们对疾病易感性和临床结果的影响。我们进行了一项病例对照研究，包括 151 例 SLE 患者和 291 例在性别和地理来源上相匹配的无关健康对照 (HC)，以对位于 ICOS 基因中的两个多态性进行基因分型：rs11889031(-693 G/A)和 rs10932029(IVS1+173 T/C)；使用聚合酶链反应 (PCR)-限制性片段长度多态性方法。通过直接测序验证了不同的基因型。通过定量聚合酶链反应 (PCR) 在 SLE 患者和 HC 的外周血单核细胞中评估 ICOS mRNA 的表达水平。使用 Shesis 和 spss.20 进行分析。我们的结果表明，ICOS 基因 rs11889031>CC 基因型与 SLE 疾病之间存在显著关联（共显性遗传模型 1，(C/C 与 C/T)，p=0.001，优势比 [OR]=2.18 IC [1.36-3.49]）；共显性遗传模型 2，(C/C 与 T/T)，p=0.007，OR=15.29 IC [1.97-118.5]）；显性遗传模型，(C/C 与 C/T+T/T)，p=0.0001，OR=2.44 IC [1.53-3.9]）。此外，rs11889031>TT 基因型与 T 等位基因之间存在 SLE 保护作用的边缘关联（隐性遗传模型，p=0.016，OR=0.08 IC [0.01-0.63]和 p=7.6904E-05，OR=0.43 IC [0.28-0.66]）。此外，统计分析表明，rs11889031>CC 基因型与 SLE 的临床和血清学表现相关，包括血压和抗 SSA 抗体的产生。然而，ICOS 基因 rs10932029 多态性与 SLE 的易感性无关。另一方面，我们没有注意到这两个选定的多态性对 ICOS mRNA 基因表达水平有任何影响。该研究表明，ICOS rs11889031 与 SLE 存在显著的易感性关联，而 rs11889031>TT 基因型在突尼斯患者中具有保护作用。我们的结果表明，ICOS rs11889031 可能是 SLE 的风险因素，并可作为遗传易感性生物标志物。
