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伊朗重症肌无力患者杀伤细胞免疫球蛋白样受体(KIR)及其 HLA 配体的研究。

The investigation of killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands in Iranian patients with myasthenia gravis.

机构信息

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Clin Neurol Neurosurg. 2024 Mar;238:108171. doi: 10.1016/j.clineuro.2024.108171. Epub 2024 Feb 13.

Abstract

BACKGROUND

Myasthenia gravis (MG) is a disabling disease with the underlying pathophysiology of auto-antibodies attacking the postsynaptic acetylcholine receptors of neuromuscular junctions causing muscle weakness. Natural killer (NK) cells are innate immune cells that play an important regulative role in immune responses. The human killer-cell immunoglobulin-like receptors (KIRs) family is one of the receptors on NK cells that can either activate or inhibit NK cells. This study aimed to assess the possible role of KIR and their human leukocyte antigen (HLA) ligand genes susceptibility to MG in Iranian patients.

METHOD

One hundred and sixty-three patients with MG diagnosis based on the presence of clinical symptoms and laboratory tests and 400 healthy volunteers were studied. We used the polymerase chain reaction (PCR) technique for genotyping 15 KIRs and 5 HLA genes.

RESULTS

The results demonstrated that there was no significant difference in the frequency of KIR genes and inhibitory KIR genotypes between controls and patients. In MG patients, HLA-C1 was significantly less frequent than in matched controls. The frequency of HLA genotype number 7 was significantly lower in MG cases, compared to the controls. Analysis of activating KIR genotypes showed that genotype number 10 was significantly less frequent in MG cases than in matched controls.

CONCLUSION

Our results suggest that the presence HLA-C1 might play a protective role against the pathogenesis of MG. The significantly decreased prevalence of one activating KIR genotype and one of the HLA genotypes in MG cases suggest that these genotypes can reduce the risk of MG development. To specifically reveal the impact of KIR and HLA in MG, more studies are required.

摘要

背景

重症肌无力(MG)是一种使人丧失能力的疾病,其潜在的病理生理学是自身抗体攻击神经肌肉接头的突触后乙酰胆碱受体,导致肌肉无力。自然杀伤(NK)细胞是先天免疫细胞,在免疫反应中发挥着重要的调节作用。人类杀伤细胞免疫球蛋白样受体(KIR)家族是 NK 细胞上的一种受体,它可以激活或抑制 NK 细胞。本研究旨在评估 KIR 及其人类白细胞抗原(HLA)配体基因对伊朗 MG 患者易感性的可能作用。

方法

本研究共纳入 163 名 MG 患者(基于临床症状和实验室检查诊断)和 400 名健康志愿者。我们使用聚合酶链反应(PCR)技术对 15 种 KIR 基因和 5 种 HLA 基因进行基因分型。

结果

结果表明,对照组和患者组之间 KIR 基因和抑制性 KIR 基因型的频率没有显著差异。在 MG 患者中,HLA-C1 明显较对照组少见。与对照组相比,MG 病例中 HLA 基因型数 7 的频率显著降低。分析激活型 KIR 基因型显示,MG 病例中基因型数 10 的频率明显低于对照组。

结论

我们的结果表明,HLA-C1 的存在可能对 MG 的发病机制起到保护作用。MG 病例中一种激活型 KIR 基因型和一种 HLA 基因型的显著减少提示这些基因型可以降低 MG 发病的风险。为了更具体地揭示 KIR 和 HLA 在 MG 中的作用,还需要更多的研究。

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