Zaripova Lina, Baigenzhin Abay, Zarkumova Zhanar, Zhabakova Zhanna, Boltanova Alyona, Solomadin Maxim, Pak Alexey
Department of Internal Medicine, JSC National Scientific Medical Center, Astana Medical University, 42 Abylai Khan Ave., Astana 010009, Kazakhstan.
School of Residency, Department of Internal Medicine No. 2, NCJSC Astana Medical University, 49/A Beibitshilik St., Astana 010000, Kazakhstan.
Epidemiologia (Basel). 2025 Aug 6;6(3):41. doi: 10.3390/epidemiologia6030041.
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. A PubMed search over the past 10 years was performed with "SSc-ILD", "autoantibodies", "cytokines", and "genes". Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc ( = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients.
系统性硬化症（SSc）是一种自身免疫性结缔组织疾病，其特征为血管异常、免疫功能障碍和进行性纤维化。SSc最常见的表现之一是间质性肺疾病（ILD），其病程呈进行性发展，可导致显著的发病率和死亡率。通过对一组哈萨克族SSc-ILD患者进行系统评价和分析，以研究SSc-ILD中的自身抗体、细胞因子和基因标志物。在过去10年中，利用“SSc-ILD”“自身抗体”“细胞因子”和“基因”等关键词在PubMed上进行了检索。对30例SSc患者进行了肺部受累情况、EScSG评分和改良Rodnan皮肤评分评估。采用酶联免疫吸附测定法检测白细胞介素-6（IL-6），通过间接免疫荧光法检测人喉表皮样癌细胞（HEp-2）上的抗核因子，通过免疫印迹法检测特异性自身抗体。在Ion Proton平台上使用一个包含120个基因的扩增子测序板进行基因分析。文献综述共识别出361篇文章，其中26篇涉及自身抗体，20篇涉及基因变异，12篇涉及细胞因子谱。IL-6、转化生长因子-β（TGF-β）、IL-33和肿瘤坏死因子-α（TNF-α）水平升高与SSc相关。基于系统评价结果，我们为哈萨克族SSc患者（n = 30）创建了一个初步的免疫原性检测板并进行了如下分析。其中14例（46.7%）表现出ILD和/或肺动脉高压的迹象，经常检测到抗Scl-70、U1-核糖核蛋白（U1-snRNP）、SS-A等抗体以及含SAM结构域蛋白9L（SAMD9L）、REL、白介素-1受体相关激酶1（IRAK1）、淋巴细胞抗原96（LY96）、IL-6受体（IL6R）、整合素α2β（ITGA2B）、自身免疫调节因子（AIRE）、三磷酸核苷外切酶1（TREX1）和CD40基因的基因变异。目前的研究证实了哈萨克族SSc-ILD患者中存在多种自身抗体以及IRAK1、肿瘤坏死因子α诱导蛋白3（TNFAIP3）、SAMD9L、REL、IRAK1、LY96、IL6R、ITGA2B、AIRE、TREX1、CD40基因的变异。
