Pediatric Nephrology Unit, Mansoura University Children's Hospital, Faculty of Medicine, Mansoura University, Egypt.
Immunology unit, clinical pathology department, Faculty of medicine, Mansoura university, Egypt; Immunology department, Egypt center for research and regenerative medicine, Cairo, Egypt.
Lupus. 2021 Aug;30(9):1449-1458. doi: 10.1177/09612033211020359. Epub 2021 Jun 3.
Many genes have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF) is a potent cytokine stimulator acting through 2 cell surface receptors (TNFR I and II). TNFRII gene which controls expression of these receptors has been linked to SLE susceptibility through promoting apoptosis. Also; Protein tyrosine phosphatase non receptor 22 (PTPN22) gene enhances intrinsic phosphatase activity of T lymphocytes leading to their dysregulation and stimulates autoimmune process of lupus and its rs2476601 has been linked to susceptibility to thyroiditis in SLE patients in few studies.
(i) to investigate the correlation between 2 SNPs of TNFR II and PTPN22 genes and SLE susceptibility in a cohort of Egyptian children compared to controls (ii) and to investigate their possible association with different clinical presentations of the disease in children.
Typing of TNFR II rs1061622 and PTPN22 rs2476601 SNPs were done using polymerase chain reaction-restriction fragment length polymorphism for 74 children with SLE and 100 matched healthy controls.
Children with SLE had more frequent G allele and GG genotype of TNFR II rs1061622 ( < 0.001) and more T allele and TT genotype of PTPN22 rs2476601 ( = 0.012 and <0.001, respectively) compared to controls. Only 6 patients (8%) had thyroiditis (hypothyroidism) with T allele and TT genotype of PTPN22 1858 T more prevalent in those patients versus those without thyroiditis ( ≤ 0.001). Apart from, thyroiditis, no significant association was found between genotypes and alleles frequencies of the 2 studied SNPs and other clinical manifestations of the disease.
The G allele and GG genotype of TNFR II rs1061622 and T allele and TT genotype of PTPN22 rs2476601 genes polymorphism can be considered as risk factors for the development of SLE. The presence of the T allele of PTPN22 rs2476601 may increase the risk of concomitant thyroiditis in Egyptian children with SLE but further studies are required to confirm this finding as thyroiditis was reported only in few cases in this study.
许多基因与系统性红斑狼疮（SLE）的发病机制有关。肿瘤坏死因子（TNF）是一种有效的细胞因子刺激物，通过 2 种细胞表面受体（TNFR I 和 II）发挥作用。控制这些受体表达的 TNFRII 基因通过促进细胞凋亡与 SLE 易感性有关。此外；蛋白酪氨酸磷酸酶非受体 22（PTPN22）基因增强 T 淋巴细胞的固有磷酸酶活性，导致其失调，并刺激狼疮的自身免疫过程，其 rs2476601 已在一些研究中与 SLE 患者的甲状腺炎易感性有关。
（i）在埃及儿童队列中研究 TNFR II 和 PTPN22 基因的 2 个 SNP 与 SLE 易感性的相关性，并与对照组进行比较；（ii）并研究它们与儿童疾病不同临床表现的可能关联。
采用聚合酶链反应-限制性片段长度多态性对 74 例 SLE 患儿和 100 例匹配的健康对照者进行 TNFR II rs1061622 和 PTPN22 rs2476601SNP 分型。
与对照组相比，SLE 患儿 TNFR II rs1061622 的 G 等位基因和 GG 基因型（<0.001）以及 PTPN22 rs2476601 的 T 等位基因和 TT 基因型（=0.012 和 <0.001）更为频繁。只有 6 例（8%）患者存在甲状腺炎（甲状腺功能减退），PTPN22 1858T 的 T 等位基因和 TT 基因型在这些患者中更为常见（<0.001）。此外，除了甲状腺炎之外，在这两个研究 SNP 的基因型和等位基因频率与疾病的其他临床表现之间没有发现显著的相关性。
TNFR II rs1061622 的 G 等位基因和 GG 基因型以及 PTPN22 rs2476601 的 T 等位基因和 TT 基因型可视为 SLE 发生的危险因素。PTPN22 rs2476601 的 T 等位基因的存在可能会增加埃及 SLE 儿童同时发生甲状腺炎的风险，但需要进一步研究来证实这一发现，因为在本研究中仅报告了少数甲状腺炎病例。
