Department of Immunology and Translational Research, Canberra Hospital, and Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
J Allergy Clin Immunol. 2013 Apr;131(4):1130-5, 1135.e1. doi: 10.1016/j.jaci.2012.06.023. Epub 2012 Jul 31.
The 1858T allele of protein tyrosine phosphatase nonreceptor type 22 (PTPN22; R620W) exhibits one of the strongest and most consistent associations with sporadic autoimmune disease. Although autoimmunity is common in patients with primary antibody deficiency (PAD), it remains unknown whether its pathogenesis is similar when it arises in this context compared with in immunocompetent patients.
We set out to determine whether the 1858T allele of PTPN22 was associated with PAD or with autoimmunity in the context of PAD.
We genotyped rs2476601 (g.1858C>T), a single nucleotide polymorphism encoding substitution of arginine for tryptophan in PTPN22 (R620W), in 193 patients with PAD and 148 control subjects from an Australian cohort. We also performed a subgroup analysis according to the presence of autoimmunity and B-cell phenotypes.
C/T and T/T PTPN22 genotypes were more common in patients with PAD than in the matched control subjects (C/T, 18.1% vs 9.5%; T/T, 1.04% vs 0.6%). The T allele was associated with an increased risk of PAD relative to control subjects (odds ratio, 2.10; 95% CI, 1.11-4.00). The distribution of genotypes in control subjects was similar to those reported previously and did not deviate significantly from Hardy-Weinberg equilibrium. We found a strong association between the 1858T allele and PAD with coexistent autoimmune diseases. In patients with PAD and autoimmunity, 16 (43.2%) of 37 had at least one T allele of PTPN22 compared with 27 (17.3%) of 156 with the C/C genotype (P=.0014; odds ratio, 3.64; 95% CI, 1.68-7.88). We found no evidence that this effect was mediated by enrichment of CD21low B cells.
The 1858T PTPN22 allele is strongly associated with autoimmunity in patients with PAD.
蛋白酪氨酸磷酸酶非受体型 22（PTPN22；R620W）的 1858T 等位基因与散发性自身免疫性疾病有着最强和最一致的关联之一。尽管原发性抗体缺陷（PAD）患者中常发生自身免疫，但尚不清楚其发病机制在这种情况下与免疫功能正常的患者相比是否相似。
我们旨在确定 PTPN22 的 1858T 等位基因是否与 PAD 患者中的 PAD 或自身免疫相关。
我们对来自澳大利亚队列的 193 例 PAD 患者和 148 例对照者的 rs2476601（g.1858C>T）进行基因分型，该单核苷酸多态性编码 PTPN22 中精氨酸取代为色氨酸（R620W）。我们还根据自身免疫和 B 细胞表型进行了亚组分析。
与匹配的对照组相比，PAD 患者中 C/T 和 T/T PTPN22 基因型更为常见（C/T，18.1%比 9.5%；T/T，1.04%比 0.6%）。与对照组相比，T 等位基因与 PAD 风险增加相关（比值比，2.10；95%CI，1.11-4.00）。对照组的基因型分布与先前报道的相似，且未明显偏离 Hardy-Weinberg 平衡。我们发现 1858T 等位基因与 PAD 伴自身免疫性疾病之间存在很强的关联。在 PAD 伴自身免疫的患者中，37 例中有 16 例（43.2%）至少有一个 PTPN22 的 T 等位基因，而在 156 例 C/C 基因型的患者中，有 27 例（17.3%）（P=.0014；比值比，3.64；95%CI，1.68-7.88）。我们没有发现证据表明这种效应是由 CD21low B 细胞的富集介导的。
1858T PTPN22 等位基因与 PAD 患者的自身免疫密切相关。
