Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis
Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis
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DOI：
10.1186/1471-2474-15-67
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发表时间：
2014-03-06
影响因子：
2.3
通讯作者：
Burbelo, Peter D.
中科院分区：
文献类型：
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作者：
Gan, Lu;O'Hanlon, Terrance P.;Burbelo, Peter D.
背景：对与自身免疫条件不一致的双胞胎的研究为探索复杂的基因-环境相互作用引发的致病因素提供了一个独特的机会。方法：在这项横断面研究中，31对与肌炎或系统性红斑狼疮(SLE)不一致的单合子或双合子双胞胎以及匹配的健康对照对21种自身抗原的抗体进行了评估。结果：自身抗体图谱显示，42%的受影响双胞胎对自身抗原有显著的血清阳性反应。在许多受影响的双胞胎中，检测到针对两种或更多在系统性自身免疫性疾病中常见的自身抗原的高水平自身抗体，包括Ro52、Ro60、RNP-70K和/或RNP-A。相比之下，只有10%(3/31)的未感染双胞胎显示出血清阳性，这些免疫反应是针对系统性自身免疫性疾病中未见的单一自身抗原。虽然患病双胞胎和非患病双胞胎之间对甲状腺过氧化物酶、转谷氨酰胺酶和几种细胞因子的自身抗体没有显著差异，但患有肌炎的双胞胎中有23%的人表现出对胃ATPase的自身抗体。对同卵双胞胎的分析还显示，与未感染的双胞胎相比，患病双胞胎的自身抗体频率更高(P=0.046)。最后，对同卵和异卵双生子的临床分析显示，自身抗体阳性的双生子的疾病活动性评分高于血清阴性的双生子(P=0.019)。结论：肌炎和系统性红斑狼疮的双生子的自身抗体显著高于未感染的双胞胎，这与在自身抗体产生和自身免疫性疾病的发病机制中发挥作用的潜在非遗传因素一致。
Background: Studies of twin pairs discordant for autoimmune conditions provide a unique opportunity to explore contributing factors triggered by complex gene-environment interactions.Methods: In this cross-sectional study, thirty-one monozygotic or dizygotic twin pairs discordant for myositis or systemic lupus erythematosus (SLE), along with matched healthy controls were evaluated for antibodies against a panel of 21 autoantigens.Results: Autoantibody profiling revealed that 42% of the affected twins showed significant seropositivity against autoantigens in the panel. In many of these affected twins, but none of healthy controls, there were high levels of autoantibodies detected against two or more autoantigens commonly seen in systemic autoimmune diseases including Ro52, Ro60, RNP-70 K and/or RNP-A. In contrast, only 10% (3/31) of the unaffected twins showed seropositivity and these immunoreactivities were against single autoantigens not seen in systemic autoimmune diseases. While no significant differences in autoantibodies were detected between the affected or unaffected twins against thyroid peroxidase, transglutaminase and several cytokines, 23% of the affected twins with myositis showed autoantibodies against the gastric ATPase. Analysis of the monozygotic twins separately also revealed a higher frequencies of autoantibodies in the affected twins compared to the unaffected twins (P = 0.046). Lastly, clinical analysis of both the affected monozygotic and dizygotic twins revealed that the autoantibody seropositive affected twins had a greater global disease activity score compared to seronegative affected twins (P = 0.019).Conclusion: The findings of significantly more autoantibodies in the affected twins with myositis and SLE compared to the unaffected twins are consistent with potential non-genetic factors playing a role in autoantibody production and pathogenesis of these autoimmune disorders.