Systemic sclerosis is a rare systemic autoimmune rheumatic disease which is thought to be polygenic disorder contributed by both genetic and environmental factors. A positive family history of SSc is the strongest risk factor yet identified for SSc; however, the absolute risk for each family member remains quite low. A systematic literature search was performed in MEDLINE and Scopus database for studies published only in English that investigated the prevalence of SSc in first-degree relatives of SSc patients and whether SSc family members have greater frequency of I autoantibodies (ATA) than expected. Following keywords and terms: "systemic sclerosis", "scleroderma", "familial","ATA", "topoisomerase", and "anti-Scl70" were used to select the appropriate articles. From the 21 initially identified articles, 16 were eliminated because of the inclusion criteria, and five articles concerning familial occurrence of SSc in first-degree relatives positive for ATA were included for further analysis. Two case reports were described-a daughter and a mother diagnosed with systemic sclerosis with ATA tested for specific genotype. In both cases, patients had antinuclear autoantibodies (ANA) at a titer of > 1:1280, AC-29 cell pattern according to ICAP, and their sera were positive for ATA. In addition, anti-SSA/Ro60 autoantibodies were found in the case of the mother. Complementary to ATA positivity, the daughter was also positive for AMA-M2 autoantibodies. The results showed that our patients shared HLA-DRB1*1104-DQA1*0501-DQB1*0301 haplotype and had positive ATA, which corresponds to the strong association between ATA in white subjects and HLA-DRB1*1104, DQA1*0501, DQB1*0301 haplotype (OR = 6.93). Our patients not only shared a risky HLA haplotype for SSc but also manifested with a similar immunological activity, given that they were both positive for ATA. Although infrequent, ATA-positive SSc patients could develop scleroderma renal crisis, as in the case of the mother. Therefore, careful monitoring of the renal function is the best strategy for the case of the daughter. A positive family history is an important hint for patients suspected of autoimmune disease. The cases of familial SSc are quite rare, but they give us the opportunity to compare the genetic background, environmental risk factors, SSc phenotype, ANA type, and prevention of the complications in the course of the disease.

中文翻译：

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母亲和女儿患有系统性硬化症，具有易感 HLA 单倍型和抗拓扑异构酶 I 自身抗体。

系统性硬化症是一种罕见的系统性自身免疫性风湿性疾病，被认为是由遗传和环境因素共同作用的多基因性疾病。SSc 阳性家族史是迄今为止已确定的 SSc 最强危险因素；然而，每个家庭成员的绝对风险仍然相当低。在 MEDLINE 和 Scopus 数据库中对仅以英文发表的研究进行了系统文献检索，这些研究调查了 SSc 患者一级亲属中 SSc 的患病率，以及 SSc 家庭成员 I 自身抗体 (ATA) 的出现频率是否高于预期。使用以下关键词和术语：“系统性硬化症”、“硬皮病”、“家族性”、“ATA”、“拓扑异构酶”和“抗Scl70”来选择合适的文章。在最初确定的 21 篇文章中，有 16 篇因纳入标准而被排除，另外 5 篇涉及 ATA 阳性一级亲属中家族性 SSc 发生的文章被纳入进一步分析。描述了两个病例报告——一名女儿和一名母亲被诊断患有系统性硬化症，并进行了 ATA 特定基因型检测。在这两种情况下，患者的抗核自身抗体 (ANA) 滴度 > 1:1280，根据 ICAP 的 AC-29 细胞模式，并且他们的血清 ATA 呈阳性。此外，在母亲的病例中还发现了抗SSA/Ro60自身抗体。作为 ATA 阳性的补充，女儿的 AMA-M2 自身抗体也呈阳性。结果显示，我们的患者具有 HLA-DRB1*1104-DQA1*0501-DQB1*0301 单倍型，并且具有阳性 ATA，这对应于白人受试者中的 ATA 与 HLA-DRB1*1104、DQA1*0501、DQB1* 之间的强相关性0301 单倍型（OR = 6.93）。我们的患者不仅具有 SSc 的危险 HLA 单倍型，而且还表现出相似的免疫活性，因为他们都是 ATA 阳性。尽管罕见，但 ATA 阳性 SSc 患者可能会出现硬皮病肾危象，就像母亲的情况一样。因此，针对女儿的情况，仔细监测肾功能是最好的策略。阳性家族史对于疑似自身免疫性疾病的患者来说是一个重要提示。家族性 SSc 病例相当罕见，但它们使我们有机会比较遗传背景、环境危险因素、SSc 表型、ANA 类型以及病程中并发症的预防。