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Systemic sclerosis in mother and daughter with susceptible HLA haplotype and anti-topoisomerase I autoantibodies

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Abstract

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.

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Authors and Affiliations

  1. Laboratory of Clinical Immunology, Department of Clinical Immunology, University Hospital “St. Ivan Rilski”, Medical University of Sofia, Ivan Geshov Str. 15, 1431, Sofia, Bulgaria

    Ekaterina Krasimirova Kurteva

  2. Department of Internal Medicine, Clinic of Rheumatology, University Hospital “St. Ivan Rilski”, Medical University of Sofia, 13 Urvich Str., 1612, Sofia, Bulgaria

    Vladimira Vasileva Boyadzhieva & Nikolay Rumenov Stoilov

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  1. Ekaterina Krasimirova Kurteva
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Correspondence to Vladimira Vasileva Boyadzhieva.

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Kurteva, E.K., Boyadzhieva, V.V. & Stoilov, N.R. Systemic sclerosis in mother and daughter with susceptible HLA haplotype and anti-topoisomerase I autoantibodies. Rheumatol Int 40, 1001–1009 (2020). https://doi.org/10.1007/s00296-020-04516-5

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