Capillaroscopy and Immunological Profile in Systemic Sclerosis.

Introduction: Data on the associations between capillaroscopic changes and diagnostic systemic-sclerosis (SSc)-related antibodies are scarce. Presence of such correlation would improve current knowledge about the disease's pathogenesis by revealing the mechanisms of microangiopathy. The microvascular pathology of SSc is a hallmark of the disease, and immunological abnormalities probably contribute to its development. Patients and methods: 19 patients with definite diagnosis of SSc were included in the current pilot study; 16 had limited and 3 had diffuse cutaneous involvement; their mean age was 51.56 ± 15.07 years. All patients exhibited symptoms of Raynaud's phenomenon of the fingers. A "scleroderma" type capillaroscopic pattern was classified according to the staging suggested by Cutolo et al. (2000): "early", "active" or "late" phase. In the presence of different degrees of capillaroscopic changes in different fingers, the most-advanced microvascular pathology was chosen for classification. In cases without capillaroscopic features of microangiopathy, the findings were categorized as normal or nonspecific (dilated, tortuous capillaries, and/or hemorrhages). Indirect immunofluorescence on HEp-2 cells was performed as the gold-standard screening method for the detection of antinuclear autoantibodies (ANA), and determination of the immunofluorescent staining pattern (anti-cell pattern) was in accordance with the International Consensus on ANA Patterns. Scleroderma-associated autoantibodies in the patients' serum were assessed using line immunoblot assay for detection of autoantibodies to 13 scleroderma-associated autoantigens: Scl-70, CENP A, CENP B, RP11/RNAP-III, RP155/RNAP-III, fibrillarin, NOR-90, Th/To, PM-Scl100, PM-Scl75, Ku, PDGFR, and Ro-52. Results: In 73.7% (n = 14) of the examined patients, "scleroderma" type capillaroscopic changes were found, and in 26.3% (n = 5), capillaroscopic features of microangiopathy were absent (nonspecific changes, n = 3; normal findings, n = 2). In SSc patients with positive anti-Scl-70 (n = 7) antibodies, significantly lower mean capillary density was observed along with a higher frequency of "active" and "late" phase capillaroscopic changes as compared to the anti-Scl-70-negative patients (p < 0.05). Anti-RNAP III−155 positive patients (n = 4) had significantly higher mean capillary density than anti-RNAP III−155 negative patients (n = 15). In three of the anti-RNAP III−155-positive cases, capillaroscopic features of microangiopathy were not detected, and in one case there was an "early" phase "scleroderma" pattern. Conclusion: In the current pilot study, the association between more advanced capillaroscopic changes and the presence of anti-Scl-70 autoantibodies was confirmed. As a novel observation, positive anti-RNAP III−155 antibodies were found in SSc patients with or without early microangiopathy. The question of associations between microvascular changes in SSc and other SSc-related autoantibodies requires further research.

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

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.