Autoantibodies tied to symptoms, complications in scleroderma study
Findings suggest limited value of broad antibody testing without overlap
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Specific self-reactive antibodies are associated with different symptoms and complications in people with systemic sclerosis (SSc) without overlap syndrome, a study in Brazil shows.
For instance, autoantibodies targeting Scl70 or centromere were tied to differences in when the disease starts, how the skin is affected, and the risk of lung complications, supporting their value for SSc diagnosis and prognosis. Overlap syndrome occurs when SSc patients have features of other autoimmune diseases alongside SSc.
Although autoantibodies not specific to SSc were frequently detected in these patients, they showed few links to disease complications, raising questions about “the routine utility of broad, untargeted antibody testing in this specific population,” the researchers wrote.
The study, “Clinical Relevance of Specific and Non-Specific Autoantibodies in Systemic Sclerosis Without Overlap Features,” was published in Seminars in Arthritis and Rheumatism.
Autoantibodies play key role in scleroderma diagnosis, care
In SSc, self-reactive antibodies, or autoantibodies, target the body’s connective tissues, contributing to excess collagen buildup and scarring in the skin and internal organs. Blood tests to detect autoantibodies — particularly antinuclear antibodies, which target proteins in the cell nucleus — can help support diagnosis of SSc.
However, “the prevalence and clinical significance of non-SSc-specific autoantibodies, including those observed in other immune-mediated inflammatory diseases (IMIDs), remain incompletely understood in the context of SSc patients without associated overlap syndrome,” the researchers wrote.
To learn more, researchers in Brazil analyzed 263 SSc patients followed at the University of São Paulo. Participants had a mean age at disease onset of 42.4 years and were mainly women (89.7%) and White (77.2%). Regarding SSc type, more than half had limited SSc (53.6%), 35% had diffuse SSc, and 11.4% had SSc sine sclerosis.
The most frequent skin symptoms included digital ulcers (66.9%), or sores in the fingers and toes, and telangiectasias (62.7%) — widened blood vessels visible near the skin surface. Calcinosis, or calcium deposits, was present in about 20% of patients. The most frequently affected internal organs were the esophagus (90.9%) and the lungs (72.3%).
Most participants (88.2%) tested positive for antinuclear antibodies, while 82.9% had SSc-specific antibodies, including anti-Scl70 (31.5%), anti-centromere (27%), and anti-RNA polymerase III (8%). Having these antibodies was largely mutually exclusive, meaning patients tended to have only one of them. Non-SSc-specific antibodies included anti-Ro52 (36.1%), anti-rheumatoid factor (18.5%), and anti-ribonucleoprotein (10.5%).
Non-specific antibodies show limited clinical relevance
Additionally, the most frequently identified IMID-specific antibodies were anti-cyclic citrullinated peptide (5.3%) and anti-Smith (1.9%). The researchers noted that broader testing for other IMID-specific antibodies, which were not consistently confirmed with more specific testing, had limited clinical utility in SSc patients without overlap features.
The team then found that SSc-specific antibodies were associated with several clinical manifestations. For instance, anti-Scl70 antibodies were associated with earlier disease onset, diffuse SSc, digital ulcers, interstitial lung disease (ILD) — where the lungs become scarred — and a lower frequency of pulmonary hypertension (high blood pressure in the blood vessels that supply the lungs).
The presence of anti-centromere antibodies was linked to later disease onset, limited SSc, telangiectasias, Barrett’s esophagus (a condition affecting the esophagus), and a lower frequency of ILD. Also, having anti-RNA polymerase antibodies was associated with diffuse SSc and esophageal involvement.
Regarding non-specific antibodies, the only statistically significant association was between anti-ribonucleoprotein antibodies and a higher frequency of ILD, although this was not linked to more severe lung disease.
There were also inverse relationships between some antibodies, meaning certain types were less likely to occur together. This may help with disease diagnosis and prediction of disease progression, “supporting more personalized monitoring strategies in daily practice,” the researchers wrote.
Overall, “these results underscore the importance of judicious interpretation of autoantibody profiles and support a more selective approach to isolated [antibody] testing,” they added.
