Scleroderma Autoantibodies Might Reveal More About Disease Profiles Than Current Classification

Specific autoantibodies may give rise to clear differences in disease features among Spanish patients with scleroderma, according to a report in the journal Clinical and Experimental Rheumatology.

These differences are similar to those reported in other populations, and suggest that analyses of specific autoantibodies may provide physicians with additional information for the classification of scleroderma into the limited or diffuse skin involvement types.

The study, “Influence of antibody profile in clinical features and prognosis in a cohort of Spanish patients with systemic sclerosis,” recruited 209 patients from a Spanish scleroderma registry called RESCLE (Registro de ESCLErodermia).

The research team from the Institut Clinic de Medicina i Dermatología at the University Hospital Clínic, Barcelona, in Spain included only patients who tested positive for one of three anti-nuclear antibodies — anti-centromere (ACA), anti-topoisomerase I (ATA), or anti-RNA polymerase III (ARA).

Such antibodies are found in the majority of patients with scleroderma.

The presence of these antibodies was mutually exclusive, allowing the team to study the specific impact of each antibody.

Their work was inspired by the insight — made by other researchers — that the current classification of scleroderma into limited and diffuse cutaneous disease is not adequately mirroring how the disease impacts internal organs.

Specific antibodies could instead be used to predict how the disease will develop, they argued.

To support this idea, researchers compared demographics, symptoms, and outcomes of patients with the three different autoantibodies.

The group was composed of 61% of patients with ACA; 22% who tested positive for ATA; and 17% with ARA.

Patients with ACA were more likely to have limited scleroderma, with only 31% diagnosed with diffuse disease. In contrast, limited disease was less common in patients with ATA and ARA — 54% of those with ATA and 62% of ARA-positive patients had diffuse disease.

In addition, patients with ACA were more likely to have sine scleroderma — a type of the disease that lacks skin symptoms. ACA patients also often had a delayed diagnosis compared to patients with the other antibodies.

The three antibody types were found to be linked to specific symptoms or features. People with ACA were more likely women and the antibodies appeared protective for diffuse scleroderma. People with ACA were also unlikely to have joint pain as their first symptom or to develop interstitial lung disease.

People testing positive for ATA were unlikely to have limited or sine scleroderma. They were instead more prone to develop interstitial lung disease, particularly a so-called interstitial reticular pattern of lung fibrosis.

Patients with ARA were more likely to have diffuse disease and to develop joint pain as their first symptom. They tended to have more digital ulcers and experience scleroderma renal crisis more often.

Importantly, this group also had the highest cancer rate and more often developed cancer about the time as their scleroderma diagnosis, although the differences were not significant. Similar findings in other studies, however, have prompted experts to suggest that all ARA-positive patients should be screened for cancer at diagnosis.

The team found no significant difference in mortality rates or in causes of death between the three groups.

Based on the results, researchers concluded that the symptom profiles linked to the three autoantibodies suggest that antibody-analyses may aid physicians in the management of scleroderma by providing better insights into the symptoms a patient is likely to experience.