Anti-CD146 Autoantibodies: The First Biologic Markers Associated With Occupational Exposure in Systemic Sclerosis

Systemic sclerosis (SSc) is a severe autoimmune disease, with occupational exposure being a significant risk factor. Because CD146 was recently identified as a driver of fibrosis in SSc through regulation of the Wnt/reactive oxygen species interplay, we hypothesized that it is a major autoimmune target in this disease.

We developed an in-house ELISA test to detect anti-CD146 autoantibodies (AACD146), which was confirmed by immunoprecipitation and Western blotting. AACD146 positivity was assessed in the sera of patients with SSc compared with healthy controls. A validation cohort of workers exposed to asbestos or silica was evaluated and compared to patients with pulmonary cancer and healthy controls without any occupational exposure.

Detection of AACD146 was assessed by ELISA and confirmed with Western blot and an absorption test. In the first cohort, the prevalence of positive AACD146 was significantly higher in patients with SSc (n = 14 of 93; 15%) than in controls (n = 2 of 40; 5%). Interestingly, among patients with SSc, positive AACD146 were associated with male sex (P = 0.04) and occupational exposure to silica (P = 0.009), with a sensitivity of 57% and specificity of 88% for occupational exposure. Results were confirmed in a validation cohort, in which positive AACD146 were found in 57% (n = 13 of 23) of patients with professional exposure. The frequency of AACD146 was significantly higher compared to controls (P = 0.03) and to patients with a history of cancer (P = 0.02).

We demonstrated that AACD146 are detectable in patients with SSc and are linked to male workers with occupational dust exposure. AACD146 are the first biomarkers associated with occupational exposure in SSc, with potential implications for preventive medicine.