Anti-CD146 autoantibodies may be detected more frequently in patients with systemic sclerosis and could be associated with occupational exposure—the first biologic marker associated with occupational exposure in the disease.
In a retrospective monocentric cohort of 93 patients with systemic sclerosis diagnosed according to 2013 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria, 15% (n = 14/93) patients tested positive for anti-CD146 autoantibodies (AACD146) compared with 5% (n = 2/40) of healthy blood donors. Positivity was defined using an in-house enzyme-linked immunosorbent assay coated with recombinant soluble CD146, with a sample-to-control optical density ratio greater than 1. Specificity of detection was supported by absorption experiments demonstrating signal reduction in positive samples and by Western blot recognition of recombinant soluble CD146 at 100 kDa.
Among the patients with systemic sclerosis, anti-CD146 positivity was associated with male sex and with occupational exposure (8% overall exposure prevalence), primarily to crystalline silica. The antibody demonstrated 57% sensitivity and 88% specificity for occupational exposure in this cohort. The investigators found that 29% (n = 4/14) of the antibody-positive patients had silica exposure compared with 4% (n = 3/79) of the antibody-negative patients. Anti-CD146 wasn't associated with disease severity by modified Rodnan skin score, organ involvement, cancer history, or treatment exposure.
External validation included 23 male workers with occupational exposure to silica, asbestos, or both. AACD146 were detected in 57% (n = 13/23). None of 7 patients with pulmonary cancer without occupational exposure of the three unexposed healthy controls tested positive. Within the exposed cohort, antibody status didn't statistically differ by age, exposure duration, or exposure type; however, interstitial lung disease was numerically more frequent in antibody-positive workers (31% vs 0%).
The investigators noted that systemic sclerosis related to silica exposure has been described, but no biologic marker has previously been identified. The study’s retrospective design and limited control sample size restrict temporal inference and generalizability, and larger prospective studies are planned.
“In conclusion, this study highlights AACD146 as a promising tool for the diagnosis and management of [systemic sclerosis] in the context of occupational disease, offering new insight into its pathogenesis,” noted lead study author Julien Bermudez, of the Aix Marseille Univ, APHM, INSERM, INRAE, C2VN, Hôpital Nord, Department of Respiratory Medicine in France, and colleagues.
Funding was provided by the Agence Nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail through the MacFibOsis project (2018/1/149). Julien Bermudez also received grant support from the Groupe Francophone de Recherche sur la Sclérodermie.
Source: ACR Open Rheumatology