Anti-CD146 antibodies may signal occupational exposure in SSc: Study
It's first biomarker linked to silica and other environmental triggers
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Measuring the blood levels of anti-CD146 antibodies may help identify people with systemic sclerosis (SSc) whose disease is associated with occupational exposure to silica and other mineral dusts, according to a small study.
This is the first biomarker linked to occupational exposure identified in SSc. Detecting these antibodies could help doctors identify patients whose disease may be driven by specific environmental triggers and guide monitoring strategies to detect other occupational diseases linked to those exposures early.
The study, “Anti-CD146 Autoantibodies: The First Biologic Markers Associated With Occupational Exposure in Systemic Sclerosis,” was published in the journal ACR Open Rheumatology.
Genetic, environmental factors thought to contribute to SSC
SSc is an autoimmune disease marked by progressive tissue scarring, or fibrosis, in the skin and internal organs. Both genetic and environmental factors are thought to contribute to its development, and exposure to substances such as silica or certain solvents has been linked to an increased risk of the disease.
Recent research suggests that CD146 may drive fibrosis in SSc, and that lower blood levels of its soluble form are associated with disease progression.
Exposure to silica is known to trigger oxidative stress — a form of cellular damage caused by reactive oxygen species — which can alter CD146 production. These changes may make the protein appear abnormal to the immune system, potentially triggering the production of self-reactive antibodies against CD146.
To examine this possibility, researchers in France investigated whether people with SSc develop autoantibodies targeting CD146 and whether their presence is associated with occupational exposure to silica and other mineral dusts.
29% of antibody-positive patients had history of silica exposure
The team analyzed blood samples from 93 people with SSc followed at a hospital in Marseille and 40 healthy blood donors. Most patients were women (89%) and the average age at diagnosis was 50. About two-thirds of patients had the cutaneous form of SSc, which mostly affects the skin, while about one-third had systemic disease, which also causes damage to internal organs.
Results showed that 15% of SSc patients tested positive for anti-CD146 autoantibodies, compared with 5% of healthy controls.
Among SSc patients, these antibodies were more common in men and were significantly associated with occupational exposure to silica and other mineral dusts. Notably, 29% of antibody-positive patients had a history of silica exposure, while 4% of those who tested negative had been exposed to either silica or aluminum.
“We identified [anti-CD146 antibodies] as the first biologic marker for SSc linked to occupational exposure, marking the first identification of an autoimmune response against CD146,” the researchers wrote.
To validate that link, the team looked at a second group of 23 workers exposed to mineral dusts, including silica and asbestos. In that group, 57% (13 of 23) tested positive for anti-CD146 antibodies, while none of the healthy donors (0%) were positive for those antibodies.
Workers testing positive for these antibodies might benefit from enhanced monitoring to detect potential occupational diseases early or to promptly cease exposure.
The team also examined a group of people with lung cancer who had no occupational exposure, as cancer can lead to the production of autoantibodies. None of these individuals had antibodies against CD146.
Overall, the findings suggest that anti-CD146 antibodies may identify a subgroup of SSc linked to workplace or environmental exposures to silica or other mineral dusts.
“Currently, no biologic marker exists to monitor such exposure, which can lead to late diagnosis at advanced stages of the disease. Early identification of occupational exposure is crucial for timely diagnosis and for preventing further exposure once diagnosed,” the team wrote. “Workers testing positive for these antibodies might benefit from enhanced monitoring to detect potential occupational diseases early or to promptly cease exposure.”
