New research presented at the American Thoracic Society 2025 International Conference may indicate certain protein and pathway differences that could represent opportunities to intervene in idiopathic inflammatory myopathy (IIM) to prevent the development of interstitial lung disease (ILD).
Anti-Jo-1 antibody is a myositis-specific autoantibody often found in patients with IIM. “Myositis-specific autoantibodies are essential for diagnosing IIM and identifying patient subgroups at high risk for ILD,” wrote the authors, led by Julio A. Huapaya, MD, of the National Heart, Lung, and Blood Institute, National Institutes of Health, in Bethesda, Maryland.
“We investigated the proteomic profiles of anti-Jo-1 IIM patients to identify unique proteins and biological pathways that distinguish this group from IIM patients who rarely develop ILD and healthy controls.”
The researchers used mass spectrometry to analyze peripheral blood samples from 15 patients with IIM who were Jo-1-positive, 12 of whom had ILD. They compared those results to those from 15 IIM patients who were Jo-1-negative and matched for age and gender, as well as 10 healthy controls.
The anti-Jo-1 patients had 176 overexpressed and 65 underexpressed proteins compared to healthy controls. They had “a distinct plasma proteomic profile with overexpression of proteins linked to cellular stress, neutrophil degranulation, immune response, and tissue repair,” the authors wrote. Those patients also showed underexpression of proteins related to coagulation and immune cell activity. On the other hand, non-Jo-1 patients had 260 significantly overexpressed and 299 underexpressed proteins compared to healthy controls. Overexpressions were in proteins related to muscle function, membrane trafficking, and angiogenesis.
Patients with Jo-1 had higher expression of cell signaling/regulation proteins, antioxidant proteins, and cytoskeletal proteins compared to the non-Jo1 participants. Both groups of patients with IIM overexpressed inflammatory chemokines, ribosomal proteins, and cytoskeletal proteins.
The authors concluded that these differences in protein expression may provide clues for future therapeutic targets.
Reference
American Thoracic Society International Conference. Abstract #A5249. https://www.atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A5249.
