A novel autoantibody targeting calreticulin is associated with cancer in patients with idiopathic inflammatory myopathies

Abstract

Objectives. To investigate the prevalence and clinical significance of anti-calreticulin autoantibodies (anti-CRT Ab) in a large cohort of idiopathic inflammatory myopathy (IIM) patients. Methods. Sera from 469 patients with IIM, 196 patients with other connective tissue diseases, 28 patients with solid tumors and 81 healthy controls were screened for anti-CRT Ab by enzyme-linked immunosorbent assay using human recombinant CRT protein. Sera from 35 IIM patients were tested using an immunoprecipitation assay to confirm the presence of anti-CRT Ab. Subsequently, IIMcancer patients were identified and divided into new-onset, remission and recurrent groups based on their cancer status. The relationships between anti-CRT Ab levels and IIM disease activity were also investigated. Results. Serum anti-CRT Ab was detected positive in 81 of the 469 (17.3%) IIM patients. Immunoprecipitated bands were observed at a molecular weight of 60 kDa corresponding to the CRT protein. The IIM patients with anti-CRT Ab more frequently had cancers compared to the patients without anti-CRT Ab. Moreover, the prevalence of anti-CRT Ab differed according to the cancer status. The IIM patients with recurrent cancers had a much higher prevalence of anti-CRT Ab than those with cancers in remission. Also, serum anti-CRT Ab levels positively correlated with disease activity at baseline and at follow-up visits. Conclusion. We report the existence of serum anti-CRT Ab in IIM patients and demonstrate the possible association of anti-CRT Ab with malignancy in IIM patients. Serum anti-CRT Ab could serve as a novel candidate marker of cancer in IIM patients.

Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetes

“…Calreticulin resides in the lumen of the endoplasmic reticulum and performs two main functions, Ca 2+ binding and protein chaperoning, a function clearly impaired in CF, a protein misfolding disease ( 139 ). Anti-calreticulin autoantibodies were reported in a cohort of idiopathic inflammatory myopathy patients and associated with malignancy ( 140 ). IgM autoantibodies targeting catalase could diminish the antioxidant potential in the airways and promote oxidative stress-mediated lung disease in CF ( 141 ).…”

Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?

“…One study of DM patients documented the presence of anti-SRP72 antibodies ( 163 ). Recently, a possible association between anti-calreticulin (anti-CRT) antibodies and malignancy in IIM was reported ( 164 ).…”