Anti-Sp4 and anti-CCAR1 autoantibodies in UK vs US patients with adult and juvenile-onset anti-TIF1γ-γpositive myositis

Abstract

Objectives: Anti-transcriptional intermediary factor 1γ (TIF1γ) autoantibodies are associated with malignancy in adult-onset idiopathic inflammatory myopathy (IIM) and this risk is attenuated if patients are also positive for anti-specificity protein 4 (Sp4) or anti-cell division cycle apoptosis regulator protein 1 (CCAR1). In anti-TIF1γ positive dermatomyositis (DM) patients from the USA, anti-Sp4 and anti-CCAR1 autoantibody frequencies are reported as 32% and 43% in adults and 9% and 19% in juveniles, respectively. This study aims to identify the frequency of anti-Sp4 and anti-CCAR1 in adult and juvenile UK anti-TIF1γ-positive myositis populations and report clinical associations. Methods: Serum samples from 51 UK participants with adult-onset IIM and 55 UK participants with JDM, all anti-TIF1γ autoantibody positive, and 24 healthy control samples were screened for anti-Sp4 and anti-CCAR1 autoantibodies by ELISA. Results: In UK adult anti-TIF1γ positive IIM patients, anti-Sp4 and anti-CCAR1 frequencies were 4% (2/51) and 16% (8/51). Both adult patients with anti-Sp4 were also positive for anti-CCAR1. In UK juveniles, anti-Sp4 was not detected and 13% (7/55) had anti-CCAR1 autoantibodies. Nineteen (37%) anti-TIF1γ positive UK adult myositis patients had cancer; neither of the two patients with anti-Sp4 autoantibodies and 25% (2/8) of anti-CCAR1 autoantibody-positive patients had cancer. No anti-Sp4 or anti-CCAR1 clinical associations were identified. Conclusion: Anti-Sp4 and anti-CCAR1 autoantibodies are less common in the adult UK anti-TIF1γ-positive myositis population compared with published data from the USA, limiting their use as biomarkers for cancer risk. In patients with juvenile onset disease, anti-Sp4 is less frequent in UK patients compared with the USA, but the prevalence of anti-CCAR1 autoantibodies is similar.