Anti-RA33 antibodies are present in a subset of patients with immune checkpoint inhibitor-induced inflammatory arthritis

Abstract Background Patients with inflammatory arthritis (IA) associated with immune checkpoint inhibitor (ICI) treatment for cancer are typically seronegative for anti-CCP antibodies and rheumatoid factor, but little is known about the presence of other autoantibodies described in early inflammatory arthritis in this patient population. We investigated the prevalence and characteristics of anti-RA33 antibodies in patients with ICI-induced IA. Methods Anti-RA33 ELISAs were performed on sera from four groups of patients: 79 with ICI-induced IA, 52 with rheumatoid arthritis (RA), 35 treated with ICIs without IA during follow-up, and 50 healthy controls. Anti-RA33 positivity and titer, clinical and demographic data were compared across groups. Results Anti-RA33 antibodies were found in 9/79 (11.4%) patients with ICI-induced IA but in 0/35 patients treated with ICIs who did not develop IA (0%; p=0.04). Of the 9 patients positive for anti-RA33, two had sera available from before ICI treatment; anti-RA33 antibodies were present in both pre-ICI treatment. In RA patients, 7.7% were positive for anti-RA33 antibodies as were 2% of healthy controls. In ICI-induced IA, anti-RA33 antibodies were associated with anti-CCP antibodies (p=0.001). We found no statistically significant differences in other clinical characteristics in those with and without anti-RA33 antibodies, but we observed trends toward anti-RA33 antibodies being more common in women and those receiving prior radiation therapy. Conclusions Anti-RA33 antibodies are present in a subset of patients with ICI-induced IA and may be a biomarker for developing IA. Additional studies evaluating serial samples before and after ICI treatment will further establish the temporal relationship of these antibodies to IA development.