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

Abstract

ObjectivePatients with inflammatory arthritis (IA) associated with immune checkpoint inhibitor (ICI) treatment for cancer are typically seronegative for anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factor, but little is known about the presence of other autoantibodies in this patient population. We investigated the prevalence and characteristics of anti-RA33 antibodies in patients with ICI-induced IA.MethodsAnti-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 level, clinical and demographic data were compared across groups.ResultsAnti-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 patients positive for anti-RA33, two had sera available from before ICI treatment; anti-RA33 antibodies were present in both pre-ICI treatments. In patients with RA, 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.ConclusionsAnti-RA33 antibodies are present in a subset of patients with ICI-induced IA, absent in other ICI-treated patients 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.

Rheumatoid arthritis as a clinical and immunological syndrome: focus on the seronegative subtype of the disease

“…2023;61(3):276-291 энтезита, энтезопатии, аксиального воспаления и псориатического поражения кожи, характерных для СпА [180][181][182][183][184]. В сыворотках пациентов были обнаружены анти-РA33 [185], которые, как уже отмечалось, выявляются у пациентов с серонегативным РА [89]. Являются ли анти-PA33 биомаркером особого субтипа серонегативного РА, патогенетически связанного с ингибицией CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), в настоящее время не известно.…”

Seronegative rheumatoid arthritis: one year in review 2023

“…It is interesting to mention that signs of B cell activation and antibody production have also been recently described in the classical seronegative arthitides arising in course of ICIs. Cappelli et al (40) showed that more than 11% of patients with seronegative ICI-induced arthritis had anti-RA33 antibodies, whereas none of the patients not developing arthritis had these antibodies. Similarly, a significant increase in transitional B cells and specific autoantibodies to joint-related proteins was documented in a prospective cohort of patients treated with ICI for melanoma who developed inflammatory arthritis (41).…”

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update

“…In contrast, according to a study by Cappelli, anti-RA33 antibodies were detected in 11.4% of patients with ICI-induced arthritis, whereas none of the ICI-treated controls without arthritis tested positive [ 88 ]. The antibodies were also present in 7.7% of patients with RA and 2% of healthy controls, suggesting that autoantibodies may play a role in ICI-induced arthritis or that individuals with pre-existing autoantibodies are at risk of ICI-induced arthritis.…”