Early Increase of Circulating Transitional B Cells and Autoantibodies to Joint-Related Proteins in Patients With Metastatic Melanoma Developing Checkpoint Inhibitor-Induced Inflammatory Arthritis

Mariele Gatto; Sara Bjursten; Charlotte A Jonsson; Monica Leu Agelii; Caroline Jonell; Sarah McGrath; Erik Lönnblom; Outi Sareila; Rikard Holmdahl; Anna Rudin; Max Levin; Inger Gjertsson

doi:10.1002/art.42406

Early Increase of Circulating Transitional B Cells and Autoantibodies to Joint-Related Proteins in Patients With Metastatic Melanoma Developing Checkpoint Inhibitor-Induced Inflammatory Arthritis

Arthritis Rheumatol. 2023 May;75(5):856-863. doi: 10.1002/art.42406. Epub 2023 Mar 14.

Authors

Affiliations

¹ Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, and Department of Medicine, Unit of Rheumatology, University of Padova, Italy.
² Department of Oncology, Sahlgrenska University Hospital, and Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Medical Biochemistry and Biophysics, Section for Medical Inflammation Research, Karolinska Institute, Stockholm, Sweden.
⁵ Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, and Wallenberg Laboratory for Cardiovascular Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

PMID: 36409578
DOI: 10.1002/art.42406

Abstract

Objective: To investigate potential associations between B cell-related immunologic changes and development of inflammatory arthritis (IA) after treatment with immune checkpoint inhibitors (ICIs).

Methods: Patients who developed ICI-induced IA (ICI-IA) and patients who did not develop immune-related adverse events (non-IRAE) after receiving ICIs to treat metastatic melanoma were consecutively recruited. Blood samples were collected at the time of ICI-IA occurrence and at different time points during treatment. Peripheral blood B cell subsets during ICI treatment were analyzed by flow cytometry. Rheumatoid factor, anti-citrullinated protein antibodies, and antibodies against joint-related proteins were measured.

Results: Proportions of CD19+ B cells were higher in patients with ICI-IA (n = 7) compared to patients with non-IRAE (n = 15) (median 11.7% [interquartile range (IQR) 9.7-16.2%] versus 8.1% [IQR 5.7-11.0%]; P = 0.03). The proportion and absolute numbers of transitional CD19+CD10+CD24^high CD38^high B cells were increased in patients with ICI-IA compared to non-IRAE patients (median 8.1% [IQR 4.9-12.1%] versus 3.6% [IQR 1.9-4.9%]; median 10.7 cells/μl [IQR 8.9-19.6] versus 4.4 cells/μl [IQR 2.3-6.6]; P < 0.01 for both). In addition, higher levels of transitional B cells were associated with development of ICI-IA (odds ratio 2.25 [95% confidence interval 1.03-4.9], P = 0.04). Transitional B cells increased before the onset of overt ICI-IA and decreased between the active and quiescent stages of ICI-IA (P = 0.02). Autoantibodies to type II collagen epitopes were detected in up to 43% of ICI-IA patients compared to none of the non-IRAE patients (P = 0.02).

Conclusion: Development of ICI-IA is accompanied by an increase in transitional B cells and by production of autoantibodies to joint-related proteins. Monitoring of B cell-driven abnormalities upon ICI treatment may help earlier recognition of ICI-IA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis* / etiology
Autoantibodies
Humans
Immunotherapy / adverse effects
Melanoma* / drug therapy
Precursor Cells, B-Lymphoid

Substances

Autoantibodies