Early Increase of Circulating Transitional B Cells and Autoantibodies to <scp>Joint‐Related</scp> Proteins in Patients With Metastatic Melanoma Developing Checkpoint Inhibitor–Induced Inflammatory Arthritis

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

doi:10.1002/art.42406

Cited by 5 publications

(3 citation statements)

References 44 publications

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“…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). Altogether, these finding point at an autoimmune contribution to disease pathogenesis also in a set of conditions traditionally considered seronegative.…”

Section: Novel Antibodiesmentioning

confidence: 71%

Seronegative rheumatoid arthritis: one year in review 2023

Stefano

D’Onofrio

Gandolfo

et al. 2023

Clinical and Experimental Rheumatology

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In the past 20 years, earlier diagnosis and more intensive management have considerably improved the prognosis of rheumatoid arthritis (RA), with milder disease course achieved in particular in seropositive patients. In contrast, seronegative RA has remained largely neglected, and continues to be surrounded by uncertainties regarding its correct diagnosis, clinical phenotype, optimal treatment strategies and relevant outcomes. The purpose of this review is to summarise new insights about the pathogenic, clinical and prognostic peculiarities of seronegative RA that emerged during 2022, and that make this disease subset at least partially different from its seropositive counterpart.

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Section: Novel Antibodiesmentioning

confidence: 71%

Seronegative rheumatoid arthritis: one year in review 2023

Stefano

D’Onofrio

Gandolfo

et al. 2023

Clinical and Experimental Rheumatology

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“…According to previous studies, ICI-induced arthritis has been observed in around 5% of patients treated with ICIs, exhibiting varying degrees of severity (Weinmann and pisetsky, 2019;Gatto et al, 2022). Some studies have suggested a higher incidence of arthritis with pembrolizumab (Xu et al, 2018;Ramos-Casals et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Musculoskeletal adverse events induced by immune checkpoint inhibitors: a large-scale pharmacovigilance study

Liu,

Li,

et al. 2023

Front. Pharmacol.

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Background: The musculoskeletal toxicity of immune checkpoint inhibitors (ICIs) is receiving increasing attention with clinical experience. Nevertheless, the absence of a systematic investigation into the musculoskeletal toxicity profile of ICIs currently results in the under-recognition of associated adverse events. Further and more comprehensive investigations are warranted to delineate the musculoskeletal toxicity profile of ICIs and characterize these adverse events.Material and methods: The present study employed the FDA Adverse Event Reporting System database to collect adverse events between January 2010 and March 2021. We utilized both the reporting odds ratio and the Bayesian confidence propagation neural network algorithms to identify suspected musculoskeletal adverse events induced by ICIs. Subsequently, the clinical characteristics and comorbidities of the major musculoskeletal adverse events were analyzed. The risk of causing these events with combination therapy versus monotherapy was compared using logistic regression model and Ω shrinkage measure model.Results: The musculoskeletal toxicity induced by ICIs primarily involves muscle tissue, including neuromuscular junctions, fascia, tendons, and tendon sheaths, as well as joints, spine, and bones, including cartilage. The toxicity profile of PD-1/PD-L1 and CTLA-4 inhibitors varies, wherein the PD-1 inhibitor pembrolizumab exhibits a heightened overall risk of inducing musculoskeletal adverse events. The major ICIs-induce musculoskeletal adverse events, encompassing conditions such as myositis, neuromyopathy (including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Guillain-Barré syndrome, and Chronic inflammatory demyelinating polyradiculoneuropathy), arthritis, fractures, myelitis, spinal stenosis, Sjogren’s syndrome, fasciitis, tenosynovitis, rhabdomyolysis, rheumatoid myalgia, and chondrocalcinosis. Our study provides clinical characteristics and comorbidities of the major ICIs-induced musculoskeletal adverse events. Furthermore, the combination therapy of nivolumab and ipilimumab does not result in a statistically significant escalation of the risk associated with the major musculoskeletal adverse events.Conclusion: Immune checkpoint inhibitors administration triggers a range of musculoskeletal adverse events, warranting the optimization of their management during clinical practice.

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“…Das et al 47 observed a reduction in circulating B cells in patients with melanoma after ICI therapy and that this was associated with greater risk of ICI‐induced irAEs as well as irAE severity. More recently, Gatto et al 48 reported that the frequency of transitional B cells is higher in patients that develop ICI‐induced arthritis compared to those who do not. Collectively, these studies indicate that the induction of irAEs may be seen in individuals who already have a break in B‐cell tolerance as demonstrated by pre‐treatment autoantibodies, but that ICI therapy may also promote loss of B cell tolerance, potentially through the promotion of the Tfh‐B cell axis, resulting in autoantibodies that contribute to disease or are evidence of the evolution of autoreactivity due to ICI therapy.…”

Section: Ici‐induced Iraesmentioning

confidence: 99%

Immune‐related adverse events after immune check point inhibitors: Understanding the intersection with autoimmunity

Singh

Hocking

Buckner

2023

Immunological Reviews

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SummaryImmune checkpoint inhibitor therapies act through blockade of inhibitory molecules involved in the regulation of T cells, thus releasing tumor specific T cells to destroy their tumor targets. However, immune checkpoint inhibitors (ICI) can also lead to a breach in self‐tolerance resulting in immune‐related adverse events (irAEs) that include tissue‐specific autoimmunity. This review addresses the question of whether the mechanisms that drive ICI‐induced irAEs are shared or distinct with those driving spontaneous autoimmunity, focusing on ICI‐induced diabetes, ICI‐induced arthritis, and ICI‐induced thyroiditis due to the wealth of knowledge about the development of autoimmunity in type 1 diabetes, rheumatoid arthritis, and Hashimoto's thyroiditis. It reviews current knowledge about role of genetics and autoantibodies in the development of ICI‐induced irAEs and presents new studies utilizing single‐cell omics approaches to identify T‐cell signatures associated with ICI‐induced irAEs. Collectively, these studies indicate that there are similarities and differences between ICI‐induced irAEs and autoimmune disease and that studying them in parallel will provide important insight into the mechanisms critical for maintaining immune tolerance.

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

Cited by 5 publications

References 44 publications

Seronegative rheumatoid arthritis: one year in review 2023

Seronegative rheumatoid arthritis: one year in review 2023

Musculoskeletal adverse events induced by immune checkpoint inhibitors: a large-scale pharmacovigilance study

Immune‐related adverse events after immune check point inhibitors: Understanding the intersection with autoimmunity

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