Association of HLA-DRB1 shared epitope alleles and immune checkpoint inhibitor-induced inflammatory arthritis

Cappelli, Laura C.; Dorak, M. Tevfik; Bettinotti, María P.; Bingham, Clifton O.; Shah, Ami A.

doi:10.1093/rheumatology/key358

Cited by 86 publications

(66 citation statements)

References 26 publications

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“…30,31,33,36,[57][58][59]66,[109][110][111][112][113][114][115] In a study comparing ICI-IA patients to ethnically matched counterparts with RA, 7.7% of ICI-IA patients were positive for RF or ACPAs, whereas 64.6% of RA patients were positive for ACPAs and 56.7% positive for RF, with 49.3% being positive for both. 116 Although these results indicate that the prevalence of seropositivity in ICI-IA is much lower than in RA, it is unknown if seropositivity is increased in patients who develop RA-like disease following ICI therapy.…”

Section: Ici-ia Autoantibodiesmentioning

confidence: 84%

“…A 2019 study by Cappelli et al analyzed the HLA allele frequencies in 26 patients with ICI-IA. 116 They found that having at least one RA-associated SE allele increased the probability of developing ICI-IA compared to the control population (P = .04, OR 2.3, 95% CI = 1.0-5.1). The SE allele HLA DRB1*04:05…”

Section: Ici-ia Genetic Associationsmentioning

confidence: 96%

“…Given that the mechanism of action of ICI therapy is focused on the interaction between T cells and their targets, an interaction requiring recognition of a specific peptide bound to an MHC molecule, it may be expected that individuals who possess RA‐ or SpA‐associated HLA alleles may be at increased risk for developing IA post‐treatment with ICI therapy. A 2019 study by Cappelli et al analyzed the HLA allele frequencies in 26 patients with ICI‐IA . They found that having at least one RA‐associated SE allele increased the probability of developing ICI‐IA compared to the control population ( P = .04, OR 2.3, 95% CI = 1.0‐5.1).…”

Section: Geneticsmentioning

confidence: 97%

“…Despite these limitations, aggregation of the data from multiple studies reveals a low rate of seropositivity among patients developing IA following treatment with ICI therapy with 5.5% (12/217; range 0%‐36%) positive for RF and 5% (11/217; range 0%‐11%) positive for ACPAs . In a study comparing ICI‐IA patients to ethnically matched counterparts with RA, 7.7% of ICI‐IA patients were positive for RF or ACPAs, whereas 64.6% of RA patients were positive for ACPAs and 56.7% positive for RF, with 49.3% being positive for both . Although these results indicate that the prevalence of seropositivity in ICI‐IA is much lower than in RA, it is unknown if seropositivity is increased in patients who develop RA‐like disease following ICI therapy.…”

Section: Serologymentioning

confidence: 99%

“…In another study, the SE allele HLA DRB1*01:01 was found in two out of nine patients who had inflammatory arthritis after treatment with an ICI; however, comparison to a control population was not reported . Interestingly, several studies have shown that SpA‐associated HLA‐B27 alleles do not appear to confer increased risk for ICI‐IA, as almost all patients who developed ICI‐IA were HLA‐B27‐negative . The genetic studies performed thus far show that SE alleles, but not HLA‐B27 alleles, associate with ICI‐IA.…”

Section: Geneticsmentioning

confidence: 99%

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Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis

Cappelli¹,

Thomas²,

Bingham³

et al. 2020

Immunological Reviews

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The development of inflammatory arthritis in patients receiving immune checkpoint inhibitor therapy is increasingly recognized due to the growing use of these drugs for the treatment of cancer. This represents an important opportunity not only to define the mechanisms responsible for the development of this immune‐related adverse event and to ultimately predict or prevent its development, but also to provide a unique window into early events in the development of inflammatory arthritis. Knowledge gained through the study of this patient population, for which the inciting event is known, could shed light into the pathogenesis of autoimmune arthritis. This review will highlight the clinical and immunologic features of these entities to define common elements for future study.

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Section: Ici-ia Autoantibodiesmentioning

confidence: 84%

Section: Ici-ia Genetic Associationsmentioning

confidence: 96%

Section: Geneticsmentioning

confidence: 97%

Section: Serologymentioning

confidence: 99%

Section: Geneticsmentioning

confidence: 99%

See 3 more Smart Citations

Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis

Cappelli¹,

Thomas²,

Bingham³

et al. 2020

Immunological Reviews

View full text Add to dashboard Cite

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Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications

Cappelli

Bingham

2021

Arthritis & Rheumatology

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Rheumatologists increasingly receive consults for patients treated with immune checkpoint inhibitors (ICIs) for cancer. ICIs can cause inflammatory syndromes known as immune-related adverse events (IRAEs). Several rheumatic IRAEs have been reported, including inflammatory arthritis, polymyalgia rheumatica, and myositis. For patients who present with musculoskeletal symptoms while receiving ICI therapy, it is important to have an algorithm for evaluation. The differential diagnosis includes a range of musculoskeletal syndromes, such as crystalline arthritis, mechanical issues, and osteoarthritis, in addition to IRAEs. After diagnosing a rheumatic IRAE, rheumatologists must work with the patient and the oncologist to form a treatment plan. Treatment of IRAEs is guided by severity. Evidence for management is limited to observational studies. Inflammatory arthritis and polymyalgia rheumatica are treated with nonsteroidal antiinflammatory drugs in mild cases, glucocorticoids for moderate-to-severe cases, and sometimes require other disease-modifying antirheumatic drugs. Myositis due to ICIs can be accompanied by myocarditis or myasthenia gravis. Glucocorticoids and withholding the ICI are usually required to treat myositis; some patients with severe myositis require intravenous immunoglobulin or plasmapheresis. Further research is needed to optimize treatment of IRAEs that does not compromise the antitumor effect of ICIs. Clinical challenge You receive a consult from a local oncologist. A 65-yearold man with a history of knee osteoarthritis (OA) who had previously undergone total joint arthroplasty of the left knee and is being treated with nivolumab (anti-programmed death 1 [anti-PD-1] monoclonal antibody) for non-small cell lung cancer has new symptoms of severe aching in his arms and legs, with limited mobility. The oncologist does not localize symptoms to the joints and/or muscles but notes that the patient is having trouble doing chores around the house such as cleaning and cooking.

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Immune‐related adverse events in non‐small cell lung cancer: Occurrence, mechanisms and therapeutic strategies

Lin,

Xie,

Yao

et al. 2024

Clinical & Translational Med

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The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non‐small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune‐related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ‐specific irAEs in patients with NSCLC and provide an in‐depth analysis of recent advancements in understanding the mechanisms driving ICI‐induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

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Association of HLA-DRB1 shared epitope alleles and immune checkpoint inhibitor-induced inflammatory arthritis

Cited by 86 publications

References 26 publications

Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis

Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis

Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications

Immune‐related adverse events in non‐small cell lung cancer: Occurrence, mechanisms and therapeutic strategies

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