Soluble Co‐Inhibitory Immune Checkpoint Molecules Are Increased in Patients With Polymyalgia Rheumatica Without Significant Correlations With Clinical Status: A Case‐Control Study
Objective A dysregulated immune response is involved in the pathogenesis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). These diseases have been reported as immune‐related adverse events in patients with cancer treated with immune checkpoints inhibitors. In this cross‐sectional stud...
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Wiley
2025-05-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.70045 |
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| author | Elvis Hysa Dario Camellino Christian Dejaco Matteo Bauckneht Giampaola Pesce Silvia Morbelli Marcello Bagnasco Maurizio Cutolo Eric L. Matteson Marco A. Cimmino Daniele Saverino |
| author_facet | Elvis Hysa Dario Camellino Christian Dejaco Matteo Bauckneht Giampaola Pesce Silvia Morbelli Marcello Bagnasco Maurizio Cutolo Eric L. Matteson Marco A. Cimmino Daniele Saverino |
| author_sort | Elvis Hysa |
| collection | DOAJ |
| description | Objective A dysregulated immune response is involved in the pathogenesis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). These diseases have been reported as immune‐related adverse events in patients with cancer treated with immune checkpoints inhibitors. In this cross‐sectional study, the relationship between soluble immune checkpoint molecules (sICMs) and clinical/imaging features of PMR and GCA was investigated. Methods Consecutive patients with PMR diagnosed according to the criteria by Bird et al were compared with age‐ and sex‐matched healthy controls. Patients with PMR and overlapping GCA had to also satisfy the 1990 ACR classification criteria for GCA. All patients underwent standardized clinical, laboratory examination, and 18F‐fluorodeoxyglucose positron emission tomography/computed tomography scans. The sICM anticytotoxic T Ly‐4, the programmed cell death protein 1 (PD‐1), and PD‐1 ligands PD‐L1 and PD‐L2 were measured by enzyme‐linked immunosorbent assay. Results Forty patients (80% women, mean age 76 years, and mean disease duration 88 days) were assessed. Of these, 30 had isolated PMR and 10 had PMR with GCA. Patients showed significantly higher concentrations of all sICMs compared with controls (P < 0.001). Conditional logistic regression revealed the strong discriminative capacity of these molecules between patients and healthy controls, with PD‐1 showing complete separation among groups (effect size = 0.78) and PD‐L1 (odds ratio [OR] 134.33, P < 0.001) and PD‐L2 (OR 63.00, P < 0.001) demonstrating the strongest ability to distinguish patients from controls. Correlations between sICM levels and clinical features were generally weak or absent, with no significant differences based on disease phenotype or glucocorticoid exposure. Results were similar in glucocorticoid‐naive patients. Conclusion sICMs are significantly elevated in PMR and GCA and strongly differentiate patients from healthy controls. Although they do not correlate with clinical or imaging features, their consistent elevation in active disease might suggest a complex interplay between innate and adaptive immunity. |
| format | Article |
| id | doaj-art-7cbb04cebfb2427591d5a8adfe829069 |
| institution | DOAJ |
| issn | 2578-5745 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
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| series | ACR Open Rheumatology |
| spelling | doaj-art-7cbb04cebfb2427591d5a8adfe8290692025-08-20T03:21:50ZengWileyACR Open Rheumatology2578-57452025-05-0175n/an/a10.1002/acr2.70045Soluble Co‐Inhibitory Immune Checkpoint Molecules Are Increased in Patients With Polymyalgia Rheumatica Without Significant Correlations With Clinical Status: A Case‐Control StudyElvis Hysa0Dario Camellino1Christian Dejaco2Matteo Bauckneht3Giampaola Pesce4Silvia Morbelli5Marcello Bagnasco6Maurizio Cutolo7Eric L. Matteson8Marco A. Cimmino9Daniele Saverino10Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Department of Experimental Medicine (DIMES), University of Genova Genova ItalyDIMES, University of Genova, Division of Rheumatology, “La Colletta” Hospital, Local Health Trust 3 Genova ItalyDepartment of Rheumatology and Immunology, Medical University of Graz, Graz, Austria, and Department of Rheumatology, Hospital of Brunico (SABES‐ASDAA), Department of Rheumatology, Teaching Hospital of the Paracelsus Medical University Brunico ItalyNuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Department of Health Sciences, University of Genova Genova ItalyDepartment of Internal Medicine, Immunology Unit, University of Genova, Diagnostic Laboratory of Autoimmunology, IRCSS Ospedale Policlinico San Martino Genova ItalyNuclear Medicine Unit, Department of Medical Sciences University of Turin Turin ItalyDepartment of Internal Medicine and Medical Specialties University of Genova Genova ItalyLaboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine University of Genova, IRCSS Ospedale Policlinico San Martino Genova ItalyMayo Clinic College of Medicine and Science Rochester MinnesotaLaboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine University of Genova Genova ItalyDIMES, University of Genova, Diagnostic Laboratory of Autoimmunology IRCSS Ospedale Policlinico San Martino Genova ItalyObjective A dysregulated immune response is involved in the pathogenesis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). These diseases have been reported as immune‐related adverse events in patients with cancer treated with immune checkpoints inhibitors. In this cross‐sectional study, the relationship between soluble immune checkpoint molecules (sICMs) and clinical/imaging features of PMR and GCA was investigated. Methods Consecutive patients with PMR diagnosed according to the criteria by Bird et al were compared with age‐ and sex‐matched healthy controls. Patients with PMR and overlapping GCA had to also satisfy the 1990 ACR classification criteria for GCA. All patients underwent standardized clinical, laboratory examination, and 18F‐fluorodeoxyglucose positron emission tomography/computed tomography scans. The sICM anticytotoxic T Ly‐4, the programmed cell death protein 1 (PD‐1), and PD‐1 ligands PD‐L1 and PD‐L2 were measured by enzyme‐linked immunosorbent assay. Results Forty patients (80% women, mean age 76 years, and mean disease duration 88 days) were assessed. Of these, 30 had isolated PMR and 10 had PMR with GCA. Patients showed significantly higher concentrations of all sICMs compared with controls (P < 0.001). Conditional logistic regression revealed the strong discriminative capacity of these molecules between patients and healthy controls, with PD‐1 showing complete separation among groups (effect size = 0.78) and PD‐L1 (odds ratio [OR] 134.33, P < 0.001) and PD‐L2 (OR 63.00, P < 0.001) demonstrating the strongest ability to distinguish patients from controls. Correlations between sICM levels and clinical features were generally weak or absent, with no significant differences based on disease phenotype or glucocorticoid exposure. Results were similar in glucocorticoid‐naive patients. Conclusion sICMs are significantly elevated in PMR and GCA and strongly differentiate patients from healthy controls. Although they do not correlate with clinical or imaging features, their consistent elevation in active disease might suggest a complex interplay between innate and adaptive immunity.https://doi.org/10.1002/acr2.70045 |
| spellingShingle | Elvis Hysa Dario Camellino Christian Dejaco Matteo Bauckneht Giampaola Pesce Silvia Morbelli Marcello Bagnasco Maurizio Cutolo Eric L. Matteson Marco A. Cimmino Daniele Saverino Soluble Co‐Inhibitory Immune Checkpoint Molecules Are Increased in Patients With Polymyalgia Rheumatica Without Significant Correlations With Clinical Status: A Case‐Control Study ACR Open Rheumatology |
| title | Soluble Co‐Inhibitory Immune Checkpoint Molecules Are Increased in Patients With Polymyalgia Rheumatica Without Significant Correlations With Clinical Status: A Case‐Control Study |
| title_full | Soluble Co‐Inhibitory Immune Checkpoint Molecules Are Increased in Patients With Polymyalgia Rheumatica Without Significant Correlations With Clinical Status: A Case‐Control Study |
| title_fullStr | Soluble Co‐Inhibitory Immune Checkpoint Molecules Are Increased in Patients With Polymyalgia Rheumatica Without Significant Correlations With Clinical Status: A Case‐Control Study |
| title_full_unstemmed | Soluble Co‐Inhibitory Immune Checkpoint Molecules Are Increased in Patients With Polymyalgia Rheumatica Without Significant Correlations With Clinical Status: A Case‐Control Study |
| title_short | Soluble Co‐Inhibitory Immune Checkpoint Molecules Are Increased in Patients With Polymyalgia Rheumatica Without Significant Correlations With Clinical Status: A Case‐Control Study |
| title_sort | soluble co inhibitory immune checkpoint molecules are increased in patients with polymyalgia rheumatica without significant correlations with clinical status a case control study |
| url | https://doi.org/10.1002/acr2.70045 |
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