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Immune complex-mediated neutrophil activation in patients with polymyalgia rheumatica
Division of Rheumatology, Department of Medicine, University of Washington, WA, Seattle, United States.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
Division of Rheumatology, Department of Medicine, University of Washington, WA, Seattle, United States; Center of Life Sciences, Mahindra University, Hyderabad, India.
Division of Rheumatology, Department of Medicine, University of Washington, WA, Seattle, United States.
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2023 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 62, no 8, p. 2880-2886Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Neutrophils are important in host defence. However, neutrophils are also linked to inflammation and organ damage. The purpose of this study was to assess whether markers of neutrophil activation are increased in PMR.

METHODS: Levels of immune complexes (IC), calprotectin and neutrophil extracellular traps (NETs) were measured in plasma of healthy individuals (n = 30) and patients with PMR (n = 60), at flare and upon treatment with glucocorticoids using ELISA. Plasma-mediated neutrophil activation was assessed in presence of an FcγRIIA inhibitory antibody (IV.3).

RESULTS: Plasma levels of calprotectin and NETs were elevated in PMR (P < 0.001). Mechanistically, neutrophil activation was driven by ICs, present in plasma, able to up-regulate neutrophil activation markers CD66b and CD11b (P < 0.0001) in an FcγRIIA-dependent manner (P < 0.01). Of note, circulating levels of IC correlated with plasma induced CD66b and CD11b (r = 0.51, P = 0.004, and r = 0.46, P = 0.01, respectively) and decreased after glucocorticoid therapy. In contrast to NETs, calprotectin significantly decreased after glucocorticoid therapy (P < 0.001) and was higher in PMR without overlapping GCA compared with patients with overlapping disease (P = 0.014). Interestingly, musculoskeletal involvement was associated with elevated levels of calprotectin before initiation of glucocorticoid therapy (P = 0.036).

CONCLUSIONS: Neutrophil activation, including NET formation, is increased in PMR, through IC-mediated engagement of FcγRIIA. Clinically, neutrophil activation is associated with musculoskeletal involvement, with calprotectin, but not NETs, being a biomarker of treatment response in PMR patients. In all, IC-mediated neutrophil activation is a central process in PMR pathogenesis identifying potential novel therapeutic targets (FcγRIIA), as well as soluble markers for disease monitoring (calprotectin).

Place, publisher, year, edition, pages
Oxford University Press, 2023. Vol. 62, no 8, p. 2880-2886
Keywords [en]
calprotectin, immune complexes, neutrophil extracellular traps, neutrophils, PMR
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-212736DOI: 10.1093/rheumatology/keac722ISI: 000908331800001PubMedID: 36562570Scopus ID: 2-s2.0-85162077877OAI: oai:DiVA.org:umu-212736DiVA, id: diva2:1787703
Available from: 2023-08-14 Created: 2023-08-14 Last updated: 2023-08-14Bibliographically approved

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Johansson, LindaRantapää-Dahlqvist, Solbritt

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