Search

This document is a letter to the editor in response to a previous letter discussing the value of a novel diagnostic method for autoinflammatory diseases. The authors express gratitude for the positive comments and explain that their initial study used well-characterized patients with autoinflammatory, autoimmune, and infectious diseases to present solid data. They acknowledge the need for further research and validation in different pathological conditions, including tumors. The authors state that their results have motivated them to expand the study and compile a large-scale study for a broad spectrum of inflammatory phenotypes. They declare no conflicts of interest and state that no datasets were generated or analyzed during the current study. [Extracted from the article]

Objectives: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multimarker algorithm in temporal artery biopsies (TABs) of GCA patients., Methods: 75(+) TABs from GCA patients, 22(-) TABs from polymyalgia rheumatica (PMR) patients and 10(-) TABs from non-GCA/non-PMR patients were retrospectively retrieved and analysed. Synovial tissue specimens from patients with inflammatory arthritis and aorta tissue were used as disease control samples. Senescent cells and their histological origin were identified with specific cellular markers; IL-6 and MMP-9 were investigated as components of the senescent associated secretory phenotype by triple costaining. GCA or PMR artery culture supernatants were applied to fibroblasts, HUVECs and monocytes with or without IL-6R blocking agent to explore the induction of IL-6-associated cellular senescence., Results: Senescent cells were present in GCA arteries at higher proportion compared with PMR (9.50% vs 2.66%, respectively, p<0.0001) and were mainly originated from fibroblasts, macrophages and endothelial cells. IL-6 was expressed by senescent fibroblasts, and macrophages while MMP-9 by senescent fibroblasts only. IL-6(+) senescent cells were associated with the extension of vascular inflammation (transmural inflammation vs adventitia limited disease: 10.02% vs 4.37%, respectively, p<0.0001). GCA but not PMR artery culture supernatant could induce IL-6-associated senescence that was partially inhibited by IL-6R blockade., Conclusions: Senescent cells with inflammatory phenotype are present in GCA arteries and are associated with the tissue inflammatory bulk, suggesting a potential implication in disease pathogenesis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate pulmonary and small airway function in patients with idiopathic inflammatory myopathies (IIM) and make comparisons between patients with and without interstitial lung disease (ILD)., Methods: Newly diagnosed IIM patients with and without ILD determined by high resolution computed tomography were included in the study. Pulmonary and small airway function was assessed by spirometry, diffusing capacity for carbon monoxide (DLCO), body plethysmography, single and multiple breath nitrogen washout, impulse oscillometry and measurement of respiratory resistance by the interrupter technique (Rint) using the Q-box system. We used discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography to evaluate for small airway dysfunction., Results: Study cohort comprised of 26 IIM patients, 13 with and 13 without ILD. IIM-ILD patients presented more frequently with dyspnoea, fever, arthralgias and positive anti-synthetase antibodies, compared to IIM patients without ILD. Classic spirometric parameters and most lung physiology parameters assessing small airway function did not differ between the two groups. Predicted total lung capacity and residual volume (TLCN2WO, RVN2WO) measured by multiple breath nitrogen washout and the TLCN2WO/TLCpleth ratio were significantly lower in IIM-ILD patients compared to those without ILD (mean: 111.1% vs. 153.4%, p=0.034, median: 171% vs. 210%, p=0.039 and median: 1.28 vs. 1.45, p=0.039, respectively). Rint tended to be higher among IIM-ILD patients (mean:100.5% vs. 76.6%, p=0.053)., Conclusions: Discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography in IIM-ILD patients indicate an early small airways dysfunction in these patients.