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Background: Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2 LD ) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc., Objective: We aimed to assess the safety and biological efficacy of IL-2 LD in patients with SSc., Methods: As part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)/day of IL-2 for 5 days, followed by fortnightly injections for 6 months. Laboratory and clinical evaluations were performed between baseline and month 6., Results: At day 8, the primary endpoint (Treg frequency) was reached with a 1.8±0.5-fold increase of Treg levels among CD4 + T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2 LD was well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period., Conclusion: IL-2 LD at a dosage of 1 MIU/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2 LD therapeutic efficacy in SSc., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aimed to analyse the association between infections and the subsequent risk of giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) by a systematic review and a meta-analysis of observational studies., Methods: Two databases (Medline and Embase) were systematically reviewed. Epidemiological studies studying the association between any prior infection and the onset of GCA/PMR were eligible. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Outcomes and pooled statistics were reported as OR and their 95% CI., Results: Eleven studies (10 case-control studies and one cohort study) were analysed, seven of them were included in the meta-analysis. Eight were at low risk of bias. A positive and significant association was found between prior overall infections and prior Herpes Zoster (HZ) infections with pooled OR (95% CI) of 1.27 (1.18 to 1.37) and 1.20 (1.08 to 1.21), respectively. When analysed separately, hospital-treated and community-treated infections, were still significantly associated with the risk of GCA, but only when infections occurring within the year prior to diagnosis were considered (pooled OR (95% CI) 1.92 (1.67 to 2.21); 1.67 (1.54 to 1.82), respectively). This association was no longer found when infections occurring within the year prior to diagnosis were excluded., Conclusion: Our study showed a positive association between the risk of GCA and prior overall infections (occurring in the year before), and prior HZ infections. Infections might be the reflect of an altered immunity of GCA patients or trigger the disease. However, reverse causation cannot be excluded.CRD42023404089., Competing Interests: Competing interests: LP, FB and YN declare no competing interests. RS received consulting fees from GSK, Bristol Myer Squib, Boerhinger and Janssen; honoraria from GSK, Bristol Myer Squib, Boehringer, Amgen, Pfizer and Roche; travel fees from Amgen and GSK; none of this links are related to the topic of this study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)