[Prospective monitoring of a university rheumatology outpatient clinic throughout the first wave of the COVID-19 pandemic : What lessons can be learned?] / Prospektive Verlaufsbeobachtung einer universitären Rheumaambulanzkohorte während der ersten Welle der COVID-19-Pandemie : Welche Lehren kann man ziehen?

BACKGROUND: In March 2020 the SARS-CoV­2 pandemic disseminated initially especially in Bavaria. At that time data on patients with rheumatic diseases and immunomodulatory treatment was lacking. OBJECTIVE: The aim was to analyze the influence of the SARS-CoV­2 pandemic on the clinical treatment strategy. MATERIAL AND METHODS: Between 16 March and 31 July 2020 all patients who consecutively presented at the rheumatology outpatient clinic of the Klinikum rechts der Isar of the Technical University of Munich were included in the study. Individual treatment adjustments were based on clinical judgment and the recommendations for action of the German Society for Rheumatology (DGRh). RESULTS: A total of 322 patients were included. The most frequent diagnosis was rheumatoid arthritis with 17%, ANCA-associated vasculitis (AAV) with 14% and SLE with 12%. Of the patients 262 were on DMARD treatment and 77 received oral glucocorticoids. There were 5 cases of suspected SARS-CoV­2 infection; however, no patient verifiably became ill due to COVID-19. In 40 patients, treatment adjustments were done due to the pandemic, whereby 3 patients developed a flare of the underlying disease. In retrospect, treatment de-escalation occurred most frequently in AAV, IgG4-related disease, immunosuppressive treatment with rituximab and the simultaneous presence of malignant diseases. CONCLUSION: The total lack of confirmed SARS-CoV­2 infections in an otherwise strongly affected region could indicate that the infection risk for SARS-CoV­2 is not substantially increased for patients with inflammatory rheumatic diseases. A continuation of most immunosuppressive medications therefore seems reasonable during the ongoing pandemic.

Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis.

Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF-producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A+GM-CSF+ double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF+CD4+ cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF+ and IL-17A+GM-CSF+ double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis.

miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis.

OBJECTIVE: To determine the microRNA (miR) signature in ankylosing spondylitis (AS) T helper (Th)17 cells. METHODS: Interleukin (IL)-17A-producing CD4+ T cells from patients with AS and healthy controls were FACS-sorted for miR sequencing and qPCR validation. miR-10b function was determined by miR mimic expression followed by cytokine measurement, transcriptome analysis, qPCR and luciferase assays. RESULTS: AS Th17 cells exhibited a miR signature characterised by upregulation of miR-155-5p, miR-210-3p and miR-10b. miR-10b has not been described previously in Th17 cells and was selected for further characterisation. miR-10b is transiently induced in in vitro differentiated Th17 cells. Transcriptome, qPCR and luciferase assays suggest that MAP3K7 is targeted by miR-10b. Both miR-10b overexpression and MAP3K7 silencing inhibited production of IL-17A by both total CD4 and differentiating Th17 cells. CONCLUSIONS: AS Th17 cells have a specific miR signature and upregulate miR-10b in vitro. Our data suggest that miR-10b is upregulated by proinflammatory cytokines and may act as a feedback loop to suppress IL-17A by targeting MAP3K7. miR-10b is a potential therapeutic candidate to suppress pathogenic Th17 cell function in patients with AS.