Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients.

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.

Impact of the mandatory confinement during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portuguese patients with rheumatoid arthritis: results from the COVID in RA (COVIDRA) survey.

OBJECTIVE: The aim of this study was to evaluate the self-reported impact of mandatory confinement occurring in the first wave of the SARS-CoV-2 pandemic in Portuguese patients with rheumatoid arthritis (RA), as a means to improve care during this and in future pandemics. MATERIAL AND METHODS: The web-based survey COVIDRA was developed to assess 5 domains including RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. RESULTS: We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%) with a mean age of 58 years. The majority had disease lasting >10 years and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23.7%). Over 40% experienced symptom worsening during confinement, almost half considered moderate or severe. Mobility restriction and increased stress, anxiety or depression were responsible for this worsening. Only 2.5% reduced or withheld their immunosuppressive medication due to fear of becoming infected with SARS-CoV-2. After confinement, 16.2% of those previously employed were in a lay-off regime and 3% lost their jobs. Most employed RA patients practiced telework during confinement. The majority of patients decreased or did not practice any physical exercise (80.5%). Symptoms of anxiety and depression developed or worsened in 67.3% and 51.9% respectively, approximately one third were considered moderate or severe. CONCLUSIONS: Portuguese RA patients experienced significant symptom worsening, anxiety and depression during the first wave confinement. Only a minority changed their immunosuppressive treatment for fear of SARS-CoV-2 infection. Published literature on these matters shows results very similar to ours.