Introduction: An over-expression of CD19 has been shown in B cells of systemic sclerosis (SSc) and B cells are thought to contribute to the induction of skin fibrosis in the tight skin mouse model. The aim was to define the outcome on safety and the change in skin score after rituximab therapy in SSc patients and to correlate the clinical characteristics with the levels of interleukin (IL)-6 and with the immune cell infiltrate detected by immunohistochemistry. Methods: Nine patients with SSc with mean age 40.9 ± 11.1 years were treated with anti-CD20, 1 g at time 0 and after 14 days. Skin biopsy was performed at baseline and during the follow-up. B-cell activating factor (BAFF) and IL-6 levels were also determined at the follow-up times. Results: After 6 months patients presented a median decrease of the skin score of 43.3% (range 21.1-64.0%), and a decrease in disease activity index and disease severity index. IL-6 levels decreased permanently during the follow up. After treatment, a complete depletion of peripheral blood B cells was observed in all but 2 patients. Only 3 patients presented CD20 positive cells in the biopsy of the involved skin at baseline. Conclusions: Anti-CD20 treatment has been well tolerated and SSc patients experienced an improvement of the skin score and of clinical symptoms. The clear fall in IL-6 levels could contribute to the skin fibrosis improvement, while the presence of B cells in the skin seems to be irrelevant with respect to the outcome after B cell depletion. Trial registration: ISRCTN77554566.

Objectives Treatment of rheumatoid arthritis (RA) should aim at full remission. The aims of this study were to define: (1) how many patients reached ultrasound power Doppler (US-PD) remission in a cohort of patients with early RA (ERA) compared with longstanding RA (LSRA); (2) possible predictors of US-PD remission; and (3) how many patients with and without US-PD remission relapsed after 1 year of follow-up in ERA and LSRA. Methods 48 patients with ERA and 46 with LSRA with disease activity score <1.6 underwent US assessment. Six hand and wrist joints were studied for active synovitis. 56.2% of patients with ERA and 50.0% of those with LSRA fulfilled American College of Rheumatology (ACR) remission criteria. Results 43.7% of patients with ERA and 17.4% of those with LSRA had no evidence of synovitis at US evaluation. Using a stricter clinical definition of remission (ie, ACR criteria), US evaluation confirmed clinical remission in 66.7% of patients with ERA and 26.1% of those with LSRA. Early disease was predictive of clinical US remission. 20.0% of patients with RA who had a negative PD signal at the US evaluation had a flare during the 12-month follow-up period compared with 47.1% of patients who had a positive PD signal. Conclusion US-PD remission occurs in half of patients with ERA and in a minority of patients with LSRA in clinical remission. Early disease seems to be the major determinant of full remission.

To assess whether, in the real world of three early arthritis clinics, early referral could allow the best outcome, ie, remission, to be reached, and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa. 1795 patients with early arthritis (symptom duration≤12 months) were entered into a prospective follow-up study. 711 patients (39.6%) were diagnosed with rheumatoid arthritis (RA). Each RA patient was treated according to the local algorithm, in three tertiary referral centres (representing a small province, a medium sized province and a metropolitan area, respectively). Remission, defined using the disease activity score in 28 joints (DAS28<2.6) and American College of Rheumatology (ACR) criteria, was the major outcome evaluated at the 12-month follow-up. DAS28 remission was achieved in 34.3% (range 19.5-49%) of RA patients and ACR remission in 15.2% (range 8.5-20.6%). At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome: being in very early rheumatoid arthritis (VERA; less than 12 weeks symptom duration at the time of first treatment) and being on disease-modifying antirheumatic drugs (DMARD) within 3 months from disease onset. Among RA patients in remission, only 10% of VERA subjects received an anti-TNF blocker compared with 32.2% of non-VERA patients (p=0.002, OR 0.23, 95% CI 0.09 to 0.64). In a real-world setting, the 12 weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome, ie, remission of RA. Moreover, VERA represents a window of opportunity in terms of cost saving.

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1⁺ and FCN1⁺SPP1⁺ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48^hiS100A12⁺ and CD48⁺SPP1⁺ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4⁺ predominant in healthy lung was transcriptionally related to STM cluster TREM2⁺ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post–COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1⁺ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14⁺ monocytes and development of PD-L1⁺ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post–COVID-19 pathology.