Dear Editor, Anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM is associated with life-threatening rapidly progressive interstitial lung disease (RP-ILD). Even after combination immunosuppressive therapy with high-dose glucocorticoid, CYC and calcineurin inhibitors, more than half of patients died within 3 months of disease onset [ 1, 2]. It has been reported that the serum levels of ferritin, IL-6, IL-8 and IL-10 were higher in the RP-ILD subset than in the non-ILD subset or in the chronic ILD subset [ 3]. Treatment targeting B cells and pro-inflammatory cytokines, such as rituximab, tofacitinib, anakinra or plasmapheresis, has shown promising effectiveness [ 4, 5...

Systemic sclerosis is a disease that has significant clinical heterogeneity. This study aims to determine the causes and risk factors of death in a single center European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) cohort at the Peking Union Medical College Hospital (PUMCH) in China. Patients clinically diagnosed with systemic sclerosis (SSc) between Feb 2009 and Dec 2015 were prospectively recruited from the EUSTAR database and Chinese Rheumatism Data Center (CRDC) of the PUMCH. Baseline and follow-up data were collected. Kaplan-Meier analysis was used to estimate survival, and Cox proportional hazards regression analysis was used to identify factors associated with mortality. A total of 448 patients were included in the cohort, of whom 56.7% had limited cutaneous systemic sclerosis (lcSSc). The average age at diagnosis was 42.8 ± 12.1 years. The prevalence of interstitial lung disease (ILD) was 382/447 (85.5%). Among 402 patients, 348 of them took glucocorticoid during the disease course; 374 patients received immunosuppressors. Across 2167 patient-years, 40 patients died. Of these, 27 deaths were attributable to SSc, with pulmonary arterial hypertension (PAH) being the leading cause of death. The median survival time was 53 months. Survival rates from disease diagnosis were 97.0%, 94.6%, 91.1% and 87.8% at 1, 3, 5 and 10 years, respectively. Independent prognostic factors for mortality were PAH (HR 6.248, 95% CI 2.855, 13.674) and arrhythmia (HR 4.729, 95% CI 1.588, 14.082). Tripterygium wilfordii Hook F (TwHF) (log-rank test 7.851, p 0.005) and methotrexate (MTX) (log-rank test 7.925, p = 0.005) were found in survival analysis to be protective treatments against mortality. Patients who used cyclophosphamide (CTX) during the disease course had poorer prognosis (log-rank test 5.177, p = 0.023). In china, although there is a high prevalence of ILD in patients with SSc (85.5%), most of them have reserved pulmonary function, which means that interstitial lung disease (ILD) is not the most important factor in the death of patients with SSc and also is not a risk factor for poor prognosis. Only ILD with pulmonary dysfunction is associated with poor outcome. The 10-year cumulative rate (87.8%) in patients with SSc in China is slightly lower than the Europe, and pulmonary arterial hypertension (PAH) and arrhythmia at baseline are independent prognostic factors, whereas PAH instead of ILD is the leading cause of death in patients with SSc. Interestingly, the Chinese traditional medicine TwHF, as a protective factor for survival deserves further study.

Thickened synovium with a hypoxic oxygenation status as measured with photoacoustic imaging was associated with fewer Doppler US signals and higher disease activity in study participants with rheum... Background Synovial hypoxia is a hallmark of rheumatoid arthritis (RA). Photoacoustic (PA) imaging, based on the use of laser-generated US, can detect the oxygenation status of tissue in individual...

Neuropsychiatric systemic lupus erythematosus (NPSLE) has a broad spectrum of subtypes with diverse severities and prognoses. Ischemic and inflammatory mechanisms, including autoantibodies and cytokine-mediated pathological processes, are key components of the pathogenesis of NPSLE. Additional brain-intrinsic elements (such as the brain barrier and resident microglia) are also important facilitators of NPSLE. An improving understanding of NPSLE may provide further options for managing this disease. The attenuation of neuropsychiatric disease in mouse models demonstrates the potential for novel targeted therapies. Conventional therapeutic algorithms include symptomatic, anti-thrombotic, and immunosuppressive agents that are only supported by observational cohort studies, therefore performing controlled clinical trials to guide further management is essential and urgent. In this review, we aimed to present the latest pathogenetic mechanisms of NPSLE and discuss the progress in its management.

Background: Anti‐melanoma differentiation‐associated gene 5‐positive dermatomyositis (anti‐MDA5+ DM) is a rare inflammatory autoimmune disorder often complicated by life‐threatening rapidly progressive interstitial lung disease (RP‐ILD). The underlying mechanisms driving immune dysfunction and lung injury, however, remain poorly understood. The study aims to gain insights into the disrupted immune landscape in peripheral and pulmonary compartments of severe anti‐MDA5+ DM and explore potential therapeutic targets.Methods: We employed single‐cell RNA sequencing to examine cellular constituents within five patients’ bronchoalveolar lavage fluid and paired peripheral blood mononuclear cells. Luminex assay and flow cytometry were further applied to validate the results.Results: Our analysis revealed starkly contrasting immune landscapes between the periphery and lungs, with peripheral immune suppression juxtaposed against pulmonary immune hyperactivation. Central to this dysregulation was the monocyte–macrophage lineage. Circulating monocytes exhibited an immunosuppressive phenotype, characterised by diminished cytokine production, reduced MHC II expression, and features resembling myeloid‐derived suppressor cells. These monocytes were recruited to the lungs, where they differentiated into monocyte‐derived alveolar macrophages (Mo‐AMs) with robust proinflammatory and profibrotic activities. Mo‐AMs drove cytokine storms and produced chemokines that amplified inflammatory cell recruitment and lung tissue remodelling. Additionally, peripheral T and NK cells exhibited increased cell death and active migration into the lungs, which may be the cause of lymphopenia.Conclusions: Our study underscores the pivotal role of monocyte–macrophage dynamics in the immunopathogenesis of anti‐MDA5+‐associated RP‐ILD, offering critical insights into compartment‐specific immune dysregulation. These findings suggest potential therapeutic strategies targeting monocyte recruitment and macrophage activation to mitigate disease progression.Key points: Peripheral immune suppression and pulmonary immune hyperactivation characterise the distinct immune landscapes in anti‐MDA5+DM with RP‐ILD. Circulating monocytes transition from an immunosuppressive phenotype in the periphery to proinflammatory and profibrotic Mo‐AMs in the lungs. Chemokines produced by Mo‐AMs drive monocyte and other immune cell recruitment to the lungs, amplifying pulmonary inflammation.