onset in infancy (SAVI), and another by additive loss-of-function mutations in proteasome genes causing the proteasome-associated autoinflammatory syndromes (PRAAS) (also, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures [CANDLE]), presented with chronically elevated interferon (IFN) signatures, suggesting a pathogenic role for type-I IFN in autoinflammatory diseases (2, 3). Type-I IFN was first discovered as a soluble antiviral factor over 50 years ago, and a role in sterile inflammation was proposed in patients with systemic lupus erythematosus (4). However, the discovery of genetic mutations that cause the autoinflammatory type-I interferonopathies CANDLE (2, 5), SAVI (3, 6-8), and Aicardi-Goutières syndrome (AGS) (9, 10) have shed light on pathomechanisms that drive chronic IFN signaling, and recent studies blocking IFN signaling validate a critical role for type-I IFNs (11). AGS-causing loss-of-function mutations in nucleases impair self-nucleic acid homeostasis, SAVI-causing

After a period of major improvement, survival in SLE has plateaued since the mid-1990s. In high-income countries, 5-year survival exceeds 0.95 in both adults and children. In low/middle-income countries, 5-year and 10-year survival was lower among children than adults.

The nucleolus is the site of ribosome biosynthesis, but is now known to have other functions as well. In the present study we have investigated how the distribution of signal recognition particle (SRP) RNA within the nucleolus relates to the known sites of ribosomal RNA synthesis, processing, and nascent ribosome assembly (i.e., the fibrillar centers, the dense fibrillar component (DFC), and the granular component). Very little SRP RNA was detected in fibrillar centers or the DFC of the nucleolus, as defined by the RNA polymerase I–specific upstream binding factor and the protein fibrillarin, respectively. Some SRP RNA was present in the granular component, as marked by the protein B23, indicating a possible interaction with ribosomal subunits at a later stage of maturation. However, a substantial portion of SRP RNA was also detected in regions of the nucleolus where neither B23, UBF, or fibrillarin were concentrated. Dual probe in situ hybridization experiments confirmed that a significant fraction of nucleolar SRP RNA was not spatially coincident with 28S ribosomal RNA. These results demonstrate that SRP RNA concentrates in an intranucleolar location other than the classical stations of ribosome biosynthesis, suggesting that there may be nucleolar regions that are specialized for other functions.

Purpose of Review Atherosclerotic cardiovascular disease confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE) and cannot be fully explained by traditional cardiovascular risk factors. Recent immunologic discoveries have outlined putative pathways in SLE that may also accelerate the development of atherosclerosis. Recent findings Aberrant innate and adaptive immune responses implicated in lupus pathogenesis may also contribute to the development of accelerated atherosclerosis in these patients. Defective apoptosis, abnormal lipoprotein function, autoantibodies, aberrant neutrophil responses and a dysregulated type I interferon pathway likely contribute to endothelial dysfunction. SLE macrophages have an inflammatory phenotype that may drive progression of plaque. Summary Recent discoveries have placed increase emphasis on the immunology of atherosclerotic cardiovascular disease. Understanding the factors that drive the increase risk for CVD in SLE patients may provide selective therapeutic targets for reducing inflammation and improving outcomes in atherosclerosis.

Background The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide.Methods Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. Findings 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46•1 years; 8375 [90•1%] women, 893 [9•6%] men, and 32 [0•3%] participants who identified as non-binary). 6273 (67•5%) of respondents identified as White, 1565 (16•8%) as Latin American, 198 (2•1%) as Black, 190 (2•0%) as Asian, and 42 (0•5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39•1%] of 9300), systemic lupus erythematosus (2882 [31•0%]), and Sjögren's syndrome (1290 [13•9%]). Most respondents (6921 [82•0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99•7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27•1%) of 9300) of respondents, with a 13•6% decrease in the number in full-time employment (from 4066 to 3514).Interpretation People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity.Funding American College of Rheumatology.

Background Systemic Lupus Erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE (pSLE) on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa (SA). Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serologic characteristics was extracted from medical records. Results were compared to a well-described North American pSLE cohort. Results Seventy-two SA patients were enrolled in the study; mean age 11.5 years, 82% female. The racial distribution was 68% Coloured, 24% Black, 5% White, and 3% Asian/Indian. Most patients presented with severe lupus nephritis (LN) documented by renal biopsy (61%). Of patients with LN, 63% presented with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate, and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K [SLEDAI-2K] 20.6). The SLEDAI-2K at enrollment in the PULSE cohort (5.0) did not differ from the North American pSLE cohort (4.8). Sixty three % of PULSE cohort had end organ damage with System Lupus International Collaborating Clinic-Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, 9 (13%) developed ESRD with 6 (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrollment in the SA registry. SA patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study reveals a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

No abstract

Purpose of the review To highlight the current challenges in diagnosis and clinical care of pediatric rheumatic disease and barriers to research and education of pediatric rheumatologists worldwide. Recent findings Recent studies and reports demonstrate a paucity of studies on epidemiology, outcomes, and management guidelines from many regions of the world. There have been noteworthy efforts to bridge the gap in under resourced areas. An analysis of the global burden of rheumatic disease has demonstrated that while understudied, musculoskeletal diseases are prevalent and increasingly contribute to loss of years of healthy life. In juvenile idiopathic arthritis, two milestone publications in global pediatric rheumatology have recently been published. An international study evaluated the epidemiology, treatment, and outcomes of juvenile idiopathic arthritis and demonstrated global diversity in both clinical manifestations and outcomes. Notably, the first guidelines for managing pediatric rheumatic disease in a less resourced setting have been published for juvenile idiopathic arthritis. This document offers the first publication targeted to address challenges faced by pediatric rheumatology caregivers in low-resourced settings. These documents serve as exemplars for international collaboration in pediatric rheumatology and can be used as models for other pediatric rheumatic disease research. Other efforts are making progress in various arenas towards increasing access to care, education, and training in pediatric rheumatology. Summary The global burden of rheumatic disease in the pediatric population is poorly understood but unrecognized disease greatly impacts the overall morbidity and mortality in this population. More studies in lesser resourced regions are needed to prioritize access to pediatric rheumatology care and prioritize a further increase in research capacity and education moving forward.