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

Objective Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are associated with statin exposure, the HLA allele DRB1*11:01, and necrotizing muscle biopsies in adult myositis patients. The aim of this study was to characterize the features of pediatric anti-HMGCR-positive myositis patients. Methods The sera of 440 juvenile myositis patients were screened for anti-HMGCR autoantibodies. Demographic and clinical features, responses to therapy, and HLA alleles were assessed. The features of anti-HMGCR-positive patients were compared to those of previously described adult patients with this autoantibody and to children with other myositis-specific autoantibodies (MSAs). Results Five (1.1%) of 440 patients were anti-HMGCR-positive; none had taken statin medications. Three patients had rashes characteristic of juvenile dermatomyositis and two patients had immune-mediated necrotizing myopathies. The median highest creatine kinase (CK) level of anti-HMGCR-positive subjects was 17,000 IU/L. All patients had severe proximal muscle weakness, distal weakness, muscle atrophy, joint contractures, and arthralgias, which were all more prevalent in HMGCR-positive subjects compared to MSA-negative patients or those with other MSAs. Anti-HMGCR-positive patients had only partial responses to multiple immunosuppressive medications and often a chronic course. The DRB1*07:01allele was present in all 5 patients compared to 26.25% of healthy controls (Pcorrected=0.01); none of the 5 pediatric patients had DRB1*11:01. Conclusions Compared to children with other MSAs, muscle disease appeared to be more severe in those with anti-HMGCR autoantibodies. Like adults, children with anti-HMGCR autoantibodies have severe weakness and high CK levels. In contrast to adults, anti-HMGCR-positive children have a strong association with HLA DRB1*07:01.

This comprehensive survey of North American pediatric rheumatology providers regarding transitional care practices demonstrates deficiencies in education, resources, and a formalized process. Respondents support development of standardized rheumatology-specific transition practices.

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