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Anti\u2010Sp4 autoantibodies co\u2010occurred in patients with anti\u2013transcription intermediary factor 1 (anti\u2010TIF1) autoantibody\u2010positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti\u2010Sp4 autoantibodies in juvenile\u2010onset IIM were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum samples from 336 patients with juvenile myositis in a cross\u2010sectional cohort and 91 healthy controls were screened for anti\u2010Sp4 autoantibodies using enzyme\u2010linked immunosorbent assay. Clinical characteristics, outcomes, and HLA alleles of those with and those without anti\u2010Sp4 autoantibodies were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Anti\u2010Sp4 autoantibodies were present in 23 patients (7%) with juvenile myositis and were not present in any of the controls. Anti\u2010Sp4 autoantibodies were found among each clinical myositis subgroup. The frequency of TIF1 autoantibody positivity was significantly higher among those with anti\u2010Sp4 autoantibodies (21 [91%] versus 92 [30%], <jats:italic>P<\/jats:italic> &lt;\u20090.001). In the anti\u2010TIF1 autoantibody\u2013positive subgroup, Raynaud's phenomenon (8 [38%] versus 2 [2%], <jats:italic>P<\/jats:italic> &lt;\u20090.001) was more common and peak aspartate aminotransferase was significantly lower in those with anti\u2010Sp4 autoantibodies. None of the patients with anti\u2010Sp4 autoantibodies required a wheelchair. Among White patients, DQA1*04 and DRB1*08 were associated with anti\u2010Sp4 autoantibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Anti\u2010Sp4 autoantibodies were found in patients with juvenile\u2010onset IIM, predominantly those with coexisting anti\u2010TIF1 autoantibodies. Patients with anti\u2010Sp4 autoantibodies represent a phenotypic subset of anti\u2010TIF1 autoantibody\u2013positive myositis characterized by frequent Raynaud's phenomenon and less pronounced muscle involvement, similar to adults with these autoantibodies. Novel immunogenetic risk factors for White patients with IIM were identified among juveniles with anti\u2010Sp4 autoantibodies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42512","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T14:14:45Z","timestamp":1680185685000},"page":"1668-1677","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Autoantibodies Recognizing Specificity Protein 4 <scp>Co\u2010occur<\/scp> With Anti\u2013Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5448-1538","authenticated-orcid":false,"given":"Matthew A.","family":"Sherman","sequence":"first","affiliation":[{"name":"Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Pak","sequence":"additional","affiliation":[{"name":"Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6338-9218","authenticated-orcid":false,"given":"Iago","family":"Pinal\u2010Fernandez","sequence":"additional","affiliation":[{"name":"Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, and Department of Neurology Johns Hopkins University School of Medicine  Baltimore 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