{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:46:18Z","timestamp":1789706778491,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T00:00:00Z","timestamp":1480636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007820","name":"Alliance for Lupus Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007820","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Mutations in the <jats:italic>ACP5<\/jats:italic> gene, which encodes tartrate\u2010resistant acid phosphatase (TRAP), cause the immuno\u2010osseous disorder spondyloenchondrodysplasia, which includes as disease features systemic lupus erythematosus (SLE) and a type I interferon (IFN) signature. Our aims were to identify TRAP substrates, determine the consequences of TRAP deficiency in immune cells, and assess whether <jats:italic>ACP5<\/jats:italic> mutations are enriched in sporadic cases of SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Interaction between TRAP and its binding partners was tested by a yeast 2\u2010hybrid screening, confocal microscopy, and immunoprecipitation\/Western blotting. TRAP knockdown was performed using small interfering RNA. Phosphorylation of osteopontin (OPN) was analyzed by mass spectrometry. Nucleotide sequence analysis of <jats:italic>ACP5<\/jats:italic> was performed by Sanger sequencing or next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TRAP and OPN colocalized and interacted in human macrophages and plasmacytoid dendritic cells (PDCs). TRAP dephosphorylated 3 serine residues on specific OPN peptides. TRAP knockdown resulted in increased OPN phosphorylation and increased nuclear translocation of <jats:italic>IRF7<\/jats:italic> and <jats:italic>P65<\/jats:italic>, with resultant heightened expression of IFN\u2010stimulated genes and <jats:italic>IL6<\/jats:italic> and <jats:italic>TNF<\/jats:italic> following Toll\u2010like receptor 9 stimulation. An excess of heterozygous <jats:italic>ACP5<\/jats:italic> missense variants was observed in SLE compared to controls (<jats:italic>P<\/jats:italic>\u2009=\u20090.04), and transfection experiments revealed a significant reduction in TRAP activity in a number of variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that TRAP and OPN colocalize and that OPN is a substrate for TRAP in human immune cells. TRAP deficiency in PDCs leads to increased IFN\u03b1 production, providing at least a partial explanation for how <jats:italic>ACP5<\/jats:italic> mutations cause lupus in the context of spondyloenchondrodysplasia. Detection of <jats:italic>ACP5<\/jats:italic> missense variants in a lupus cohort suggests that impaired TRAP functioning may increase susceptibility to sporadic lupus.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39810","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T11:26:28Z","timestamp":1467890788000},"page":"131-142","source":"Crossref","is-referenced-by-count":61,"title":["Tartrate\u2010Resistant Acid Phosphatase Deficiency in the Predisposition to Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"69","author":[{"given":"Jie","family":"An","sequence":"first","affiliation":[{"name":"University of Washington Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Briggs","sequence":"additional","affiliation":[{"name":"University of Manchester and St. Mary's Hospital, Central Manchester Foundation Trust Manchester 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