{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:40:46Z","timestamp":1775025646285,"version":"3.50.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n \n Spondyloenchondrodysplasia with immune dysregulation (SPENCD) is a rare autosomal recessive disorder caused by biallelic\n ACP5<\/jats:italic>\n mutations and is characterized by skeletal dysplasia, neurological involvement, and immune dysregulation. According to the latest International Union of Immunological Societies (IUIS) classification, SPENCD is categorized as an inborn error of immunity within the autoinflammatory disorders spectrum; however, targeted therapeutic strategies for immune manifestations remain limited.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a multicenter study including five patients from India and from Chongqing and Tianjin, China. Whole-exome sequencing identified six\n ACP5<\/jats:italic>\n variants across the five patients, including four novel variants. The diagnosis of SPENCD was established based on the genetic findings in combination with characteristic clinical features and radiological manifestations. Three patients received treatment with Janus kinase (JAK) inhibitors. In one representative treated patient (Patient 1), immunological parameters before and after treatment were evaluated using flow cytometry and quantitative PCR.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Four novel\n ACP5<\/jats:italic>\n variants were identified in this cohort. All three patients treated with tofacitinib (a JAK inhibitor) showed variable but overall clinical improvement. In one representative patient, immunological changes were observed after treatment, including a reduction in CD21\n low<\/jats:sup>\n B cells and changes in T helper cell subsets.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study expands the spectrum of\n ACP5<\/jats:italic>\n mutations and provides clinical and immunological observations suggesting JAK inhibitor therapy may be considered for immune dysregulation in patients with SPENCD.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1788476","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:44:04Z","timestamp":1775018644000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Janus kinase inhibitor therapy for the treatment of spondyloenchondrodysplasia with immune dysregulation due to novel ACP5 variants: a multicenter study"],"prefix":"10.3389","volume":"17","author":[{"given":"Huilin","family":"Mu","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Children\u2019s Hospital (Tianjin University Children\u2019s Hospital)","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chongqing University Three Gorges Hospital","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Chen","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Children\u2019s Hospital (Tianjin University Children\u2019s Hospital)","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junfeng","family":"Wu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Rheumatology and Immunology, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Yang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Rheumatology and Immunology, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Tang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Rheumatology and Immunology, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Rheumatology and Immunology, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjun","family":"Jia","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Rheumatology and Immunology, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pratap Kumar","family":"Patra","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, All India Institute of Medical Sciences","place":["Patna, Bihar, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nisar Ahmad","family":"Wani","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology, Government Medical College","place":["Srinagar, Kashmir, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saniya","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Edison Hospital","place":["Mohali, Punjab, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Rheumatology and Immunology, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, 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