{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:06:13Z","timestamp":1783933573387,"version":"3.55.0"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To verify the pathogenesis of the opioid growth factor receptor like\u20101 (\n                      <jats:italic>OGFRL1)<\/jats:italic>\n                      loss\u2010of\u2010function variant (c.30del, p. F10Ffs*110) identified in a patient with chronic recurrent multifocal osteomyelitis (CRMO) and to investigate the underlying mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole exome sequencing and Sanger sequencing were performed to identify and confirm the variant. Quantitative polymerase chain reaction, enzyme\u2010linked immunosorbent assay, cytometric bead assay, bulk RNA sequencing, and single\u2010cell RNA sequencing were conducted to detect the inflammatory signatures of the patient versus healthy controls. A collagen antibody\u2013induced arthritis (CAIA) model was generated in\n                      <jats:italic>Ogfrl1<\/jats:italic>\n                      knockout (KO) and wild type (WT) mice, and micro\u2013computed tomography scan was performed to investigate the pathogenicity of\n                      <jats:italic>Ogfrl1<\/jats:italic>\n                      deficiency. In addition, osteoclast induction and differentiation in vitro was exerted to explore the underlying mechanism of\n                      <jats:italic>Ogfrl1<\/jats:italic>\n                      deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patient exhibited up\u2010regulated mitogen\u2010activated protein kinase (MAPK) and NF\u2010\u03baB signaling pathways, along with overproduction of pro\u2010inflammatory cytokines. Compared to healthy controls, apparent activation of myeloid cells was observed, especially in monocytes, dendritic cells, and low\u2010density granulocytes (LDGs) of the patient. In the CAIA model,\n                      <jats:italic>Ogfrl1<\/jats:italic>\n                      KO mice developed more severe and persistent arthritis and bone erosion than WT mice.\n                      <jats:italic>Ogfrl1<\/jats:italic>\n                      KO mice were more prone to osteoclast differentiation than WT mice. The patient responded well to tumor necrosis factor inhibitor therapy, with normalization of C\u2010reactive protein levels, erythrocyte sedimentation rate, serum amyloid A levels, and interleukin\u20106 levels, as well as improvement in osteolytic lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identified OGFRL1 deficiency as a novel cause of CRMO, highlighted the previously unrecognized role of\n                      <jats:italic>OGFRL1<\/jats:italic>\n                      in restraining inflammatory responses, and provided novel insights into the pathogenesis and treatment of this autoinflammatory disorder.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70057","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T11:04:03Z","timestamp":1769079843000},"page":"1318-1326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>OGFRL1<\/scp>\n                    Deficiency Causes Chronic Recurrent Multifocal Osteomyelitis Via Pathologic Osteoclastogenesis, With Therapeutic Response to Tumor Necrosis Factor Inhibitor"],"prefix":"10.1002","volume":"78","author":[{"given":"Wen","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Shenzhen Children's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusha","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sir Run Run Shaw Hospital Zhejiang University School of Medicine, and Liangzhu Laboratory of Zhejiang University  Hangzhou 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