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She had a 17.8\u2010kb deletion on the maternal\n                      <jats:italic>LPIN2<\/jats:italic>\n                      allele and a splice site mutation, p.R517H, that variably spliced out exons 10 and 11 on the paternal\n                      <jats:italic>LPIN2<\/jats:italic>\n                      allele. The patient achieved long\u2010lasting remission receiving IL\u20101 blockade with canakinumab. Compared to controls, monocytes and monocyte\u2010derived M1\u2010like macrophages from the patient with Majeed syndrome and those with NOMID or DIRA had elevated caspase 1 activity and IL\u20101\u03b2 secretion. In contrast, lipopolysaccharide\u2010stimulated, monocyte\u2010derived, M2\u2010like macrophages from the patient with Majeed syndrome released higher levels of osteoclastogenic mediators (IL\u20108, IL\u20106, tumor necrosis factor, CCL2, macrophage inflammatory protein 1\u03b1\/\u03b2, CXCL8, and CXCL1) compared to NOMID patients and healthy controls. Accelerated osteoclastogenesis in the patient with Majeed syndrome was associated with higher NFATc1 levels, enhanced JNK\/MAPK, and reduced Src kinase activation, and partially responded to JNK inhibition and IL\u20101 (but not IL\u20106) blockade.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We report 2 novel compound heterozygous disease\u2010causing mutations in\n                      <jats:italic>LPIN2<\/jats:italic>\n                      in an American patient with Majeed syndrome.\n                      <jats:italic>LPIN2<\/jats:italic>\n                      deficiency drives differentiation of proinflammatory M2\u2010like macrophages and enhances intrinsic osteoclastogenesis. This provides a model for the pathogenesis of sterile osteomyelitis which differentiates Majeed syndrome from other IL\u20101\u2013mediated autoinflammatory diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41624","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T10:05:33Z","timestamp":1607940333000},"page":"1021-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Novel Majeed Syndrome\u2013Causing\n                    <i>LPIN2<\/i>\n                    Mutations Link Bone Inflammation to Inflammatory M2 Macrophages and Accelerated Osteoclastogenesis"],"prefix":"10.1002","volume":"73","author":[{"given":"Farzana","family":"Bhuyan","sequence":"first","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana 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