{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:30:28Z","timestamp":1786977028598,"version":"build-2736575974"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Dominantly inherited\n                      <jats:italic>PSTPIP1<\/jats:italic>\n                      mutations cause a spectrum of autoinflammatory manifestations epitomized by PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome.). The connections between\n                      <jats:italic>PSTPIP1<\/jats:italic>\n                      and PAPA syndrome are poorly understood, although evidence suggests involvement of pyrin inflammasome activation. Interleukin\u201018 (IL\u201018) is an inflammasome\u2010activated cytokine associated with susceptibility to macrophage activation syndrome (MAS). This study was undertaken to investigate an association of IL\u201018 with PAPA syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical and genetic data and serum samples were obtained from patients referred to institutions due to symptoms indicative of PAPA syndrome. Serum IL\u201018, IL\u201018 binding protein (IL\u201018BP), and CXCL9 levels were assessed by bead\u2010based assay, and free IL\u201018 levels were assessed by enzyme\u2010linked immunosorbent assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The symptoms of\n                      <jats:italic>PSTPIP1<\/jats:italic>\n                      \u2010positive patients with PAPA syndrome overlapped with those of mutation\u2010negative patients with PAPA\u2010like conditions, but mutation\u2010positive patients had earlier onset and a greater proportion had a history of arthritis. We found uniform elevation of total serum IL\u201018 in treated PAPA syndrome patients at levels nearly as high as those seen in NLRC4\u2010associated autoinflammation with infantile enterocolitis patients, and well above levels found in most familial Mediterranean fever patients. Serum IL\u201018 elevation in PAPA syndrome patients persisted despite fluctuations in disease activity. Levels of the soluble IL\u201018 antagonist IL\u201018BP were modestly elevated, and PAPA syndrome patients had detectable free IL\u201018. PAPA syndrome was rarely associated with elevation of CXCL9, an indicator of interferon\u2010\u03b3 activity, but no PAPA syndrome patients had a history of MAS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PAPA syndrome is a refractory and often disabling monogenic autoinflammatory disease associated with chronic and unopposed elevation of serum IL\u201018 levels but not with risk of MAS. These findings affect our understanding of the diseases in which IL\u201018 is overproduced and suggest a link between pyrin inflammasome activation, IL\u201018, and autoinflammation, without susceptibility to MAS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41976","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T14:33:48Z","timestamp":1631025228000},"page":"353-357","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Excess Serum Interleukin\u201018 Distinguishes Patients With Pathogenic Mutations in\n                    <scp>\n                      <i>PSTPIP1<\/i>\n                    <\/scp>"],"prefix":"10.1002","volume":"74","author":[{"given":"Deborah L.","family":"Stone","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Ombrello","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4757-504X","authenticated-orcid":false,"given":"Juan I.","family":"Arostegui","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednic de Barcelona, Institut d'Investigacions Biom\u00e9diques August Pi i Sunyer  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Schneider","sequence":"additional","affiliation":[{"name":"University of Pittsburgh and UPMC Children's Hospital of Pittsburgh  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinh","family":"Dang","sequence":"additional","affiliation":[{"name":"University of Pittsburgh and UPMC Children's Hospital of Pittsburgh  Pittsburgh Pennsylvania"},{"name":"The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"de Jesus","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Girard\u2010Guyonvarc'h","sequence":"additional","affiliation":[{"name":"University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem","family":"Gabay","sequence":"additional","affiliation":[{"name":"University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4412-8519","authenticated-orcid":false,"given":"Wonyong","family":"Lee","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Jin","family":"Chae","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Aksentijevich","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphaela T.","family":"Goldbach\u2010Mansky","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Kastner","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH  Bethesda 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