Excess Serum Interleukin‐18 Distinguishes Patients With Pathogenic Mutations in PSTPIP1.
Objective: Dominantly inherited PSTPIP1 mutations cause a spectrum of autoinflammatory manifestations epitomized by PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome.). The connections between PSTPIP1 and PAPA syndrome are poorly understood, although evidence...
| Publicado en: | Arthritis & Rheumatology Vol. 74; no. 2; pp. 353 - 358 |
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| Autores principales: | , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Feb2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=154961147&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 154961147 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23265191 H06R jtl: Arthritis & Rheumatology issn: 23265191 maglogo: N pubinfo: dt: Feb2022 vid: 74 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 154961147 154449653 154961147 154961147 10.1002/art.41976 154961147 ppf: 353 ppct: 5 formats: tig: atl: Excess Serum Interleukin‐18 Distinguishes Patients With Pathogenic Mutations in PSTPIP1. aug: au: Stone, Deborah L. Ombrello, Amanda Arostegui, Juan I. Schneider, Corinne Dang, Vinh de Jesus, Adriana Girard‐Guyonvarc'h, Charlotte Gabay, Cem Lee, Wonyong Chae, Jae Jin Aksentijevich, Ivona Goldbach‐Mansky, Raphaela T. Kastner, Daniel L. Canna, Scott W. affil: National Human Genome Research Institute, NIH, Bethesda Maryland sug: subj: Interleukins Blood Mutation Pyoderma Gangrenosum Physiopathology Acne Vulgaris Physiopathology Arthritis, Infectious Physiopathology Human Chemokines Blood Enzyme-Linked Immunosorbent Assay Severity of Illness Descriptive Statistics Pyoderma Gangrenosum Symptoms Arthritis, Infectious Symptoms Acne Vulgaris Symptoms Child Adolescence Adult Middle Age Pyoderma Gangrenosum Diagnosis Acne Vulgaris Diagnosis Arthritis, Infectious Diagnosis Biological Markers Blood Female Male Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: Objective: Dominantly inherited PSTPIP1 mutations cause a spectrum of autoinflammatory manifestations epitomized by PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome.). The connections between PSTPIP1 and PAPA syndrome are poorly understood, although evidence suggests involvement of pyrin inflammasome activation. Interleukin‐18 (IL‐18) is an inflammasome‐activated cytokine associated with susceptibility to macrophage activation syndrome (MAS). This study was undertaken to investigate an association of IL‐18 with PAPA syndrome. Methods: Clinical and genetic data and serum samples were obtained from patients referred to institutions due to symptoms indicative of PAPA syndrome. Serum IL‐18, IL‐18 binding protein (IL‐18BP), and CXCL9 levels were assessed by bead‐based assay, and free IL‐18 levels were assessed by enzyme‐linked immunosorbent assay. Results: The symptoms of PSTPIP1‐positive patients with PAPA syndrome overlapped with those of mutation‐negative patients with PAPA‐like conditions, but mutation‐positive patients had earlier onset and a greater proportion had a history of arthritis. We found uniform elevation of total serum IL‐18 in treated PAPA syndrome patients at levels nearly as high as those seen in NLRC4‐associated autoinflammation with infantile enterocolitis patients, and well above levels found in most familial Mediterranean fever patients. Serum IL‐18 elevation in PAPA syndrome patients persisted despite fluctuations in disease activity. Levels of the soluble IL‐18 antagonist IL‐18BP were modestly elevated, and PAPA syndrome patients had detectable free IL‐18. PAPA syndrome was rarely associated with elevation of CXCL9, an indicator of interferon‐γ activity, but no PAPA syndrome patients had a history of MAS. Conclusion: PAPA syndrome is a refractory and often disabling monogenic autoinflammatory disease associated with chronic and unopposed elevation of serum IL‐18 levels but not with risk of MAS. These findings affect our understanding of the diseases in which IL‐18 is overproduced and suggest a link between pyrin inflammasome activation, IL‐18, and autoinflammation, without susceptibility to MAS. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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