Disease activity accounts for long-term efficacy of IL-1 blockers in pyogenic sterile arthritis pyoderma gangrenosum and severe acne syndrome.
Objective. To provide a rationale for anti-IL-1 treatment in pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) by defining whether IL-1β secretion is enhanced; requires NLRP3; and correlates with proline-serine-threonine phosphatase-interacting protein 1 mutations, disease activity an...
| Publicado en: | Rheumatology Vol. 55; no. 7; pp. 1325 - 1336 |
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| Autores principales: | , , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Jul2016
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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=116280645&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 116280645 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14620324 DN9 jtl: Rheumatology issn: 14620324 maglogo: N pubinfo: dt: Jul2016 vid: 55 iid: 7 pid: 622 pub: Oxford University Press / USA artinfo: ui: 116280645 116280645 116280645 10.1093/rheumatology/kew031 116280645 ppf: 1325 ppct: 11 formats: tig: atl: Disease activity accounts for long-term efficacy of IL-1 blockers in pyogenic sterile arthritis pyoderma gangrenosum and severe acne syndrome. aug: au: Omenetti, Alessia Carta, Sonia Caorsi, Roberta Finetti, Martina Marotto, Daniela Lattanzi, Bianca Jorini, Mauro Delfino, Laura Penco, Federica Picco, Paolo Buoncompagni, Antonella Martini, Alberto Rubartelli, Anna Gattorno, Marco affil: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal-Infant Sciences (DINOGMI), University of Genoa, Italy sug: subj: Pyoderma Gangrenosum Arthritis Acne Vulgaris Hereditary Autoinflammatory Diseases Drug Therapy Interleukin 1 Immunology Interleukin 1 Antagonists and Inhibitors Mutation Human Descriptive Statistics Enzyme-Linked Immunosorbent Assay Sequence Analysis Retrospective Design Pedigree Polymerase Chain Reaction Cytokines Mann-Whitney U Test Kruskal-Wallis Test Post Hoc Analysis Funding Source ab: Objective. To provide a rationale for anti-IL-1 treatment in pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) by defining whether IL-1β secretion is enhanced; requires NLRP3; and correlates with proline-serine-threonine phosphatase-interacting protein 1 mutations, disease activity and/or the clinical picture in PAPA. Methods. Monocytes were isolated from 13 patients and 35 healthy donors and studied at baseline and following activation. Secretion pattern of IL-1β, IL-1α, IL-1Ra, IL-6, IL-18 and TNF-α was assessed in supernatants by ELISA. The NLRP3 requirement for IL-1β secretion was investigated by silencing technique in PAPA and healthy donor monocytes. Long-term follow-up (mean 26 months, range 4-38) was performed in five patients enrolled in an anti-IL-1 regimen. Results. IL-1β secretion in PAPA is increased, requires NLRP3 and correlates with disease activity. Patients with a history of osteoarticular flares release more IL-1β, IL-6 and TNF-α compared with those with predominant cutaneous recurrences. Monocytes from patients in anti-IL-1 treatment dramatically reduced IL-1β secretion after ex vivo activation, and long-term follow-up demonstrated decreased frequency of flares and normalization of acute phase reactants in all the patients. A straightforward correlation between genotype and IL-1β signalling was not observed suggesting that factors other than mutation itself may play a role in regulating IL-1β secretion and response to treatment in PAPA. Conclusion. PAPA patients with active lesions display increased NLRP3-mediated IL-1β secretion, and long-term efficacy of IL-1 blockade was demonstrated. Even if other mechanisms related to the complex proline-serine-threonine phosphatase-interacting protein 1 protein networking might play additional roles, this study further supports the potential of IL-1 blockade as an effective therapeutic strategy in PAPA syndrome. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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