Disease activity accounts for long-term efficacy of IL-1 blockers in pyogenic sterile arthritis pyoderma gangrenosum and severe acne syndrome

Alessia Omenetti, Sonia Carta, Roberta Caorsi, Martina Finetti, Daniela Marotto, Bianca Lattanzi, Mauro Jorini, Laura Delfino, Federica Penco, Paolo Picco, Antonella Buoncompagni, Alberto Martini, Anna Rubartelli, Marco Gattorno

Research output: Contribution to journalArticlepeer-review


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-a 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.

Original languageEnglish
Article numberkew031
Pages (from-to)1325-1335
Number of pages11
Issue number7
Publication statusPublished - Jul 1 2016


  • Anti-IL-1 monoclonal antibody
  • IL-1
  • IL-1 receptor antagonist
  • NLRP3 inflammasome
  • PAPA syndrome

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)


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