PReS-FINAL-2324: PAPA syndrome clinical spectrum and IL-1Β release

Results Monocytes isolated from PAPA patients tent to secrete higher levels of IL-1b but this was not consistent in all the patients (p = 0.144). Variability in IL-1b release occurred even in the presence of the same PSTPIP1 variant and it did not parallel disease activity when the whole cohort was taken in consideration. However, IL-1b levels varied according to the clinical picture (p = 0.0197), and it was significantly higher (P < 0.05) in patients displaying articular manifestations (N = 3) compared to those affected by cutaneous (N =6 ) or combined (N = 2) lesions. In the former, IL-1b secretion was increased in the presence of acute phase reactants elevation and active joint lesions, and treatment with Anakinra resulted in acute phase reactans normalization and symptom-free period. Silencing of of NLRP3 activity consistently inhibited LPS-induced IL-1b release in both PAPA and HD monocytes. Conclusion IL-1b secretion is higher in PAPA patients displaying prevalent articular manifestations. In these patients, IL-1b release correlates with disease activity and it is mediated by NLRP3.