Anales RANF

P.80 INVESTIGATION ON THE ROLE OF THE P2X7R-NLRP3-IL-1 β AXIS IN THE PATHOGENESIS OF HIDRADENITIS SUPPURATIVA A.L. Giuliani 1 , M. Manfredini 2 , E. Zoppas 1 , V. Roveri 1 , S. Alessio 1 , A. Spina 1 , A. Amico 1 , V. Bettoli 3 , F. Di Virgilio 1 1 University of Ferrara, 2 University of Modena and Reggio Emilia, 3 AOU S. Anna of Ferrara, Italy. Hidradenitis Suppurativa (HS) is a chronic cutaneous inflammatory pathology of the terminal hair follicle characterised by painful, inflamed, deep lesions in the axillae, groin and anogenital region. HS pathogenesis is multifactorial involving genetic, hormonal, immunological, microbial, environmental and dietary factors. In HS lesional skin, the NLRP3-inflammasome inflammatory pathway has been found over-expressed [1]. Until now, no research has been dedicated to explore in HS the role of the pro- inflammatory P2X7R, the main activator of the NLRP3 inflammasome and IL- 1β production [2]. The aim of this study was to evaluate whether P2X7R is involved in HS pathogenesis. For this, thirty HS patients and thirty healthy control (HC) subjects were studied. Immuno-histochemical (IHC) analysis of skin samples was performed using anti- P2X7R, anti-NLRP3 and anti-IL-1 β antibodies. Ficoll gradient isolated peripheral blood mononuclear cells (PBMCs) were used to detect Benzoyl-ATP (BzATP)-stimulated IL- 1β secretion following lipopolysaccharide (LPS) incubation. IL - 1β in plasma and PBMCs supernatants was measured using the human IL- 1β/IL -1F2 Quantikine ELISA kit (R&D System). P2X7R IHC staining scored from 2+ to 4+ in lesional skin of 21 out of 30 HS patients, whereas it ranged from - to 2+ in HC subjects (p <0.001). A variable degree of positivity was detected in the dermis, especially in the inflammatory infiltrate, of HS patients. NLRP3 and IL-1 β staining was analogously higher in HS than in HC skin samples (p <0.001). IL- 1β plasma levels were more elevated in HS patients than in HC subjects (p = 0.02). Unexpectedly, BzATP-stimulated PBMCs of HS patients released lower levels of IL- 1β than PBMCs of HC subjects (p <0.05). Our data indicate P2X7R-NLRP3- IL- 1β axis involvement in the pathogenesis of HS. Respect to HC subjects, HS patients showed higher P2X7R expression in the lesional skin and higher plasma IL- 1β levels. Since, as found elsewhere [3], PBMCs of HS patients appeared either inhibited or exhausted in IL-1 β release, a role for P2X7R- NLRP3 inflammasome in boosting IL-1 β production at HS skin level is suggested. These results open new perspectives in finding novel efficacious therapies for HS.