Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression

Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. Objective: To determine ex vivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel. Methods: We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Results: Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS (p = 0.04). Conclusion: Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra

Comment on ‘Cutaneous manifestations in COVID‐19: a first perspective’ by Recalcati S

International audienceSince the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2), patients with COVID‐19 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled “Cutaneous manifestations in COVID‐19: a first perspective ” by Recalcati S. (5)