Mass cytometry analysis of blood immune cells from psoriasis patients on biological therapy.

Psoriasis is a chronic immune-mediated skin disease accompanied by systemic inflammation and comorbidities. We analyzed peripheral blood mononuclear cells (PBMCs) in the search for immune signatures and biomarkers related to psoriasis severity and treatment effect. Thirty-two patients with psoriasis and 10 matched healthy controls were included. PBMCs were collected before and after initiation of anti-TNF, anti-IL-17 or anti-IL-12/23 treatment and analyzed utilizing 26-parameter mass cytometry. The number of circulating Th17, Th22, Th9, and cytotoxic T cells were increased in severe psoriasis. Intracellular pp38 and pERK in T helper cells were associated with disease severity. Differences between responders and nonresponders regarding cell composition and intracellular signaling were identifiable already at inclusion. Biological treatment induced memory cells, restored inhibitory PD-1 function of T cells, and reduced a potential pro-atherogenic profile in monocytes. In conclusion, these results indicate amelioration of systemic inflammation in psoriasis after biological treatment. Such broad immune profiling may enable prospective stratification of patients regarding future treatment response. Successful early intervention may lead to a healthier trajectory with favorable implications on later comorbidities.

Current knowledge on autoantigens and autoantibodies in psoriasis.

In the past decades, clinical and experimental evidence has demonstrated that psoriasis is an immune-mediated inflammatory disease of the skin that occurs in genetically susceptible individuals. Psoriasis also shows clear autoimmune pathomechanisms, but specific cellular targets for the onset and maintenance of psoriatic lesions were not established until 2014. Since then, four psoriasis autoantigens were discovered, namely cathelicidin LL-37, melanocytic ADAMTSL5, lipid antigen PLA2G4D and keratin 17. Autoreactive T cells against these autoantigens were found in a number of patients with moderate-to-severe plaque psoriasis. Moreover, the discovery of autoantibodies against LL-37 and ADAMTSL5 and their strong association with psoriatic arthritis (PsA) suggest a potential role of these autoantibodies in the pathogenesis of PsA. This review discusses the current studies on psoriatic autoantigens and the associated circulating autoantibodies and their mechanisms involved in the development and maintenance of psoriatic plaques. Recent autoimmune evidence fuelled the discussion on psoriasis as an autoimmune skin disorder and has the potential to develop new treatment strategies with protective and therapeutic antigen-targeted methods.