Psoriasis is a chronic inflammatory disease of the skin with autoimmune background. 1 The worldwide prevalence is estimated to be 2-4%, rising up to 9.7% in Scandinavian countries. 2,3 A number of studies have highlighted the fundamental role of the genetic background, the immune system and the environment in the pathogenesis of psoriasis. 4-6 The most common clinical variant of the disease is psoriasis vulgaris (plaque psoriasis), which accounts for approximately

Psoriasis is a chronic inflammatory disease of the skin, with clinically characteristic erythematous and thick scaling plaques. 1 It is now well acknowledged that in addition to psoriatic arthritis (PsA), other comorbidities such as metabolic syndrome, cardiovascular diseases, gastrointestinal diseases, psychosocial disorders, infections and malignancies may accompany psoriasis. 2 They appear to result from environmental (e.g., infection or skin trauma) and genetic factors as well as enhanced levels of various inflammatory mediators, in particular circulating lymphocytes and other peripheral blood mononuclear cells, transcription factors and cytokines like tumour necrosis factor (TNF), interleukin (IL)-12/IL-23 and IL-17. 3-5 Multiple susceptibility loci associated with innate and adaptive components of the immune system together with skin resident cell types are involved in the complex inflammatory network that drives psoriatic disease. 6 The most predominant susceptibility allele for psoriasis, the human leucocyte antigen (HLA) susceptibility locus HLA-C*06:02, is strongly associated with early onset and more severe disease. 1 To date, it has been agreed that psoriasis is

BackgroundPrimary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, characterized by mononuclear cell infiltrates in the salivary and lacrimal glands, leading to glandular atrophy and dryness. Patient heterogeneity and lack of knowledge regarding its pathogenesis makes pSS a difficult disease to manage.MethodsAn exploratory analysis using mass cytometry was conducted of MAPK/ERK and JAK/STAT signaling pathways in peripheral blood mononuclear cells (PBMC) from 16 female medication free pSS patients (8 anti-Sjögren’s syndrome-related antigen A negative/SSA- and 8 SSA+) and 8 female age-matched healthy donors after stimulation with interferons (IFNs).ResultsWe found significant differences in the frequencies of memory B cells, CD8+ T central and effector memory cells and terminally differentiated CD4+ T cells among the healthy donors and patient subgroups. In addition, we observed an upregulation of HLA-DR and CD38 in many cell subsets in the patients. Upon IFNα2b stimulation, slightly increased signaling through pSTAT1 Y701 was observed in most cell types in pSS patients compared to controls, while phosphorylation of STAT3 Y705 and STAT5 Y694 were slightly reduced. IFNγ stimulation resulted in significantly increased pSTAT1 Y701 induction in conventional dendritic cells (cDCs) and classical and non-classical monocytes in the patients. Most of the observed differences were more prominent in the SSA+ subgroup, indicating greater disease severity in them.ConclusionsAugmented activation status of certain cell types along with potentiated pSTAT1 Y701 signaling and reduced pSTAT3 Y705 and pSTAT5 Y694 induction may predispose pSS patients, especially the SSA+ subgroup, to upregulated expression of IFN-induced genes and production of autoantibodies. These patients may benefit from therapies targeting these pathways.

Patients with psoriasis on infliximab have higher activation levels of PBMCs than do healthy controls, possibly reflecting systemic inflammation. Switching from the originator infliximab to biosimilar CT-P13 did not affect phosphorylation levels or clinical parameters, suggesting that CT-P13 is a noninferior treatment alternative to the originator infliximab.

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.