Immune cell activity during anti-TNF treatment in patients with psoriasis and psoriatic arthritis.

Psoriasis is a chronic, inflammatory skin disease characterized by a dysregulated immune response and systemic inflammation. Up to one-third of patients with psoriasis have psoriatic arthritis (PsA). Targeted treatment with antibodies neutralizing tumor necrosis factor (TNF) can ameliorate both diseases. We here explored the impact of long-term infliximab treatment on the composition and activity status of circulating immune cells involved in chronic skin and joint inflammation. Immune cells were analyzed by multicolor flow cytometry. We measured markers of immune activation in peripheral blood mononuclear cell (PBMC) populations in 24 infliximab-treated patients with psoriasis/psoriatic arthritis compared to 32 healthy controls. We observed a significant decrease in the frequency of both peripheral natural killer (NK) cells and their subset CD56dimCD16+ NK cells in PsA compared to healthy controls and patients with psoriasis. The latter had a strong positive correlation with PASI in these patients, while CD56brightCD16- NK cells were negatively correlated with PASI. In addition, we observed an upregulation of CD69+ intermediate CD14+CD16+ and CD69+ classical CD14+CD16- monocytes in PsA and increased activity of CD38+ intermediate CD14+CD16+ monocytes in patients with psoriasis. Compared to healthy controls, psoriasis patients demonstrated shifts of the three B cell subsets with a decrease in transitional CD27-CD38high B cells. Our exploratory study indicates a preserved pathophysiological process including continuous systemic inflammation despite clinical stability of the patients treated with infliximab.

Phytochemical characterization and anti-inflammatory activity of a water extract of Gentiana purpurea roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana purpurea was one of the most important medicinal plants in Norway during the 18th and 19th centuries, and the roots were used against different types of gastrointestinal and airway diseases. AIM OF THE STUDY: To explore the content of bioactive compounds in a water extract from the roots, a preparation commonly used in traditional medicine in Norway, to assess the anti-inflammatory potential, and furthermore to quantify the major bitter compounds in both roots and leaves. MATERIALS AND METHODS: G. purpurea roots were boiled in water, the water extract applied on a Diaion HP20 column and further fractionated with Sephadex LH20, reverse phase C18 and normal phase silica gel to obtain the low molecular compounds. 1D NMR, 2D NMR, and ESI-MS were used for structure elucidation. HPLC-DAD analysis was used for quantification. The inhibition of TNF-α secretion in ConA stimulated peripheral blood mononuclear cells (PBMCs) was investigated. RESULTS: Eleven compounds were isolated and identified from the hot water extract of G. purpurea roots. Gentiopicrin, amarogentin, erythrocentaurin and gentiogenal showed dose-dependent inhibition of TNF-α secretion. Gentiopicrin is the major secondary metabolite in the roots, while sweroside dominates in the leaves. CONCLUSIONS: The present work gives a comprehensive overview of the major low-molecular weight compounds in the water extracts of G. purpurea, including metabolites produced during the decoction process, and show new anti-inflammatory activities for the native bitter compounds as well as the metabolites produced during preparation of the crude drug.

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.

A boy in his teens with large ulcerations of the head and neck. / Gutt i tenårene med store ulcerasjoner i hodet og nakken.

BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, has a predilection for the upper airways, lungs and kidneys. However, any other organ can be affected. Although cutaneous lesions are common, they have only rarely been reported as a primary manifestation of the disease. CASE PRESENTATION: We present a case of a teenage boy with pyoderma gangrenosum-like ulcerations of the neck and face. Anti-neutrophil cytoplasmic antibody with antigen specificity for proteinase 3 (PR3-ANCA) was detected. In the absence of other symptoms and organ manifestations, the ulcerations were still considered to be pyoderma gangrenosum. The ulcers started to heal during treatment with corticosteroids and infliximab. One month later the patient developed sinusitis, and eventually lost vision in his left eye. The diagnosis was changed to GPA and he started treatment with methylprednisolone, rituximab and cyclophosphamide with good response on vision, sinusitis and ulcerations. INTERPRETATION: Recognition of this rare skin presentation of GPA is essential, to prevent delays in diagnosis and treatment that can lead to organ damage.

Serum cytokine measurements and biological therapy of psoriasis - Prospects for personalized treatment?

Psoriasis is an immune-mediated disease where the IL-23/Th17 axis as well as TNF comprise main targets of biological therapy. Immune profiling has so far not been embraced as a clinical tool. We aimed to investigate relationships between individual serum cytokine levels in 40 psoriasis patients before and after receiving biological therapy and Psoriasis Area and Severity Index (PASI) and Dermatological Life Quality Index (DLQI). Serum concentration of 25 cytokines was determined by Luminex technology. Mean PASI and DLQI decreased by 71% and 65%, respectively. Increase of IL-2 positively correlated with improvement of PASI and DLQI. Moreover, increase of IL-5, IL-10, IL-12, IL-22 and GM-CSF correlated with treatment effect. Notably, logistic regression revealed four times higher risk of having severe psoriasis when IL-17A increased by 1 pg/mL (OR: 4.06, P < 0.05). Selected serum cytokines might constitute useful biomarkers for monitoring disease activity and optimizing therapeutic strategies in psoriasis patients.

CD11c(+) dendritic cells rather than Langerhans cells are reduced in normal skin of immunosuppressed renal transplant recipients.

The increased risk of squamous cell carcinomas (SCC) in renal transplant recipients (RTR) is related to impaired immunosurveillance as a consequence of immunosuppressive therapy. Since dendritic cells (DC) play an important role in immunosurveillance, we investigated the quantity of DC subsets and macrophages in normal skin of RTR and immunocompetent controls by immunohistochemistry. In this comparative study Langerhans' cells (LC) were present in similar numbers in RTR and controls. The number of CD11c+ DC was significantly reduced in RTR, particularly in patients on triple treatment therapy, compared with controls. Macrophages were significantly increased. Plasmacytoid DC were not detected in normal skin. The reduced quantity of CD11c+ DC and increased number of macrophages in normal skin of immunosuppressed RTR may contribute to the increased incidence of SCC in RTR. This finding underlines the role of DC subsets in immunosurveillance, and may have implications for our understanding of the effect of immunosuppression on DC subsets.