RESUMO
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.
Assuntos
Leucócitos Mononucleares/imunologia , Psoríase/imunologia , Linfócitos T Citotóxicos/imunologia , Células Th17/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Memória Imunológica/imunologia , Inflamação/sangue , Inflamação/imunologia , Interleucina-12/imunologia , Interleucina-17/imunologia , Interleucina-23/imunologia , Masculino , Monócitos/imunologia , Transdução de Sinais/imunologiaRESUMO
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.