Effector CD4+ T cell subsets in Takayasu arteritis - Differences between the peripheral blood and the aorta.

Takayasu arteritis (TAK) is a granulomatous vasculitis that affects large arteries. T cells are important in TAK pathophysiology as these cells orchestrate granulomatous infiltration in arteries. This study aims to evaluate effector CD4+ T cells in the peripheral blood and the aortic wall of TAK patients and to analyze associations with disease activity and therapy. We performed a longitudinal study including 30 TAK patients and 30 controls. CD3+ T cells, CD3+CD4- T cells, CD4+ T cells, and Th1, Th2, and Th17 cells were evaluated in peripheral blood by flow cytometry, and the expression of CD4, CD8, Tbet, GATA-3, and RORγT was analyzed in the aorta of 6 patients by immunohistochemistry. TAK patients presented lower CD3+ T cells and CD4+ T cells (p=0.031 and p=0.039, respectively) than controls. Patients with active disease and those in remission had higher proportions of Th17 cells than controls (p=0.016 and p=0.004, respectively). Therapy for TAK did not result in significant differences concerning CD4+ effector T cell subpopulations. Disease duration correlated with the number and percentage of Th2 cells (rho=-0.610 and rho=-0.463, respectively) and with Th17 cells (rho=-0.365 and rho=-0.568). In the aorta, the expression of CD8 was higher than CD4, whereas GATA-3, Tbet and RORγT were expressed in this order of frequency. In conclusion, TAK patients present an increased Th17 response in the peripheral blood regardless of disease activity, whereas in the aortic tissue CD8 cells and the Th2 response were predominant.

Immunoexpression of HER2 pathway related markers in HER2 invasive breast carcinomas treated with trastuzumab.

PURPOSE: We evaluated the immunoexpression of potential markers involved in the HER2 pathway in invasive breast carcinoma with HER2 amplification treated with trastuzumab. METHODS: Samples of ninety patients diagnosed and treated at two public Brazilian hospitals with overexpressed invasive carcinoma between 2009 and 2018 were included. Several markers (Bcl-2, CDK4, cyclin D1, EGFR, IGF1, IGF-1R, MDM2, MUC4, p16, p21, p27, p53, PTEN, RA, TNFα, and VEGF) were immune analyzed in the tumor by immunohistochemistry and then correlated with clinicopathological variables. RESULTS: Tumor sample expression results determined potential markers of good prognosis with statistically significant values: cyclin D1 with a nuclear grade, and recurrence; IGF-1 with tumor size, and death; p16 with a response after treatment; PTEN with a response after treatment, and death. Markers of poor prognosis: p53 with histological, and nuclear grade; IGF-1R with a compromised lymph node. The treatment resistance rate after trastuzumab was 40%; the overall survival was 4.13 years (95% CI 5.1-12.5) and the disease-free survival was 3.6 years (95% CI 5.1-13.1). CONCLUSIONS: The tumor samples profile demonstrated that cyclin D1, IGF-1, p16, and PTEN presented the potential for a good prognosis and p53 and IGF-1R for worse.