ASSESSMENT OF RISK FACTORS AND RATE OF PROGRESSION OF PRIMARY GLOMERULOPATHIES

Purpose of the study: to determine the rate of progression of primary chronic glomerulopathies (GP) in children and to establish the main risk factors for the development of this process. Materials and methods. 188 children who were under observation and treatment at the Republican Center for Pediatric Nephrology and Renal Replacement Therapy of the "2nd Children's City Clinical Hospital" in Minsk, aged 3 to 17 years, with morphologically verified kidney damage, were included in the study: group №1 - children with minimal change disease (MCD), n=53; group №2 with IgM nephropathy (IgMN), n=26; group №3 with focal segmental glomerulosclerosis (FSGS), n=55; group №4 with IgA nephropathy (IgAN), n=54.The duration of the period from the onset of the disease to reaching the 3rd stage of CKD and predictors that determine the rate of progression of GP using Kaplan-Meier method was studied. Results. Anamnestic, clinical, laboratory, immunological (blood concentration of markers of T and B lymphocyte activation RANTES and BAFF), proinflammatory (caspase 1, IL1β and TNFα), vascular (VEGF) and tissue (TGF1β) growth factors), metabolic status (adiponectin, leptin, obestatin, vitamin D 25 (OH) D), instrumental, morphological changes were analyzed. Each of the variables was considered as a likely risk factor for the progression of GP. Conclusion. A mathematical model has been developed for predicting the risk of progression of secondary GP in children, including risk factors as predictors: impaired renal function at the onset of the disease, non-compliance with therapy, and a decrease in the estimated glomerular filtration rate (eGFR) at the onset of the disease less than 87 ml/min. The predictive accuracy of the model was 90,9% (95%ДИ 79,3-100%).

Antigen-driven PD-1+TOX+EOMES+ and PD-1+TOX+BHLHE40+ synovial T lymphocytes regulate chronic inflammation in situ

Introduction/AbstractT lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro1–29. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA)30–33. However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the heterogeneity of synovial T lymphocytes in JIA patients by single cell RNA-sequencing. We identify subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1+TOX+EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+TOX+BHLHE40+ population of CD4+, and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.