Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis that has heterogeneous clinicopathological manifestations and variable prognosis. Approximately 20% of patients diagnosed with IgAN at Pauls Stradins Clinical University Hospital (PSCUH) initiate dialysis within a year following diagnosis. However, the mechanisms of IgAN pathogenesis remain poorly defined, no specific treatment exists. The aim of the research is to characterize the phenotype and function of the B cell compartment, the gut microbiome composition and markers of bacterial translocation in IgAN patients compared to healthy individuals, and the interplay between intestinal dysbiosis and B cell function in the pathogenesis of IgA nephropathy. Prospective study is conducted in PSCUH Nephrology Centre. Adults with a morphologically confirmed (primary) IgAN are included in the study, divided in groups (20 persons in each) according to glomerular filtration rate and method of renal replacement therapy. Fifty age-, sex- and ethnicity-matched healthy individuals will be in a control group. We will investigate peripheral B cell subsets by flow cytometry, assess B cell phenotype by immunofluorescence staining in renal biopsies, and analyze the effect of bacteria/bacterial products /uremic toxins on B cells in vitro; furthermore, perform sequencing of the fecal microbiome, assess bacterial translocation markers and gut-derived uremic toxins. Project has started the implementation in January 2020. We expect, that this study will be one of the first investigations of the link between B cell responses and dysbiosis in IgAN. Investigation of gut microbiome for the first time in Baltic countries will be carried out for patients with autoimmune kidney disease (IgAN). The findings may also provide clues to which patients may benefit from B cell-depleting agents as well as identify novel targets for the development of IgAN-specific therapies.
- 3.4. Other publications in conference proceedings (including local)