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Dissecting the interplay between intestinal dysbiosis and B cell function in the pathogenesis of immunoglobulin A nephropathy

Project/agreement No.
lzp-2019/1-0139
Project funding
299 799.00 EUR
Project realization
02.01.2020. - 31.12.2022.

Aim

The aim is to investigate the interplay between intestinal dysbiosis and B cell function in the pathogenesis of IgA nephropathy.

Description

Immunoglobulin A nephropathy (IgAN) is an autoimmune disease and the most common form of primary glomerulonephritis. Patients present with heterogeneous clinicopathological manifestations and variable prognosis. The mechanisms of IgAN pathogenesis remain poorly defined but both B cells and microbiota are implicated. Our study will be the first to characterise the peripheral B cell subsets and function and explore possible interplay with intestinal microbiome diversity in IgAN patients. It is likely that intestinal dysbiosis in IgAN leads to aberrant B cell activation and differentiation towards antibody-producing plasma cells as opposed to regulatory B cells. This is in turn associated with a break in tolerance in IgAN pathogenesis. We will investigate peripheral B cell phenotype by flow cytometry and function in vitro, sequence the fecal microbiome, assess bacterial translocation markers and gut-derived uremic toxins in patients with histologically proven IgAN selected from renal biopsy registry at Pauls Stradiņš Clinical University Hospital compared to healthy individuals. The findings of this study will significantly contribute to understanding IgAN pathogenesis, and may enable patient subtyping for disease management and limit disease progression, and ultimately to the discovery of non-invasive disease-specific biomarkers for earlier diagnosis and development of new therapies.

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Project working group meeting. From the right: Viktorija Kuzema, dr. Kārlis Rācenis, dr. Baiba Šlisere, lead researcher Kristīne Oļeiņika, dr. Anna Popova, dr. Aiga Vasiļvolfa