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

Project Details

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 characterize 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 Stradins Clinical University Hospital compared to the healthy individuals. The findings of this study will contribute significantly to understanding of IgAN pathogenesis, and may enable patient subtyping for disease management and limit disease progression, and ultimately the discovery of non-invasive disease-specific biomarkers for earlier diagnosis and development of new therapies.
StatusActive
Effective start/end date1/01/2030/06/23

Keywords

  • Immunoglobulin A nephropathy
  • chronic kidney disease
  • autoimmunity
  • B cells; microbiome

Field of Science

  • 3.2 Clinical medicine

Smart Specialization Area

  • Biomedicine, medical technologies and biotechnology

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