Abstract: TH-PO039

IgA Nephropathy Patients B Cells Producing IgA Exhibit High Epstein-Barr Virus Infection Rate in Comparison to Disease and Healthy Controls

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Zachova, Katerina, Palacky University Olomouc, Olomouc, Czechia
  • Raska, Milan, University of Alabama at Birmingham , Birmingham, Alabama, United States
Background

IgAN is the most common form of primary glomerulonephritis worldwide and is typical for deposition of immune complexes mostly of IgA-IgG in the glomerular mesangium. The mesangial IgA is exclusively of the IgA1 subclass and is aberrantly glycosylated in its hinge region (galactose deficient IgA1 – gd-IgA1). EBV infects preferentially B cells, mostly the precursors of IgA-producing cells in peripheral blood. That implies the possibility that EBV infection is somehow involved in Gd-IgA1 production. Relations between some autoimmune diseases (multiple sclerosis, diabetes mellitus) and Epstein Barr virus (EBV) infection were already described in several papers. Therefore it was obvious to focus on the impact of EBV infection on IgA nephropathy (IgAN).

Methods

By cell surface staining with monoclonal antibodies we analyzed B cell subpopulations to naive, regulatory, memory, plasmablast, and plasma cell and surface immunoglobulin subpopulations IgA, IgG from peripheral blood of IgAN patients, disease controls and healthy subjects. Using a specific approach combining cell surface staining with in situ hybridisation for EBV RNA (EBER) followed by flow cytometry analyses we made several observations.

Results

EBV infects preferentially IgA+ B cells followed by IgG+ B cells in either IgAN patients and in controls. Nevertheless, the incidence of EBV+ IgA and also EBV+ IgG B cells in peripheral blood of the IgAN patients is more than 10x higher than in non IgAN patients. Furthermore plasmablasts are the most EBV-infected cells (65%) following with memory cells (35%) in IgAN patients in contrasts to 100% of plasmablasts in non IgAN patients. No naive and regulatory B cells were observed to be EBV positive in any groups. These explorations were confirmed on IgA deficient patients, having low amounts of IgA in serum but still having IgA B cells (naive and memory) in peripheral blood. Analysis of those patients showed 10x lower co-incidence of IgA-EBV+ cells. That clearly corresponds with our analysis showing that 2/3 of EBV+ cells are plasmablasts.

Conclusion

Our data confirmed an important impact of EBV infection on IgA nephropathy. From these results it is clear that B cells producing IgA of IgAN patients exhibit high Epstein-Barr virus infection rate in comparison to disease and healthy controls.

Funding

  • Government Support - Non-U.S.