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Abstract: TH-PO0445

Evaluating Interactions of B Cells and T Cells in Immune-Mediated Glomerular Diseases

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Simpson, Jenna, Columbia University, New York, New York, United States
  • Sen, Leuna, Columbia University, New York, New York, United States
  • Pathak, Sharvari, Columbia University, New York, New York, United States
  • Stevens, Kelsey O., Columbia University, New York, New York, United States
  • Steers, Nicholas J., Columbia University, New York, New York, United States
Background

Immune mediated glomerular diseases (IMGD) including IgA Nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) share clinical presentations. The immune mechanisms that contribute the to IMGD are poorly understood, however recently the dysregulation of B-cells has been proposed to be a critical factor.

Methods

We studied IgAN (n=10), MN (n=10), FSGS (n=7), and MCD (n=7) patients and healthy controls (HC, n=10). Utilizing cell sorting, the circulating T-follicular like helper (cT-FH) cells and naïve B-cells were collected to evaluate the cT-FH cell – naïve B-cell interactions. Cells were cultured for 6-days in the presence of a cognate antigen, and immunoglobulins and cytokines were measured in the cell culture supernatant using LEGENDplex. Flow cytometry evaluated B-cells in the circulation.

Results

Using the LEGENDplex bead-based immunoassay we measured the concentration of IL-5, IL-13, IL-2, IL-6, IL-10, IL-17A, IL-17F, IL-4, and TNF-α, secreted into the cell culture supernatant. There were significantly decreased concentrations of IL-6 and IL-4 (P < 0.05, one way ANOVA), and a significant increase in the IL-5 concentration (P < 0.05, one way ANOVA) in cells derived from IgAN patients compared to HC, MN, FSGS, and MCD patients. A significant increase was observed in the IL-10 concentration (P < 0.05, one way ANOVA) in cells derived from FSGS and MCD patients compared to HC and IgAN patients. Analysis of the immunoglobulins demonstrated increased secretion of IgA into the cell culture supernatants derived from IgAN patients compared to HC, and MN, FSGS, and MCD patients (P < 0.01, one way ANOVA), and no differences in the IgG isotypes were observed. This may begin to explain the increased numbers of IgA antibody secreting cells observed in the peripheral blood of IgAN patients compared to MN, MCD, and FSGS patients, and HC.

Conclusion

Our data determined cytokine profiles generated from the cT-FH cell – naïve B-cell interactions have the potential to influence immunoglobulin production in the setting of IMGD, that needs to be experimentally validated.

Funding

  • NIDDK Support