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Abstract: TH-PO0440

Immunophenotyping Circulating IgA-Positive B Cells for B-Cell-Activating Factor (BAFF)/Transmembrane Activator and CAML Interactor (TACI) Receptor Expression to Inform Therapeutic Decisions in IgAN

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Fernandez Lorente, Maria Loreto, Clinica Universidad de Navarra, Pamplona, Navarre, Spain
  • Nguyen, Victoria V., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • McKee, Sarah L., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Chen, Dhruti P., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Bunch, Donna O., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Hu, Yichun, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Hogan, Susan L., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Derebail, Vimal K., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Falk, Ronald, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Saha, Manish K., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Background

IgA nephropathy (IgAN) therapy is being redefined by drugs that alter interaction of BAFF and APRIL with their receptors, including BAFF-R and TACI, on B cells. Currently, there are no validated biomarkers to accurately identify patient populations that would have the best clinical benefits from such therapeutics. B cell immunophenotyping may help to tailor this new therapies.

Methods

Peripheral blood mononuclear cells (PBMCs) from 31 patients with biopsy-proven IgAN off immunosuppression were included. CureGN definitions for active disease and remission were used. We compared 21active (A), 10 remission (R), and 9 healthy controls (HC) to identify BAFF-R and TACI surface markers on B cells using spectral flow cytometry. Data was analyzed in Flow Jo and medians were compared. Non-parametric Kruskal-Wallis test was used.

Results

IgA+CD19+ B cells were higher in IgAN than HCs (A 10%, R 11%, and HC 5%, p = 0.09), whereas total CD19+ were lower (A 4%, R 3%, and HC 7%, p = 0.05). IgAN patients had higher TACI expression (A 47%,R 52%, HC 27%, p=0.006) and BAFF-R (A 97%, R 95%, and HC 74.5%, p = 0.06) on total CD19+ B cells. Within IgA+CD19+ B, both A and R patients had significantly higher expression of TACI compared to HC (active 8%, remission 8% vs HC 3.5%, p=0.01); however, expression of BAFF-R+ was lower(8% and 7% vs 15%, p=0.05) (Figure1). A and R immunophenotypes did not differ from each other.

Conclusion

TACI expression is elevated in total B cells in IgAN patients. Among IgA+ B cells, patients had lower BAFF-R expression but higher of TACI regardless of A or R disease state. IgAN patients had a wide range of TACI and BAFF-R expression on IgA+ B cells, suggesting that not all patients may be good candidates for treatment with drugs targeting these receptors/ ligands. Immunophenotyping should be evaluated for its ability to stratify patients to predict therapeutic response.

Funding

  • Clinical Revenue Support