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Abstract: SA-PO351

B-Cell Profiles in FSGS Rituximab Responders with T-Cell Hyporesponsiveness

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Chan, Chang-Yien, National University of Singapore, Singapore, Singapore
  • Liu, Isaac, National University of Singapore, Singapore, Singapore
  • Lam, Kong Peng, Bioprocessing Technology Institute, A*STAR , SINGAPORE, Singapore
  • Ng, Kar Hui, National University of Singapore, Singapore, Singapore
  • Yap, Hui Kim, National University of Singapore, Singapore, Singapore
Background

We recently reported a subgroup of focal segmental glomerulosclerosis (FSGS) patients bearing an immunological signature of T-cell hyporesponsiveness who responded to rituximab treatment, suggesting a possible role of B-T cell interactions in modulating podocyte injury. This study aimed to investigate the B-cell profiles in this subgroup of immune-mediated FSGS.

Methods

At baseline before rituximab treatment, FSGS patients were stratified into the hyporesponsive T-cell activation (HT) and non-HT groups. HT group is defined by activated IFN-γ+CD3+ expression <2.5% following PMA and ionomycin stimulation. Blood samples were washed thrice before staining of B-cell subsets using lysed whole blood method. B-cells were isolated using CD19 microbeads and stimulated with lipopolysaccharide (LPS) for 4 hours. Cytokine levels in culture supernatants were quantified using multiplex suspension bead array system.

Results

19 FSGS patients receiving rituximab were recruited of which 11 patients were in the HT group. At baseline, the FSGS HT group showed significantly higher percentage of double negative (DN) memory B cells (CD19+CD27-IgD-) (7.8±1.1%) compared to FSGS non-HT patients (3.8±0.6%) (P=0.009), although this did not reach statistical significance compared to 14 controls (4.8±0.6%) (P=0.08) and 12 patients with minimal change disease (MCD) (5.8±0.9%) (P=0.2). Following stimulation, of the 27 cytokines analysed, B-cell production of IL-4, IL-9 and IL-10 levels were also significantly higher in FSGS HT group compared to non-HT group (Table 1). Among these cytokines, only IL-4 and IL-10 levels in FSGS HT group were significantly higher than MCD.

Conclusion

FSGS rituximab responders with HT phenotype demonstrated elevated DN memory B cells, IL-4 producing Be-2 cells and IL-10 producing regulatory B-cells, possibly explaining the T-cell hyporesponsiveness.

Funding

  • Government Support - Non-U.S.