Abstract: FR-OR138
The Effect of Pulse Steroids/IVIG/Rituximab on Circulating Lymphocytes and Cytokines in Kidney Transplant Recipients with Chronic Active ABMR)
Session Information
- Translational and Transplant Pathology
October 26, 2018 | Location: 6E, San Diego Convention Center
Abstract Time: 05:42 PM - 05:54 PM
Category: Transplantation
- 1802 Transplantation: Clinical
Authors
- Wilson, Nancy A., University of Wisconsin, Madison, Wisconsin, United States
- Bath, Natalie M., University of Wisconsin, Madison, Wisconsin, United States
- Panzer, Sarah E., University of Wisconsin Madison, Madison, Wisconsin, United States
- Djamali, Arjang, School of Medicine and Public Health, Madison, Wisconsin, United States
- Reese, Shannon, University of Wisconsin, Madison, Wisconsin, United States
Background
There is no information on the effect of combination therapy with pulse steroids/IVIG/Rituximab on circulating T-cell and B-cell phenotypes and cytokines in kidney transplant recipients (KTR) with chronic active antibody mediated rejection (cABMR).
Methods
We examined this questions in 8 KTR with cABMR who underwent follow up evaluation with a repeat protocol biopsy within 3 months of the initial diagnosis. PBMC subsets were identified using flow cytometry. Plasma was analyzed using Luminex 45-plex assay for cytokines. Paired Wilcoxon rank sum test was utilized to assess the effect of therapy on pre and post samples. Pre-treatment samples were also compared to a group of 11 healthy volunteers matched for age, gender, and race.
Results
Median age at the diagnosis of cABMR was 48 years. The diagnosis was made at a median of 9.8 years post-transplant. Median Scr and urine PC at biopsy were 2.43 mg/dL and 1.24 g/g. Treatment with pulse steroids/IVIG/Rituximab was associated with a statistically significant decline in ptc and mvi Banff scores (p<0.05) at the three-month protocol biopsy. Similarly, B cells, Naïve B cells, plamablasts, and transitional B cells were significantly reduced (p<0.05 for all). However, treatment was associated with a significant increase in CD3 T cells and IL17 levels (p=0.02 for both). There was no significant difference in other Banff scores, kidney function, and Treg or Breg populations. Compared to controls, KTR had significantly lower naïve B cells, plasmablasts, and transitional B cells, while cirtculating fractaline, IL1-alpha, IL7, IL13, IL15, PDL1, and VEGF levels were significantly increased (p<0.04 for all).
Conclusion
In conclusion, KTR with ABMR have significantly different circulating B cell and cytokine profiles than healthy volunteers. Short term therapy with Pulse steroids/IVIG/Rituximab effectively inhibits disease activity in cABMR. However, treatment is associated with an upregulation of T cell response suggesting a negative feedback role for B cells in cABMR.