T-bet+ Lymphocytes and IgG4+ Plasma Cells Correlate with Poor Clinical Outcome in Plasma Cell Rich Acute Cellular Renal Transplant Rejection
Gabrielle Rizzuto, Thuy Nguyen, Kuang-Yu Jen, Gyula Szabo, Allison Webber, Zoltan Laszik. University of California, San Francisco, CA
Background: We previously reported the existence of IgG4+ plasma cells in many, but not all, cases of plasma cell rich acute cellular rejection (ACR). Both total plasma cell load and IgG4+ plasma cell load is significantly increased in biopsy specimens with less favorable clinical outcome. Here, we assess the regulatory T cell (Foxp3+), NK cell (CD56+), and Th1 cell (T-bet+) load in transplant kidney biopsies with plasma cell rich ACR and in cases with concurrent antibody-mediated rejection (ACR/AMR).
Design: Renal transplant biopsies were selected for the following study groups: plasma cell rich ACR (n=20), plasma cell rich ACR/AMR (n=7), control ACR (n=8), and control ACR/AMR (n=5). Only cases without concurrent glomerular or tubulointerstitial disease, other than acute rejection, were considered for the study. Immunostaining for Foxp3, CD56, and T-bet was performed on formalin-fixed and paraffin-embedded tissues and cell density quantitatively assessed using computer-assisted morphometric analysis. These new data were correlated with our previously quantified inflammatory cell burden (IgG4, CD20, CD3, CD8, CD68) and Collagen-III for the same sample set, and with clinical outcome (less favorable outcome defined as dialysis or Creatinine > 2.0).
Results: A significant increase in the density of T-bet+ cells is observed in plasma cell rich rejection biopsies compared to control biopsies (p=0.003) and there is a trend toward increased Foxp3+ cells in plasma cell rich rejection biopsies compared to control biopsies (p=0.09). No significant difference in CD56+ cell density is seen among the groups. Total T-bet+ cell load is increased in biopsy specimens with less favorable clinical outcome (p=0.028), and a positive correlation between T-bet+ and IgG4+ plasma cell load is observed for cases where IgG4+ plasma cells are identified (r=0.35, p=0.07). No trend is identified between the presence of IgG4+ plasma cells and the other parameters (CD56+, FoxP3+ cells), and these other parameters do not correlate with clinical outcome.
Conclusions: These findings establish the existence of significant numbers of Th1 cells and regulatory T cells in many, but not all, cases of plasma cell rich ACR. Data support a positive correlation between the presence of Th1 cells and IgG4 plasma cells and suggest a correlation between the presence of these particular immune cells and less favorable clinical outcome.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 219, Monday Afternoon