The Significance of IgG4 Positive Plasma Cells in Renal Transplant Biopsies with Plasma Cell Rich Acute Cellular Rejection
Gabrielle Rizzuto, Thuy Nguyen, Kuang-Yu Jen, Zoltan Laszik. UCSF, San Francisco, CA
Background: Morphologic criteria have recently been established for IgG4-tubulointerstitial nephritis in native kidneys. However, no data are available about the potential existence and significance of IgG4-positive plasma cells following renal transplantation. Plasma cell rich acute cellular rejection (ACR) has a less favorable outcome than conventional ACR, the reasons for which are unclear. Here, we assess the IgG4 positive plasma cell load in transplant kidney biopsies with plasma cell rich ACR and also in cases with concurrent antibody-mediated rejection (ACR/AMR).
Design: Renal transplant biopsies were selected from computerized departmental files 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. Immunofluorescent staining for IgG4, CD20, CD3, CD8, and CD68 were performed on formalin-fixed and paraffin-embedded tissues and cell density quantitatively assessed using computer-assisted morphometric analysis.
Results: Quantitative cell density analysis revealed a significant increase in IgG4 positive cells in plasma cell rich rejection biopsies compared to control biopsies (p=0.002), and the data support the potential existence of two subsets of IgG4 positive plasma cell rich rejection: IgG4-rich and IgG4-poor subsets. Overall, significantly fewer IgG4 positive cells were present in plasma cell rich ACR/AMR compared to plasma cell rich ACR alone (p=0.04). Statistically significant differences in B cell (CD20), T cell (CD3, CD8), and macrophage (CD68) density were not observed between the groups.
Conclusions: These findings establish the existence of an IgG4 plasma cell population in many, but not all, cases of plasma cell rich ACR. That IgG4 plasma cells are present in significantly fewer cases of plasma cell rich ACR/AMR suggest a possible pathogenic difference between pure ACR and ACR/AMR. Future work to correlate IgG4 positive plasma cell rejection, particularly IgG4-rich and IgG4-poor subsets, with clinical outcome is warranted.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 280, Wednesday Afternoon