Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection

Transpl Int. 2012 Oct;25(10):1050-8. doi: 10.1111/j.1432-2277.2012.01531.x. Epub 2012 Jul 17.

Abstract

The contribution of T cells and graft-reactive antibodies to acute allograft rejection is widely accepted, but the role of graft-infiltrating B and plasma cells is controversial. We examined 56 consecutive human renal transplant biopsies classified by Banff schema into T-cell-mediated (N = 21), antibody-mediated (N = 18), and mixed (N = 17) acute rejection, using standard immunohistochemistry for CD3, CD20, CD138, and CD45. In a predominantly African-American population (75%), neither Banff classification nor C4d deposition predicted the return to dialysis. Immunohistochemical analysis revealed CD3(+) T cells as the dominant cell type, followed by CD20(+) B cells and CD138(+) plasma cells in all acute rejection types. Using univariate Cox Proportional Hazard analysis, plasma cell density significantly predicted graft failure while B-cell density trended toward significance. Surprisingly T-cell density did not predict graft failure. The estimated glomerular filtration rate (eGFR) at diagnosis of acute rejection also predicted graft failure, while baseline eGFR ≥6 months prior to biopsy did not. Using multivariate analysis, a model including eGFR at biopsy and plasma cell density was most predictive of graft loss. These observations suggest that plasma cells may be a critical mediator and/or an independently sensitive marker of steroid-resistant acute rejection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antigens, CD20 / biosynthesis
  • B-Lymphocytes / immunology
  • Biopsy / methods
  • CD3 Complex / biosynthesis
  • Complement C4b / biosynthesis
  • Female
  • Glomerular Filtration Rate
  • Graft Rejection
  • Humans
  • Immunohistochemistry / methods
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Peptide Fragments / biosynthesis
  • Plasma Cells / cytology*
  • Proportional Hazards Models
  • Renal Insufficiency / therapy*
  • Syndecan-1 / biosynthesis
  • Transplantation, Homologous

Substances

  • Antigens, CD20
  • CD3 Complex
  • Peptide Fragments
  • Syndecan-1
  • Complement C4b
  • complement C4d