Development of immune response to tissue-restricted self-antigens in simultaneous kidney-pancreas transplant recipients with acute rejection

Muthukumar Gunasekaran, Neeta Vachharajani, Joseph P. Gaut, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, William C. Chapman, Jason Wellen, Thalachallour Mohanakumar

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4 Scopus citations

Abstract

Simultaneous kidney-pancreas transplantation (SKP Tx) is a treatment for end-stage kidney disease secondary to diabetes mellitus. We investigated the role of immune responses to donor human leukocyte antigens (HLA) and tissue-restricted kidney and pancreas self-antigens (KSAgs and PSAgs, respectively) in SKP Tx recipients (SKP TxRs). Sera collected from 39 SKP TxRs were used to determine de novo Abs specific for KSAgs (collagen-IV, Col-IV; fibronectin, FN) and PSAgs (insulin, islet cells, glutamic acid decarboxylase, and pancreas-associated protein-1) by ELISA. KSAg-specific IFN-γ, IL-17, and IL-10 cytokines were enumerated by ELISpot. Abs to donor HLA classes I and II were determined by Luminex assay. Abs to KSAgs and PSAgs were detectable in recipients with rejection compared with stable recipients (P<.05). Kidney-only rejection recipients had increased Abs against KSAgs compared with stable (P<.05), with no increase in Abs against PSAgs. Pancreas-only rejection recipients showed increased Abs against PSAgs compared to stable (P<.05), with no Abs against KSAgs. SKP TxRs with rejection showed increased frequencies of KSAg-specific IFN-γ and IL-17 with reduction in IL-10-secreting cells. SKP TxRs with rejection developed Abs to KSAgs and PSAgs demonstrated increased frequencies of kidney or pancreas SAg-specific IFN-γ and IL-17-secreting cells with reduced IL-10, suggesting loss of peripheral tolerance to SAgs.

Original languageEnglish
Article numbere13009
JournalClinical Transplantation
Volume31
Issue number8
DOIs
StatePublished - Aug 2017

Keywords

  • IFN-γ
  • IL-17
  • kidney self-antigens
  • pancreas self-antigens
  • simultaneous kidney and pancreas transplants

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