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Development of immune response to tissue‐restricted self‐antigens in simultaneous kidney‐pancreas transplant recipients with acute rejection
Author(s) -
Gunasekaran Muthukumar,
Vachharajani Neeta,
Gaut Joseph P.,
Maw Thin Thin,
Delos Santos Rowena,
Shenoy Surendra,
Chapman William C.,
Wellen Jason,
Mohanakumar Thalachallour
Publication year - 2017
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.13009
Subject(s) - medicine , kidney , immune system , pancreas , antigen , kidney disease , diabetes mellitus , endocrinology , immunology
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 ( KSA gs and PSA gs, respectively) in SKP Tx recipients ( SKP TxRs). Sera collected from 39 SKP TxRs were used to determine de novo Abs specific for KSA gs (collagen‐ IV , Col‐ IV ; fibronectin, FN ) and PSA gs (insulin, islet cells, glutamic acid decarboxylase, and pancreas‐associated protein‐1) by ELISA . KSA g‐specific IFN ‐γ, IL ‐17, and IL ‐10 cytokines were enumerated by ELIS pot. Abs to donor HLA classes I and II were determined by Luminex assay. Abs to KSA gs and PSA gs were detectable in recipients with rejection compared with stable recipients ( P <.05). Kidney‐only rejection recipients had increased Abs against KSA gs compared with stable ( P <.05), with no increase in Abs against PSA gs. Pancreas‐only rejection recipients showed increased Abs against PSA gs compared to stable ( P <.05), with no Abs against KSA gs. SKP TxRs with rejection showed increased frequencies of KSA g‐specific IFN ‐γ and IL ‐17 with reduction in IL ‐10‐secreting cells. SKP TxRs with rejection developed Abs to KSA gs and PSA gs demonstrated increased frequencies of kidney or pancreas SA g‐specific IFN ‐γ and IL ‐17‐secreting cells with reduced IL ‐10, suggesting loss of peripheral tolerance to SA gs.