Background: Simultaneous kidney-pancreas transplantation (SKP Tx) is performed as treatment option for type-1 diabetes with end stage kidney diseases. Though allograft survival was improved with advanced surgical procedures and immune suppressive regimens, acute/chronic antibody (Ab) mediated rejection is a major risk factor for poor allograft function in SKP Tx. Goal of this study is to determine the role of immune responses to kidney (KSAg) and pancreas self-antigens (PSAg) in allograft rejection following SKP Tx.

Methods: Sera were collected from 30 SKP Tx recipients. Pre, post-transplant Abs to KSAgs (Collagen-IV (Col-IV), fibronectin (FN)) and PSAgs (insulin, islet cell, glutamic acid decarboxylase (GAD) and pancreatitis associated protein 1 (PAP-1) were measured by ELISA. Abs concentration was calculated using a standard curve from known concentrations of kidney and pancreas Abs. The sample was considered positive if the values above mean+2X standard deviation of healthy normal subjects. Antigen specific CD4+ T cells secreting cytokines were measured by ELISPOT.

Results: Biopsy-proven acute rejection episodes of the kidney and/or pancreas allografts occurred in 12/30 patients. 6/12 patients had combined kidney pancreas rejection, 2/12 had kidney-alone and 4/12 with pancreas-alone rejections. Pre, post-transplant serum Ab concentration of rejected groups was compared with 18 SPK Tx stable controls. Abs to KSAg and PSAg were significantly higher in post-transplant in SKP with rejection compared with stable controls. Elispot results showed increased frequency of IFNγ and IL-17 with reduction in IL-10 secreting cells in SKP Tx with rejection groups, while reduced IFNγ and IL-17 with increased in IL-10 secreting cells were observed in SKP Tx stable controls.

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