Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 as a Marker of Acute Rejection in Pancreas Allotransplantation in Pigs

Background/AimsAn early, simple, and reliable marker for acute pancreatic allograft rejection is not available. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) is an interleukin-6–dependent acute-phase positive protein that can act as an anti-inflammatory protein. We studied the response of the ITIH4 in pigs undergoing pancreas allotransplantation (PT) and evaluated this protein as a biomarker for acute graft rejection.MethodsPT with enteric drainage of the exocrine secretion and systemic venous drainage was performed on 12 Landrace pigs. No immunosuppression was administered. Serum concentrations of glucose, amylase, lipase, insulin, C-peptide, and ITIH4 were determined daily.ResultsThe response of ITIH4 to PT was early, intense, and prolonged, with 2 peaks in serum concentration. The first peak, which started on day 1 and reached maximum (around 6 mg/dL) on day 3, was attributed to the systemic acute phase response to surgical stress. The second peak, which exceeded the first peak and reached maximum (>8 mg/dL) on day 6, began when the recipients were still normoglycemic, and preceded onset of the diabetic state caused by acute graft rejection by an average of 4 days.ConclusionSerum ITIH4 could help to predict subclinical acute graft rejection after PT in pigs.