Table 1.

Immune biomarkers in pancreas and islet transplantation

	Biomarker	Test	Function	Application	Ref
Early inflammatory response	CCL2/MCP-1	ELISA	Donor serum levels negatively associated with graft survival for thrombosis	Simultaneous kidney-pancreas transplantation	[12]
	HMGB1	ELISA	Recipient serum levels indicate islet damage and poor outcome	Islet autotransplantation	[15]
Humoral immunity	GADA, IA2A and ZnT8A	Radiobinding and Immunoprecipitation assay	Post transplant changes predictive of the outcome	Islet allotransplantation Pancreas transplantation	[33] [34; 35]
	Class I and II PRA	FlowPRA beads + single antigen beads for cytometry	Sensitized patients showed inferior outcome	Islet allotransplantation	[39]
	PRA and DSA	Single antigen beads for Luminex	Concomitant PRA and DSA increase, or DSA alone, reduce graft survival De novo alloantibodies increment is associated with poorer pancreas graft survival	Islet allotransplantation Pancreas transplantation Pancreas-kidney transplantation	[37] [41;42]
Cellular immunity	IA-2, GAD65, insulin reactive T cells	3H thymidine proliferation	Pre-transplant autoreactivity associated to loss of function	Islet allotransplantation	[49] [31]
	GAD65 reactive T cells	MHC I and II multimers	Post-transplant expansion indicate autoimmunity recurrence	Islet allotransplantation Pancreas Transplantation	[50] [51]
	Alloreactive lymphocytes cytokine profiles	Luminex of cytokines secreted by MLC	IL-10+ regulatory T cells associated with insulin independence	Islet allotransplantation	[54]
	GAD65, InsulinB, IA2, PPI, IGRP, ppIAPP autoreactive CD8+ T cells	Quantum dot conjugated HLA2 multimer staining	Preproinsulin autoreactive CD8+ T circulating cells are associated with autoimmune mediated beta-cell destruction Association between autoreactivity and transplantation outcome Circulating CD8+ T cells parallel the specificity of intrapancreatic CD8+ T cells	Islet allotransplantation Pancreas transplantation	[55] [56]

Abbreviations: CCL2, chemokine (C-C motif) ligand 2; MCP-1, monocytes chemotactic protein 1; ELISA Enzime-linked immunosorbent assay; HMGB1, high mobility group box 1; GADA, glutamic acid decarboxylase 65 autoantibodies; IA2A, insulinoma-associated protein 2 autoantibodies; ZnT8A, zinc transporter 8 antigen autoantibodies; PRA, panel reactive antibodies; DSA, donor-specific antibodies; GAD65, glutamic acid decarboxylase 65; MHC, major histocompatibility complex; MLC, mixed lymphocyte cultures; IL-10, interleukin 10; IL-2, interleukin 2; PPI, preproinsulin; IGRP, islet specific glucose-6-phospatase catalytic subunit-related protein; ppIAPP, prepro-islet amyloid polypeptide; HLA2, human leukocyte antigen 2