A pilot study on the immunological effects of oral administration of donor major histocompatibility complex class II peptides in renal transplant recipients

• Published in: Clinical transplantation Vol. 22; no. 6; pp. 754 - 759
• Main Authors: Womer, Karl L, Magee, Colm C, Najafian, Nader, Vella, John P, Milford, Edgar L., Sayegh, Mohamed H, Carpenter, Charles B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2008; Wiley
• Subjects: active suppression; Administration, Oral; Biological and medical sciences; Cell Proliferation - drug effects; chronic allograft nephropathy; Chronic Disease; epitope spreading; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - immunology; Graft Rejection - prevention & control; HLA-DR2 Antigen - immunology; Humans; indirect allorecognition; kidney transplantation; Kidney Transplantation - immunology; Kidney Transplantation - pathology; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; oral tolerance; Peptide Fragments - administration & dosage; Pilot Projects; Renal failure; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tissue Donors; Tissue, organ and graft immunology; Transplantation, Homologous; Suboptimal donor; active suppression; Chronic renal failure; Peptides; chronic allograft nephropathy; Suppression; Class II histocompatibility antigen; Homograft; Homotransplantation; Kidney; Complexity; Surgery; Graft; Human; Kidney disease; Urinary system disease; Oral administration; Tolerance; indirect allorecognition-kidney transplantation; Complexes; Medicine; Rejection; Chronic; Epitope spreading; Nephropathy; Treatment; Urinary system; oral tolerance; Renal failure; Kidney transplantation
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1111/j.1399-0012.2008.00871.x

:  Oral tolerance is an important physiological mechanism of immune hyporesponsiveness to dietary antigens and the commensal flora of the gastrointestinal tract. Feeding of alloantigens, therefore, has the potential to suppress undesirable immune responses after transplantation. To date, there are no published reports on the effects of such an approach in human transplant recipients. In the present pilot study, we demonstrate complete suppression of baseline indirect alloreactivity in patients with chronic renal allograft dysfunction following the oral feeding of low (0.5 mg/d) but not higher (1.0 and 5.0 mg/d) doses of donor major histocompatibility complex (MHC) class II peptides. The regimen was well tolerated with no evidence for sensitization to the donor antigen. Our results indicate that oral feeding of low dose donor MHC peptide may represent a safe and effective therapy to suppress indirect alloreactivity in renal transplant recipients with chronic allograft dysfunction and warrants further clinical investigation.