HA-1 Mismatch Has Significant Effect in Chronic Allograft Nephropathy in Clinical Renal Transplantation

Abstract Background The minor histocompatibility antigen HA-1 occurs in two allelic forms: H and R. The HA-1H form presented in the context of HLA A2 can elicit specific cytotoxic lymphocyte (CTL) responses and can cause graft-versus-host disease in marrow transplants. However, its significance in s...

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Published in:	Transplantation proceedings Vol. 39; no. 5; pp. 1439 - 1445
Main Authors:	Krishnan, N.S, Higgins, R.M, Lam, F.T, Kashi, H, Jobson, S, Ramaiyan, K, Rahman, M, Morris, A
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-06-2007 Elsevier Science
Subjects:	Adult Aged Biological and medical sciences Chronic Disease Female Fundamental and applied biological sciences. Psychology Fundamental immunology Graft Rejection - epidemiology Graft Rejection - immunology Histocompatibility Testing HLA-A2 Antigen - immunology Humans Kidney Transplantation - adverse effects Kidney Transplantation - immunology Kidney Transplantation - mortality Lymphocyte Culture Test, Mixed Male Medical sciences Middle Aged Minor Histocompatibility Antigens - immunology Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Oligopeptides - immunology Postoperative Complications - immunology Renal failure Surgery Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system Survival Analysis Tissue, organ and graft immunology Transplantation Chimera Incompatibility Kidney disease Urinary system disease Homograft Homotransplantation Medicine Rejection Chronic Nephropathy Treatment Surgery Renal failure Graft Kidney transplantation
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Summary:	Abstract Background The minor histocompatibility antigen HA-1 occurs in two allelic forms: H and R. The HA-1H form presented in the context of HLA A2 can elicit specific cytotoxic lymphocyte (CTL) responses and can cause graft-versus-host disease in marrow transplants. However, its significance in solid organ transplants is unknown. We determined whether incompatibility of the HA-1 resulted in enhanced rejection and whether HA-1 specific CTLs were generated. Materials and methods HLA A2-matched donor/recipient pairs were selected and typed for HA-1 antigens by polymerase chain reaction. Nineteen of 81 pairs were mismatched for HA-1. Peripheral blood mononuclear leucocytes from five recipients, HLA A2 DR-matched with donors, were stimulated for 3 days with third-party donor, matched for HLA A2 DR but mismatched for HA-1. Cells were stained for surface markers, HA-1H -specific tetramer reagent, and analyzed by flow cytometry. Controls were unstimulated cells; PBML from two patients never exposed to HA-1H ; immunoglobulin G isotype-matched controls. For all patients, acute rejection rates posttransplant was ascertained. Long-term data was available for 36 patients. Results and conclusions There was no difference in acute rejection rates between the HA-1-matched and -mismatched groups, but there was a significant difference in chronic rejection rates, evidenced by increased graft failures during the follow-up period ( P = .0024). Lymphocytes from five HA-1-mismatched recipients were stimulated in vitro with cells from HLA-A2 and DR-matched but HA-1-mismatched surrogate donor. Though there seemed to be an excess of tetramer-positive cells, anti-HA-1-specific CTL responses were not conclusively elicited in vitro.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-1345 1873-2623
DOI:	10.1016/j.transproceed.2007.02.066