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HA-1 mismatch has significant effect in chronic allograft nephropathy in clinical renal transplantation

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Krishnan, N. S., Higgins, Rob, Lam, F. T., Kashi, H., Jobson, S., Ramaiyan, K., Rahman, M. and Morris, A. G. (Alan George) (2007) HA-1 mismatch has significant effect in chronic allograft nephropathy in clinical renal transplantation. Transplantation Proceedings, Vol.39 (No.5). pp. 1439-1445. doi:10.1016/j.transproceed.2007.02.066

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Official URL: http://dx.doi.org/10.1016/j.transproceed.2007.02.0...

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Abstract

Background. The minor histocompatibility antigen HA-1 occurs in two allelic forms: H and R. The HA-1(H) 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-1(H)-specific tetramer reagent, and analyzed by flow cytometry. Controls were unstimulated cells; PBML from two patients never exposed to HA-1(H); 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.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RD Surgery
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Journal or Publication Title: Transplantation Proceedings
Publisher: Elsevier Inc.
ISSN: 0041-1345
Official Date: June 2007
Dates:
DateEvent
June 2007Published
Volume: Vol.39
Number: No.5
Number of Pages: 7
Page Range: pp. 1439-1445
DOI: 10.1016/j.transproceed.2007.02.066
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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