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


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.


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.
Krishnan
N S
NS
Renal Unit, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry, England, UK. nithyaskrishnan@yahoo.co.uk
Higgins
R M
RM
Lam
F T
FT
Kashi
H
H
Jobson
S
S
Ramaiyan
K
K
Rahman
M
M
Morris
A
A
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology*; D011183:Postoperative Complications / Q000276:immunology*; D016019:Survival Analysis; D018183:Transplantation Chimera
C110615:HA-1 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides