High incidence of donor-reactive delayed-type hypersensitivity reactivity in transplant patients.
Evidence of transplant recipient cellular sensitization towards donor antigens has rarely been directly measured. Rather, sensitization has been generally inferred by the presence of detectable allo-reactive or donor-reactive antibodies. In this study a newly developed delayed-type hypersensitivity assay was used to directly determine the incidence of post-transplant donor-reactive T-cell sensitization in a large cohort of kidney and simultaneous kidney-pancreas recipients. These results were compared with the presence of detectable circulating alloantibodies and with patient clinical outcome. We found an unexpectedly high incidence (52%) of donor-reactive delayed-type hypersensitivity reactivity in our study patients. Donor-reactive delayed-type hypersensitivity reactivity occurred at a much higher frequency than detectable alloantibodies (20%). Further, we found no correlation between the presence of alloantibodies and donor-reactive delayed-type hypersensitivity reactivity. We also found no correlation between the development of donor-reactive delayed-type hypersensitivity reactivity and the degree of donor and recipient HLA matching. Finally, the presence of detectable donor-reactive delayed-type hypersensitivity reactivity did not correlate with a worse clinical outcome at the time of these analyses. We conclude that in transplant recipients, the presence of circulating alloantibodies is a poor indicator of previous T-cell sensitization to donor antigens. We also conclude that our current immunosuppression strategies are relatively ineffective at blocking T-cell allosensitization, but are very effective at blocking the biological consequences of that allosensitization.
Pelletier
Ronald P
RP
The Ohio State University College of Medicine and Public Health, Department of Surgery, Columbus, Ohio 43210, USA. pelletier-1@medctr.osu.edu
Hennessy
Patrice K
PK
Adams
Patrick W
PW
Orosz
Charles G
CG
D000208:Acute Disease; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006650:Histocompatibility Testing; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000453:epidemiology* / Q000209:etiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D016035:Pancreas Transplantation / Q000009:adverse effects / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology*; D044469:Racial Groups; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D014481:United States
D007166:Immunosuppressive Agents; D007518:Isoantibodies