title: High incidence of donor-reactive delayed-type hypersensitivity reactivity in transplant patients.
abstract: 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.
authors.affiliation: The Ohio State University College of Medicine and Public Health, Department of Surgery, Columbus, Ohio 43210, USA. pelletier-1@medctr.osu.edu
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Pelletier
authors.forename: Patrice K
authors.initials: PK
authors.lastname: Hennessy
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Adams
authors.forename: Charles G
authors.initials: CG
authors.lastname: Orosz
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D007518:Isoantibodies