Alloreactivity in renal transplant recipients with and without chronic allograft nephropathy.
The pathogenesis of chronic allograft nephropathy (CAN) involves both immunologic (antigen-dependent) and nonimmunologic (antigen-independent) mechanisms. In order to provide further insight into the immunologic basis of this disease, a cross-sectional analysis of cellular and humoral immunity in human renal allograft recipients with or without deteriorating renal function and biopsy proven CAN was performed. Interferon-gamma enzyme-linked immunosorbent spot assays were used to assess cellular immunity to donor, or fully mismatched third-party stimulator cells (direct pathway), and to synthetic peptides derived from donor HLA molecules (indirect pathway). Anti-HLA antibodies were evaluated by flow cytometry using HLA-coated beads. Both the mean frequencies of donor-reactive peripheral blood lymphocytes and the number of individuals who responded to donor antigens per group were statistically higher in CAN patients versus control subjects (P < 0.02). Calculated ratios of donor/third-party enzyme-linked immunosorbent spot responses showed mean values of 2.61 +/- 3.0 in the CAN group, with ratios of 0.50 to 0.72 +/- 0.42 in control subjects (P < 0.001), confirming that direct, donor-specific cellular immunity predominated in patients with CAN. Fifty percent of CAN patients studied exhibited donor peptide reactivity compared with only 28.6% in control subjects. Finally, 33% of patients in the CAN group developed new posttransplantation anti-HLA antibodies compared with only 4% in the control group (P < 0.05). Overall, the results suggest that persistent cell-mediated and humoral alloimmunity contribute to the development of CAN and further demonstrate that anti-donor immunity in patients with CAN is heterogeneous. Immune monitoring to predict long-term outcome should include multiple measures of cellular and humoral immunity.
Poggio
Emilio D
ED
Department of Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Clemente
Michael
M
Riley
Jocelyn
J
Roddy
Meagan
M
Greenspan
Neil S
NS
Dejelo
Cora
C
Najafian
Nader
N
Sayegh
Mohamed H
MH
Hricik
Donald E
DE
Heeger
Peter S
PS
D000328:Adult; D000483:Alleles; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection; D006680:HLA Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007107:Immune System; D007109:Immunity; D007371:Interferon-gamma / Q000378:metabolism; D007674:Kidney Diseases / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000473:pathology*; D010455:Peptides / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism
D006680:HLA Antigens; D010455:Peptides; D007371:Interferon-gamma