NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibody-mediated rejection.
To explore the mechanisms of antibody-mediated rejection (ABMR) in kidney transplants, we studied the transcripts expressed in clinically indicated biopsies from patients with donor-specific antibody (DSA). Comparison of biopsies from DSA-positive versus DSA-negative patients revealed 132 differentially expressed transcripts: all were associated with class II DSA but none with class I DSA. Many transcripts were expressed in DSA-positive ABMR but were also expressed in T-cell-mediated rejection (TCMR), reflecting shared molecular features. Removal of shared transcripts created 23 DSA selective transcripts (DSASTs). Some DSASTs (6/23) showed selective high expression in NK cells, whereas others (8/23) were expressed in endothelium or in endothelium plus other cell types (7/23). Of 145 biopsies ranked by DSAST expression, the 25 with highest DSAST expression primarily consisted of ABMR (22/25, 88%), either C4d-positive or C4d-negative. By immunostaining, CD56+ and CD68+ cells in peritubular capillaries, but not CD3+ cells, were increased in ABMR compared to TCMR, compatible with a role for NK cells, as well as macrophages, as effectors in endothelial injury during ABMR. Thus, the strategy of using DSASTs in the biopsy to identify mechanism-related transcripts in biopsies from patients with clinical phenotypes indicates the selective involvement of NK cells in ABMR.
Hidalgo
L G
LG
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
Sis
B
B
Sellares
J
J
Campbell
P M
PM
Mengel
M
M
Einecke
G
G
Chang
J
J
Halloran
P F
PF
D000465:Algorithms; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001706:Biopsy; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015935:Complement C4b / Q000032:analysis; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D000097382:CD68 Molecule
D000906:Antibodies; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D019002:CD56 Antigen; D015935:Complement C4b; D010446:Peptide Fragments; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C032261:complement C4d