Expression of MHC class I-related Chain B (MICB) molecules on renal transplant biopsies.
BACKGROUND
MICA and MICB (MHC class I-related chain A and B) are polymorphic genes that encode molecules related to MHC class I and are expressed on epithelial cells in response to stress. Incompatible donor MIC antigens can stimulate antibody production in transplant recipients. This study was designed to determine MICB expression in kidney pretransplant and any subsequent changes in expression following transplantation and to correlate changes with inflammatory markers and clinical events.


METHODS
Paired renal biopsies obtained from living donor (n=10) and cadaveric allografts (n=50) before and 7 days posttransplant were stained for MICB, leukocytic infiltration, and HLA class II antigens.


RESULTS
Variable tubular MICB expression was evident in donor biopsies [high 6/60 (10%), low/negative 13/60 (22%), intermediate 41/60 (68%)]. Following transplantation, MICB was up-regulated on renal tubules of 17/60 (28%) biopsies and was associated with MHC class II antigen induction (P=0.02) and leukocyte infiltration (P=0.01). Acute tubular necrosis leading to delayed graft function (DGF) and acute rejection (AR) cause cellular stress within the transplanted kidney. We found a strong association between up-regulation of MICB and cellular stress, 15/17 biopsies with up-regulated MICB expression had AR and/or DGF (P=0.003).


CONCLUSIONS
This is the first study demonstrating variable levels of MICB expression in kidneys before transplantation and induction of MICB expression following renal transplantation. MICB expression is associated with HLA class II antigen induction, leukocytic infiltration of the graft and cellular stress in the transplanted kidney. Expression of MICB could contribute significantly to the alloimmune response in mismatched donors and recipients.
Quiroga
Isabel
I
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Salio
Mariolina
M
Koo
Dicken D H
DD
Cerundolo
Lucy
L
Shepherd
Dawn
D
Cerundolo
Vincenzo
V
Fuggle
Susan V
SV
D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001706:Biopsy; D003106:Colon / Q000737:chemistry; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry* / Q000473:pathology; D016030:Kidney Transplantation; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C098080:MICB antigen