Clinical rejection is distinguished from subclinical rejection by increased infiltration by a population of activated macrophages.
It has been reported previously that one-third of protocol renal biopsies in asymptomatic, biochemically stable renal transplant recipients in the first 6 mo show unsuspected subclinical graft rejection (both infiltrate and tubulitis) and that subclinical rejection is a risk factor for chronic renal dysfunction. This study was performed to determine whether differences in phenotype or activation status of graft-infiltrating cells underlie these different manifestations of acute rejection. Biopsies with normal histology (n = 10), subclinical rejection (n = 13), and clinical rejection (n = 9) were studied using immunohistochemistry and computerized image analysis. Subclinical and clinical rejections had similar histologic Banff scores. Univariate analysis showed a trend for a higher infiltration with CD8+ (P = 0.053) and CD68+(P = 0.06) cells in clinical rejection. Of the activation markers studied (CD25, perforin, tumor necrosis factor-alpha), only allograft inflammatory factor-1+-activated macrophages were significantly (P = 0.014) increased in the infiltrate of clinical rejection biopsies. These data suggest that activated macrophages or their products are responsible for acute renal dysfunction associated with clinical rejection episodes.
Grimm
P C
PC
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada. pgrimm@ucsd.edu
McKenna
R
R
Nickerson
P
P
Russell
M E
ME
Gough
J
J
Gospodarek
E
E
Liu
B
B
Jeffery
J
J
Rush
D N
DN
D000208:Acute Disease; D015703:Antigens, CD / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins; D010641:Phenotype
C112986:AIF1 protein, human; D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins