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.
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada. pgrimm@ucsd.edu
P C
PC
Grimm
R
R
McKenna
P
P
Nickerson
M E
ME
Russell
J
J
Gough
E
E
Gospodarek
B
B
Liu
J
J
Jeffery
D N
DN
Rush
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