Role of beta3 integrin in acute renal allograft rejection in humans.
OBJECTIVE
Beta3 Integrin may play a role in the process of acute rejection by increasing leukocyte adhesion to the endothelium, cytotoxic T lymphocyte activation, and platelet aggregation.


METHODS
For investigation of the role of beta3 integrin in the pathogenesis of acute rejection, this study examined the surface expression of beta3 integrin on leukocyte subsets and analyzed a common single-nucleotide polymorphism in exon 2 of the gene encoding the beta3 subunit that generates two beta3 integrin isoforms, termed Pl(A1) and Pl(A2). Pl(A) genotype was determined in blood samples from 445 renal allograft recipients at two centers. Patients were then grouped by Pl(A) genotype, and clinical outcomes as recorded in a preexisting database were analyzed.


RESULTS
Although almost all monocytes express beta3 integrin, its expression was also found on all leukocyte subsets, including T, B, and NK cells. The percentage of patients who experienced acute rejection was noted to be significantly higher in those with Pl(A1)/Pl(A1) (TT) genotype versus patients with the Pl(A1)/Pl(A2) or Pl(A2)/Pl(A2) (CT or CC) genotypes (33% for TT versus 20% for CT or CC). In a multivariate analysis, the Pl(A1)/Pl(A1) (TT) genotype remained significantly associated with acute rejection. Patients with Pl(A1)/Pl(A1) (TT) genotype also exhibited a higher number of acute rejection episodes per patient.


CONCLUSIONS
The Pl(A1)/Pl(A1) (TT) genotype is associated with an increased incidence of acute renal allograft rejection in humans, supporting a role for beta3 integrin in the pathophysiology of acute rejection.
Chandrakantan
Arun
A
Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
McDermott
David H
DH
Tran
Huong Thi Bich
HT
Jurewicz
Mollie
M
Gallon
Lorenzo
L
Gaston
Robert
R
Milford
Edgar
E
Abdi
Reza
R
D000208:Acute Disease; D000328:Adult; D000368:Aged; D044383:Black People; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D039661:Integrin beta3 / Q000097:blood / Q000235:genetics / Q000502:physiology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014184:Transplantation, Homologous; D044465:White People
D039661:Integrin beta3