Anti-intercellular adhesion molecule-1 antibodies in sera of heart transplant recipients: a role in endothelial cell activation.
BACKGROUND
Antiendothelial antibodies to non-human leukocyte antigens are made by a subset of heart transplant recipients, but the specificity of such antibodies is undefined. Intercellular adhesion molecule (ICAM)-1 is an abundantly expressed adhesion molecule with polymorphic residues, expressed on the surface of endothelial cells. The hypothesis that ICAM-1 acts as a minor histocompatibility antigen and that anti-ICAM-1 antibodies, directed against polymorphic residues, could be one component of the antiendothelial antibodies found after heart transplantation has been tested.


METHODS
Chinese hamster ovary cells were transfected with full-length polymorphic variants of human ICAM-1. The binding of antibodies (immunoglobulin [Ig] G or IgM) to these cells was measured using sera from 50 heart transplant recipients (pretransplant and 1 and 2 years posttransplant) and sera from 20 normal volunteers by flow cytometry. The recipients and donors were genotyped for ICAM-1 polymorphisms.


RESULTS
Sixty-eight percent (n=34) of patients made IgM antibodies that bound to ICAM-1. However, it seems unlikely that ICAM-1 is a minor transplantation antigen, because there were no differences in antibody production from recipients matched or mismatched for ICAM-1 alleles. The antibodies bound to mouse endothelial cells that were engineered to overexpress human ICAM-1, and induced a robust activation of the Erk-2 mitogen-activated protein kinase pathway.


CONCLUSIONS
Anti-ICAM-1 antibodies are produced after cardiac transplantation, but not to polymorphic residues. Such antibodies may contribute to the endothelial activation by binding to the endothelium, causing activation of proinflammatory signaling pathways.
Lawson
Charlotte
C
Transplant Immunology Group, Imperial College, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, United Kingdom. chlawson@rvc.ac.uk
Holder
Angela L
AL
Stanford
Rachel E
RE
Smith
John
J
Rose
Marlene L
ML
D000328:Adult; D000818:Animals; D000917:Antibody Formation; D001379:Azathioprine / Q000627:therapeutic use; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006331:Heart Diseases / Q000145:classification / Q000601:surgery; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
D017931:DNA Primers; D007166:Immunosuppressive Agents; D018799:Intercellular Adhesion Molecule-1; D009173:Mycophenolic Acid; D001379:Azathioprine