Susceptibility of lung transplants to preformed donor-specific HLA antibodies as detected by flow cytometry.
BACKGROUND
Preformed anti-HLA antibodies are known to have the potential to induce early graft damage in organ transplant recipients. However, in lung transplant recipients, little information exists about the significance of preformed antibodies directed to either class I or class II HLA antigens.


METHODS
A two-color flow cytometry cross-match was performed in 92 consecutive lung transplant recipients using serum obtained immediately before transplantation. The presence of preformed antibodies was correlated with the incidence of severe graft dysfunction manifested as pulmonary infiltrates and severe hypoxemia with onset in the first few hours after transplantation.


RESULTS
Six patients (6.5%) had low-level anti-donor IgG antibodies detected by flow cytometry, four against T and two against B lymphocytes. Three patients (50%) developed severe graft dysfunction with pulmonary infiltrates and hypoxemia. Two patients responded to treatment, but the third, who had an antibody highly specific for HLA-DR11, died at 48 hr after transplant. Results of histopathologic studies in this patient are consistent with hyperacute rejection and support a pathogenic role of these antibodies. In contrast, of 86 (93.5%) cases with a negative flow cytometry cross-match, only 4 (5%) had severe but reversible early graft dysfunction with pulmonary infiltrates and hypoxemia, attributed to ischemia-reperfusion injury (P<0.005).


CONCLUSIONS
Class II, and perhaps class I HLA antibodies at relatively low concentrations represent a risk factor for severe early pulmonary graft dysfunction, with the potential to progress to hyperacute rejection and death.
Scornik
J C
JC
Department of Pathology, University of Florida College of Medicine, Gainesville 32610, USA.
Zander
D S
DS
Baz
M A
MA
Donnelly
W H
WH
Staples
E D
ED
D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006684:HLA-DR Antigens / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D012189:Retrospective Studies
D000888:Antibodies, Anti-Idiotypic; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D007074:Immunoglobulin G