SIGNIFICANCE OF PREFORMED CLASS II ANTIBODIES IN LUNG TRANSPLANT RECIPIENTS.
JC Scornik, M Baz, WH Donnelly, ED Staples. University of Florida
College of Medicine, Gainesville, Florida.
Susceptibility to graft damage by preformed antibodies
(Abs) can be high for some organs (kidney) and low for others (liver).
There is limited evidence that lung transplants (txp) have a high susceptibility
for preformed Class I HLA Abs, but because of a low rate of sensitization
in these patients only fragmented information is available. We report here
the association of a hyperacute lung rejection with a clear Class II Ab
and our experience with 83 consecutive lung txp. The crossmatch, performed
by flow cytometry in all patients, was positive in 6 (7%); all of them
in adult females. Low-level (flow positive, cytotoxicity negative) Class
I Abs were detected on T and B cells in 4 patients. One developed severe
but reversible pulmonary edema and hypoxemia, undistinguishable from reperfusion
injury, and 3 had a benign course. In contrast, 2 patients had B cell Abs
(flow positive, cytotoxicity negative), and both had serious pulmonary
edema and hypoxemia. One patient recovered but the other died 2 days post-txp.
At autopsy her lungs had diffuse intra alveolar hemorrhage, diffuse capillaritis
(PMNs and lymphocytes), hyaline membranes, and fibrin/platelet thrombi
in pulmonary veins. Immunostaining was positive for IgG, IgA, IgM and C3;
HLA-DR was strongly expressed in endothelial and alveolar cells. Ab analysis
by flow cytometry with a 12-cell panel showed positive results with B cells
from 5 DR11+ cells and negative with 7 DR11 negative cells (p<0.001,
Fisher exact test). DR11 was present in the donor but not in the recipient.
Since normal donor lungs, as the one hyperacutely rejected, express DR
in endothelial and alveolar cells, these results suggest for the first
time that DR Abs, even at low concentrations, may, alone or in conjunction
with reperfusion injury, lead to serious damage of lung allografts.