Anti-human leukocyte antigen antibodies and preemptive antibody-directed therapy after lung transplantation.
BACKGROUND
Because the development of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) after lung transplantation has been associated with acute and chronic rejection, we implemented a clinical protocol to screen all transplant recipients for DSA and preemptively treat those who developed DSA with rituximab and intravenous immune globulin (IVIG), or IVIG alone.


METHODS
We conducted a prospective observational study of this protocol and used the LABScreen Single Antigen assay to detect DSA after transplantation. We compared the incidence of acute rejection, lymphocytic bronchiolitis, and bronchiolitis obliterans syndrome (BOS) between those who developed DSA and those who did not using Cox proportional hazards models. We used the Kaplan-Meier method to compare freedom from BOS and survival between those who had persistent DSA and those who had successful depletion of DSA.


RESULTS
Among 116 recipients screened, DSA developed in 65 during the study period. Those who developed DSA and received antibody-directed therapy had a similar incidence of acute rejection, lymphocytic bronchiolitis, and BOS as those who did not develop DSA. Furthermore, recipients who had successful depletion of DSA had greater freedom from BOS and better survival than those who had persistent DSA. Finally, those treated for DSA had a similar incidence of infectious complications as those who did not develop DSA.


CONCLUSIONS
The development of DSA is surprisingly common after lung transplantation. Antibody-directed therapy may reduce the risk of rejection associated with DSA, but a randomized controlled trial is necessary to critically evaluate the efficacy of this treatment protocol.
Hachem
Ramsey R
RR
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Rhachem@dom.wustl.edu
Yusen
Roger D
RD
Meyers
Bryan F
BF
Aloush
Aviva A
AA
Mohanakumar
Thalachallour
T
Patterson
G Alexander
GA
Trulock
Elbert P
EP
D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood*; D000077552:Basiliximab; D001988:Bronchiolitis / Q000276:immunology; D001989:Bronchiolitis Obliterans / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D006736:Horses; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D055815:Young Adult
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D001323:Autoantibodies; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab