Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation.
BACKGROUND
Development of anti-HLA antibodies after lung transplantation (LT) is thought to play an important role in the etiology of bronchiolitis obliterans syndrome (BOS). However, a cause-effect relationship between anti-HLA antibodies and BOS has not been established. This study was conducted to determine the temporal relationship between the development of anti-HLA antibodies and BOS after LT, and to determine the antigenic specificity of the antibodies developed in BOS patients.


METHODS
Sera from 15 BOS+ LT patients and 12 BOS- LT patients were obtained before LT and collected again at 6, 12, 24, 36, and 48 months after LT. Anti-HLA antibodies were detected by the PRA-STAT ELISA system and by complement-dependent cytotoxicity assays. Anti-HLA reactivity was further characterized by flow cytometry and absorption/elution with human platelets.


RESULTS
When analyzed by ELISA, 10 of 15 BOS+ patients developed anti-HLA antibodies, whereas 0 of 12 BOS- patients developed anti-HLA antibodies (P<0.001). When analyzed by complement-dependent cytotoxicity, only 2 of 15 BOS+ patients developed anti-HLA antibodies and 1 of 12 BOS- patients developed anti-HLA antibodies (P = 0.99). There was a significant difference of 20.1 months between the time of anti-HLA antibody detection and the time of BOS diagnosis (P = 0.005). A progressive decrease in pulmonary function correlated with a progressive increase in the anti-HLA reactivity 36 months after LT. The anti-HLA reactivity was directed to one of the donor HLA class I antigens and to other unrelated HLA class I antigens. No anti-HLA reactivity was found against HLA class II molecules.


CONCLUSIONS
Our study indicates that anti-HLA class I antibodies play an important role in the pathogenesis of BOS and that monitoring of anti-HLA class I antibody development by a highly sensitive assay such as the PRA-STAT ELISA after LT can provide an early identification of an important subset of LT patients with an increased risk of developing BOS.
Jaramillo
A
A
Department of Surgery, HLA Laboratory, Barnes-Jewish Hospital, St. Louis, Missouri, USA.
Smith
M A
MA
Phelan
D
D
Sundaresan
S
S
Trulock
E P
EP
Lynch
J P
JP
Cooper
J D
JD
Patterson
G A
GA
Mohanakumar
T
T
D000906:Antibodies / Q000032:analysis* / Q000276:immunology; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D003165:Complement System Proteins / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D016040:Lung Transplantation; D011183:Postoperative Complications; D011184:Postoperative Period; D013997:Time Factors
D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D003165:Complement System Proteins