DEVELOPMENT OF ELISA-DETECTED ANTI-HLA ANTIBODIES PRECEDES THE DEVELOPMENT OF BRONCHIOLITIS OBLITERANS SYNDROME AND …

A Jaramillo, MA Smith, D Phelan, S Sundaresan… - …, 1999 - journals.lww.com
A Jaramillo, MA Smith, D Phelan, S Sundaresan, EP Trulock, JP Lynch, JD Cooper…
Transplantation, 1999journals.lww.com
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 …
Abstract
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.
Lippincott Williams & Wilkins