Identification of non-HLA target antigens recognized after lung transplantation.

Background: It has become evident that, besides cellular allogeneic immune responses against airway epithelial cells (AEC), humoral responses also contribute significantly to the pathogenesis of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Antibody responses against transplanted lungs are directed against HLA and non-HLA antigens, but the identity of the latter antigens is presently unknown.

Methods: The main purpose of this study is to identify non-HLA target antigens on donor lungs recognized by patients' antibodies after LTx. Serum samples were taken before and 6 months after lung transplantation from 11 patients (4 men and 6 women, median age 44 years, range 18 to 63 years). Protein expression libraries were made from the luminal side containing AEC of discarded the donor bronchus, which was snap frozen in liquid N(2) during the organ harvesting procedure. Subsequently, all sera were analyzed for reactivity against library-encoded antigens by serologic analysis of recombinant cDNA expression libraries (SEREX). Recognized gene products were sequenced and analyzed by the NCBI/BLAST server.

Results: From a total of +/-3 x 10(4) gene products analyzed, six different non-HLA antigens were recognized by individual patient sera. Gene analysis indicated that they consisted of both polymorphic (PSMC4, F3, LOC284058, PLUNC, ZNF33A) and non-polymorphic (XP_931864) antigens. Cross-sectional analysis indicated that some antigens were recognized by 4 of 10 patient sera tested.

Conclusions: Antibodies directed against non-HLA antigens are present after LTx, and can be identified using the SEREX technique. Identification of target antigens recognized after LTx will improve our understanding of the pathogenesis of BOS. Monitoring of the antibody response may be used to predict BOS.