Antibody-mediated rejection(AMR)is associated with both acute and chronic allograft dysfunction in LTRs. The clinical significance of HLA-II-DQ-DSA detection in organ transplantation had previously been controversial, but recently these antibodies have been associated with chronic rejection in the kidney. The significance of DQ-DSA in LTRs has not been examined. We report important clinical and histopathological consequences related to the presence of these antibodies in LTRs.
Single-center retrospective analysis of 50 LTRs who underwent a total of 58 transbronchial biopsies(TBBX) for surveillance or clinical deterioration and who had complete clinical and immunopathologic data available. A sensitive single antigen microarray technique was used to identify DSA before transplant and at time of TBBX. TBBX were reviewed for histologic changes and C4d-immunostaining.
No significant differences in demographics, immunosuppression, CMV status,ischemic time, or time to TBBX were found between LTRs with or without +HLA-DQ-DSA. +HLA-I and/or II was identified in 13/58 LTR. In 8/13, DQ-DSA was the only DSA identified. All eight TBBX were C4d- negative. Histology of 7/8 DQ-DSA+ TBBX showed fibrotic lesions with marked collagen deposition surrounding bronchovascular-dyads and/or interlobular-septae with severe vascular thickening of precapillary arterioles. These findings differed significantly from previously described lesions of AMR associated with +DSA/+C4d. 1/8 showed combined T-cell-rejection and bronchiolitis-obliterans. 8/8 showed progressive clinical deterioration.
Detection of HLA-II-DQ-DSA was associated with severe fibrotic allograft lesions and with progressive clinical deterioration without evidence of other causes. The low expression of DQ in lung tissue including activated endothelial cells may account for the absence of C4d-immunostaining in these TBBX.
Our findings provide the first evidence that DQ-DSA in LTRs has important clinical implications and may provide a prognostic indicator for poor graft survival. Moreover, it may be a useful marker in discriminating LTRs at greater risk for chronic graft dysfunction. +DQ-DSA could also identify an AMR component in cases of T-cell-mediated rejection. Prospective studies are needed to further evaluate the importance of surveillance and effective reduction of these antibodies on the outcomes of LTRs.
Deborah Levine, No Financial Disclosure Information; No Product/Research Disclosure Information