Deleterious effect of DQ donor specific antibody on chronic and acute rejection following lung transplant exacerbated by antibody to protein kinase C-[formula omitted

Abstract

Background HLA-DQ Donor Specific Antibody (DSA) is implicated in the negative impact of allograft function after lung transplantation. Non-HLA antibody to Protein Kinase C- ζ [(PKC- Z ) Ab] was reported to associate with graft injury in the absence of C4d deposition. Here we demonstrate DQ DSAs on chronic and acute graft injury elevated by (PKC- Z ) Ab following lung transplants. Case Report A 28-yo old male patient with cystic fibrosis underwent 1st Bilateral Lung Transplant (BLT) in 8/2011 with negative HLA DSA and cross-matches. Low titer (PKC- Z ) Ab was detectable. Graft function performed well in room air after BLT. In 9/2011 bronchoscopy biopsy showed A1B1 along with the appearance of DQ6 de novo DSA, but both biopsy and DSA turned negative following prednisone taper treatment. In 10/2014, he was admitted for cellular and antibody mediated rejection (CMR and AMR) with bronchoscopy biopsy A3B2R and significant increase of DQ6 without C4d deposition. At that time, (PKC- Z ) Ab was unchanged. One month later, (PKC- Z ) Ab abruptly increased to around 2.5-fold and DQ6 peaked (Fig. 1A1, A2). Patient lost allograft and received 2nd BLT on 11/19/2014 with negative cross-matches, DQ9 preformed DSA, and high titer (PKC- Z ) Ab. He was readmitted in 3/2015 for aggressive therapy for acute AMR with ×5 plasmapheresis, rituximab and bortezomib, and IVIG ×5 due to the significant drop of allograft function. AMR was aborted with remarkable decline of DQ9 DSA and (PKC- Z ) Ab on 4/21/2015 (Fig. 1B1, B2) resulting in improved graft function. Summary De novo DQ6 DSA with concurrent CMR resulted in chronic allograft rejection while preformed DQ9 DSA lead to acute allograft rejection after HLT. This negative impact of DQ DSAs to lung allograft injury and/or dysfunction was exacerbated by high titer (PKC- Z ) Ab. Download : Download full-size image