Abstract

Purpose The significance of donor-specific HLA antibodies (DSA) in lung transplantation (LTx) has emerged with the introduction of solid phase assays for antibody detection. Using ELISA based screening we have shown that 14% of LTx had de novo DSA and most (78%) developed chronic allograft rejection vs. 24% in patients without DSA. Further evaluation of DSA with Luminex (L) based methods for screening, specificity and functional analysis is needed to determine the impact of pre-formed and de-novo DSA on outcome. Methods and Materials Patients who were transplanted January 2011 to July 2012 and were screened prospectively for DSA with L-PRA were included in the analysis. The screening included samples pre-Tx and post LTx at 1 month and every 2 months in conjunction with surveillance and clinical bronchoscopies. The specificity of DSA and strengths (MFI) determined with single antigen beads (L-IgG) and complement binding with L-C1q- assay (L-C1q) was associated with cellular rejection and antibody mediated rejection. Results This study was done on 149 consecutive LTx with a minimum follow-up of 3 months and adequate DSA screening. All had negative CDC T and B cell crossmatches. 5% had DSA pre-Tx that persisted post-Tx and 23% had de-novo DSA within 3-6 months post LTx. Overall, 55% of LTx had high grade ACR; de-novo DSA was higher in ACR (22/82, 27%) vs. no ACR (5/67, 7%) (p 70%) de-novo DSA were HLA-DQ specific including Ab towards DQB, DQA and combination of DQB/DQA pairs. Severe ACR (n=4) with DSA and C1q reactivity was treated with plasmapheresis, IVIG and Rituximab for AMR. Patients with ACR and low level or declining DSA that had a transient or no C1q reactivity (n=19) were not treated for AMR. DSA in LTx without ACR were also low level, transient and without C1q reactivity. Conclusions The frequency of de-novo DSA is higher than previously reported. Persistent, high grade ACR with C1q binding class II HLA-DQ DSA was associated with AMR.

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