Abstract
Aim Elevated %ddcfDNA levels have been shown to correlate with allograft injury and acute rejection in lung transplantation. This case highlights how conventional post-transplant monitoring may underestimate the complex interactions between infection, injury, and de novo donor specific antibody (DSA) development. Methods Quantitation of %ddcfDNA via next generation sequencing was performed as part of the Genomic Research Alliance for Transplantation (GRAfT) consortium. DSA monitoring utilized Luminex phenotype and single bead immunoassays. Spirometry was used to assess pulmonary function and transbronchial biopsies to assess rejection. Bronchoalveolar lavage, blood samples and sputum cultures were used to diagnose infections. Results A 60 year old male with interstitial lung disease received a single lobe lung transplant. This patient was entered into GRAfT, a blinded prospective trial to investigate the use of %ddcfDNA to monitor allograft injury and predict long term outcomes. Immediately after transplant, high %ddcfDNA was detected in the recipient’s plasma which declined over several weeks. A biopsy on post-operative day (POD) 192 indicated mild acute cellular rejection concomitant with an infection and a spike in %ddcfDNA. The elevated %ddcfDNA ( > 1% threshold) suggested substantial injury to the allograft despite stable lung function. The patient experienced several infections prior to the detection of HLA-DQB1 de novo DSA. The second %ddcfDNA spike was concurrent with an increase in DSA and loss in lung function. Therapeutic plasma exchange reduced DSA with corresponding %ddcfDNA regression and improved lung function. An infection on POD 338 correlated with a third %ddcfDNA spike (last available measurement). The patient experienced further infections with a diminishing trend in lung function. Conclusion %ddcfDNA monitoring to detect cumulative clinical and subclinical injury may aid in assessing de novo DSA risk and in the development of interventions to prevent chronic allograft loss. Download : Download high-res image (141KB) Download : Download full-size image A.M. Jackson: 3. Speaker’s Bureau; Company/Organization; Thermo Fisher Scientific. DRB4*01:03:01 DQA1*03:01:01 DQB1*03:02:01 DPA1*01:03:01 DPB1*04:02:01 (HF = 0.03). A new DPA1*02:07:01_5407G > A was found. Conclusions As we published previously, the DRB1*04-DQA1*03-DQB1*03 association is strong but it is shown for the first time, that A*, B*, C* DQA1* and DPB1* alleles of Mexican AMI ancestry are strongly associated. The genetics of VKH is undoubtedly of Oriental origin, and present therefore in AMI, admixed groups such as Hispanics, Mediterranean and Asians. The shared epitope at S57-LLEQRRAA 67-74 in DR β 1 chain and the new class I associations are the basis to look for immunological intervention to block the T-cell response vs. the antigens that trigger the autoimmune response in VKH.
Published Version
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