P134 Fast de novo donor specific antibody development in lung transplant recipient

Abstract

Aim Donor specific antibodies (DSA) represent the major obstacle in solid organ transplantation. The aim of this study was to analyze the reasons of fast (10 days) development of strong DSA in the recipient after single lung transplantation. Methods A 66-yo female patient (typed B∗39:01, 44:02) underwent single lung transplant (typed B∗81:01, 15:17) on 02/07/2016 with negative DSA and flow cytometry cross match (FC XM). Historical samples did not have any DSA and were FC XM negative. On 02/17/2016 strong DSA to B81 were detected. The rest of antibodies (Ab) were against different HLA-B specificities. Ab analysis was performed using single antigen bead assay. Epitope (E) analysis of mismatched (MM) antigens (Ag) was conducted by using HLAMatchmaker computer algorithm. Three-color assay was used for FC XM. Results Ab reactivity, Ag E analysis and sensitizing events are presented in Table 1. Interest deserves chronology of sensitizing events recipient had been exposed to during her live. She has two children who were born in 1981 (typed B∗07:02, 44:02) and 1983 (typed B∗27:03, 39:01). The patient received pneumococcal (P) and shingle vaccinations in 08/2008 and 09/2009, respectively. In 10/2014 the patient received P vaccination followed by two Hepatitis A and B vaccinations (09/2015 and 10/2015), Tdap (09/2015), Flu and MMR (10/2015). Hepatitis A, shingle and MMR vaccines contain viruses grown on live human lung fibroblasts (HLF) (MRC-5, typed B∗07:02, 44:02, and WI-38, typed B∗08:01, 58:01). Each dose of vaccine used for injection is known to contain protein components of HLF including HLA. Detailed analysis of reactive E of B locus Ag recipient developed Ab to, MM E of the children and MRC-5 HLF revealed shared pattern which included single and pared E. Conclusions Most likely fast de novo DSA development is due to immunological memory booster effect produced by five exposures to MM B locus alleles which share the following Es: 70IAQ, 65QIA, 65QIA+76esn, 69aa+80n, and 163ew+73te. The later three consist of paired non-self and self Es Download : Download high-res image (965KB) Download : Download full-size image