Meeting report: 3rd international transplant conference: how much risk can you take? D. Lowe * , S. Daga †,‡ , D. Briggs § , N. Khovanova ¶ , D. Mitchell † , R. Higgins ‡ & N. Krishnan ‡ Summary The 3rd International Transplant Conference took place on 31st October and 1st November 2014 at the University of Warwick, Coventry, UK. Key focal points of the meeting were the exploration of the molecular basis of antibody–antigen interactions and their relation to clinical practice and to share experi- ences and knowledge regarding strategies to transplant the ‘high-risk’ patient. In addition, lively debate ses- sions were hosted where controversial clinical and immunological themes were discussed by leading experts in the field. Introduction The growing disparity between the number of patients presenting with renal failure necessitating transplanta- tion and the availability of donor organs has led to concerted efforts to increase the rates of live donor transplantation. Given that over 30% of patients awaiting transplantation in the UK are now sensitized against HLA antigens, it has increasingly become stan- dard practice to transplant against both HLA and ABO antibody barriers. As outlined in the previous meeting back in 2012, the sharing of knowledge and clinical procedures in these high-risk cases is key to successful management and prolonged graft survival (Lowe et al., 2013). This meeting explored the factors that contribute to HLA immunogenicity and the factors that influence the pathogenicity of donor-specific antibody responses. Following on from the previous meeting in 2012 which comprehensively reviewed the prevalence and importance of transplant infectious disease, the meet- ing this time focussed on clinical risk management in renal transplantation, pinpointing not just the trans- plant recipient but also on factors which impact on donor assessment and selection. Antibody-Mediated Rejection (AMR) and aspects of antibody–antigen interactions: 31st October 2014 Professor Rob Higgins set the scene by summarizing key issues around antibody-incompatible kidney trans- plantation (AiT) from a UK perspective. He high- lighted difficulties in diagnosing antibody-mediated damage to the allograft with current technologies. He noted that conventional immunohistochemistry often does not demonstrate antibody in biopsy material, even during acute antibody-mediated rejection. Anti- body is presumably present, as indicated by studies eluting donor-specific HLA antibodies from graft biop- sies (Martin et al., 2003). Similarly, complement bind- ing and activation may not be universal during acute antibody-mediated rejection and hence the recent down-grading of C4d-positive staining in the latest Banff criteria (Haas et al., 2014). A key marker of AMR is usually high cellular infiltration and staining for CD45 (expressed at high levels on nucleated hema- topoietic cells) observed early, combined with CD68 & CD3 staining for mononuclear cells and T cells that are positive during AMR (Higgins et al., 2010). Graft outcome is linked to the level of antibodies, and posi- tive complement-dependant cytotoxicity (CDC) cross- match prior to transplant was particularly associated with diminished graft function at 10 years (in the Cov- entry series, <50% death censored graft survival for CDC positive compared to 84% with CDC negative cross-match). Of 29 cases that were CDC-positive pre- treatment, six were CDC positive at time of transplant and only one had primary nonfunction due to hyper- acute AMR with the remaining five cases functioning well at up to 10 years post-transplant. All of these five cases had donor-specific antibodies (DSAs) mainly *Transplant Immunology, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK, † Clinical Sciences Research Laboratories, University of Warwick, Coventry, UK, ‡ Renal Department, University Hospital Coventry and Warwickshire, Coventry, UK, § Department of Histocompatibility and Immunogenetics, NHS Blood and Transplant, Birmingham, UK and ¶ School of Engineering, University of Warwick, Coventry, UK Received 12 December 2014; revised 9 January 2015; accepted 27 January 2015 Correspondence: Dave Lowe, Transplant Immunology Department, Royal Liverpool and Broadgreen University Hospital, L7 8XP Liver- pool, UK. Tel: 0151 706 4366; Fax: 0151 706 5814; E-mail: david.lowe@rlbuht.nhs.uk © 2015 John Wiley & Sons Ltd International Journal of Immunogenetics, 2015, 0,1–10 1 doi: 10.1111/iji.12184