Hebrew University, Jerusalem, Israel
Laboratory Director, Northwestern University
(1) Understanding HLA immunogenicity: recent years have seen a flurry of publications using different software to assess “epitope matching” or more accurately, the degree of dissimilarity between donor and recipient HLA antigens (including HLA Matchmaker, PIRCHE II, etc,); thereby, confusing these molecular mismatches with epitopes. We have shown that not all mismatches have an equal immunogenic capacity and we are currently studying a unique cohort of patients (2MM1DSA; see AJT November 2019 publication) to better understand which of those mismatches are more detrimental to graft survival;
(2) Focus of HLA-DQ: my lab have been publishing in this field for over a decade, demonstrating the unique properties of the HLA-DQ molecules, the need to consider both the αβ chains, and the detrimental role of HLA-DQ DSA. We continue to explore why HLA-DQ, much more than any other HLA molecule, has such a significant role in AMR;
(3) Understanding how to better utilize commercial reagents to study HLA antibodies: we have shown that many of the very highly sensitized patients have inhibitory factors in their serum that may lead to a “prozone” effect which leads to – underappreciation of antibody strength using the Single Antigen Bead (SAB) Luminex assay (specifically once targets have been saturated) – in many cases, demonstrating that the patients may have more antibody than can be detected by the SAB assay. Furthermore, we have highlighted the role of the “shared epitope” phenomenon as an impediment to accurately analyze the SAB assay.
What made you decide to work in transplantation?:
It was either this or dentistry…. I finished Dental Medicine school prior to obtaining my PhD (hence my DMD degree). As part of immunology curriculum classes, I came across the fascinating field of Immunogenetics and the polymorphism of the HLA system raised my curiosity. The connection to transplantation was quite immediate and I fell in love with this field.
What do you find to be the most valuable aspect of your work?:
The word Doctor originated from the Latin verb “Doc’ere”, or – to teach. This is the most valuable aspect of my work – being an educator – of trainees (I run one of the few HLA laboratory director training fellowships); - of physicians, either via daily consultation for our patients or via presentations at conferences; - and - of anyone who is willing to stop and listen to me talk about HLA, and specifically about HLA-DQ.
How have you served AST?:
I believe the most prominent service is the establishment of the STAR (Sensitization in Transplantation: Assessment of Risk) workgroup that is aimed to advance understanding and applicability of HLA antibody and other laboratory assays in support of risk assessment in transplantation. The group has published its first report in 2018 and the second report should be coming soon. The STAR process is likely to become a bi-annual process, that similar to the BANFF workgroup is striving to educate clinicians and guide them through clinical decision making. As a benefit – I enjoy the opportunity to disseminate my knowledge. I feel very privileged to have a chance to make a difference.