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Immunological Mechanisms, Biomarkers and Prediction of Rejection with DNA Sequencing, at the ISHLT Annual Meeting

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Javier Carbone, MD, PhD
Complutense University
Madrid, Spain

This year's ISHLT annual meeting offered various symposiums, oral sessions, networking opportunities, science communication and other activities in which immunological mechanisms, biomarkers, and advances for the use of DNA sequencing to diagnose and detect heart and lung transplant rejection risks were developed. I will highlight some interesting topics that were presented.

Immunological mechanisms
Lori West showed that non-self ABH antigens (polysaccharide antigens) alone will not stimulate B-cell receptor without T-cell participation. This information suggests that antibody response to ABH structures is not T-cell independent. The potential role of CD19+CD27+IgM+ B-cells in tolerance induction of children with AB0 incompatible transplant was also suggested.

A pilot whole urinary metabolite study using Omics to monitor cardiac transplant rejection was presented by Brendan Keating (Plenary Session 05 April). Previous studies suggested that acute cellular rejection detection using urinary biomarkers including CD3?, perforin, granzyme B, proteinase inhibitor 9, CD103, IP-10 and CXCR3 mRNA is possible in kidney recipients.

Infection is a leading cause of death and morbidity in patients using VAD and ECMO. Low albumin levels have been presented as a risk factor of poor outcome in patients with VAD and ECMO. The potential role of decreased levels of other proteins warrants investigation.

J. Youn evaluated the impact of T-cell CMV-specific responses in heart recipients. Low CMV pp65 specific IFN-gamma spot number nadir levels had an impact on fatal outcomes of CMV infection.

C. Hernandez presented data demonstrating that higher donor CMV IgG optical density was associated with CMV infection in CMV seropositive lung recipients.

Other topics in this area were for example: DAMPS, PAMPS and innate immunity in CLAD (Scott Palmer); the relationship between KLRG1 gene expression by T-bet and its correlation with specific CD8 T-cell responses (John McDyer); the role of pre-transplant memory class-switched B-cells to predict severe infection after heart transplantation (Leticia Calahorra); and allergic predisposition in thymectomized children with reduced naive regulatory T-cells and B-10 cells (T.B. Kim).

Prediction with DNA sequencing
In a plenary session (05 Apr), Sean Agbor Enoh suggested that donor derived, cell free DNA reliably quantitates graft failure and death risk in lung transplant recipients.

In a Lunch Symposium, Philip Halloran, Luciano Potena and Andreas Zuckermann moderated by Jon Kobashigawa discussed about the potential role of the Molecular Microscope (Tissue-based measurements of specific pathogenesis-based transcripts reflecting NK, T-cell and endothelial activation among others) for a more precise diagnosis of acute cellular rejection and antibody-mediated rejection in heart and lung recipients. Illustrative cases of agreement between Molecular Microscope results and local pathology were presented.

There was also an exciting session about Precision Medicine. Hannah Valentine presented data about cell free DNA in transplantation applications and future directions of potential for differentiation between acute cellular rejection and antibody mediated rejection. In the same session, a conference about microbial cell-free DNA was presented by Iwijn De Vlaminck, who disclosed information regarding virome temporal dynamics of anelovirus load in rejection versus non-rejection. Microbial cell-free DNA can also identify bacterial growth dynamics and profiles of resistance. There was a very interesting talk given by Howard Eisen, on micro-RNA as biomarkers in solid organ transplantation: distinct patterns that are associated with tumor suppression, acute cellular rejection, lung allograft disease and increased expression of micro RNA in cardiac allograft vasculopathy, among other information. Transcriptomic analysis of heart allograft was analyzed by Duong Van Huyen. Bruce McManies provided interesting information about emerging roles of next generation sequencing analysis, and finally, Christoff Fellman covered genome editing using CRISPR-cas9 tools.

This meeting also aimed to promote networking and exchange of ideas in the immunology area. ■

Disclosure Statement: The author has no conflicts of interest to disclose.

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