Identification of risk epitope mismatches associated with de novo donor-specific HLA antibody development in cardiothoracic transplantation

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
J A McCaughanK J Tinckam

Abstract

The development of de novo donor-specific HLA antibodies (dnDSA) after transplantation is associated with graft failure, mortality, and cost. There is no effective therapeutic intervention to prevent dnDSA or ameliorate associated injury. The aims of this study were to identify specific HLA factors associated with dnDSA development and to propose primary prevention strategies that could reduce the incidence of dnDSA without prohibitively limiting access to transplant. The investigation cohort included heart transplant recipients from 2008 to 2015 (n = 265). HLA typing was performed and HLA antibody testing was undertaken before and after transplantation. HLAMatchmaker analysis was performed for persistent dnDSA to identify potentially more immunogenic eplet differences. Validation was performed in recipients of lung transplants from 2008 to 2013 (n = 433). The majority of recipients with dnDSA had antibodies to identical eplet positions on DQ2 and DQ7. A high-risk epitope mismatch (found in DQA1*05 +  DQB1*02/DQB1*03:01(7)) was associated with a 4.2- and 4.9-fold increased risk of dnDSA in heart and lung recipients respectively. HLA electrostatic potential modeling provided a plausible explanation for this observed immunogenici...Continue Reading

References

Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Jan 12, 2011·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·J D SmithM L Rose
Oct 12, 2012·Journal of Biomedical Science·Francesca Megiorni, Antonio Pizzuti
May 21, 2013·Transplant Immunology·I C BostockM Vilatobá
Sep 27, 2013·The New England Journal of Medicine·Alexandre LoupyXavier Jouven
Oct 30, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·C WiebeP W Nickerson
Mar 13, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·B J FosterJ A Hanley
Jul 9, 2014·Transplantation·Anat R TamburJoseph R Leventhal
Jul 24, 2014·The New England Journal of Medicine·Loren GragertMartin Maiers
Aug 19, 2014·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Shahideh SafaviJohn D Smith
Dec 3, 2014·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Matthew R MorrellAdriana Zeevi
Dec 19, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R Sapir-PichhadzeS J Kim
Jan 24, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·K J TinckamL G Singer
Mar 26, 2015·Journal of the American Society of Nephrology : JASN·Ana Konvalinka, Kathryn Tinckam
Oct 1, 2015·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Andrew TranBibhuti B Das
Mar 12, 2016·American Journal of Respiratory and Critical Care Medicine·Jussi M TikkanenKathryn Tinckam
Mar 24, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·D C WaltonG P Westall
Dec 15, 2016·Frontiers in Immunology·Rene J Duquesnoy
Mar 4, 2017·Journal of the American Society of Nephrology : JASN·Olivier AubertPhilip F Halloran

❮ Previous
Next ❯

Citations

Aug 1, 2018·Transplant International : Official Journal of the European Society for Organ Transplantation·Jennifer A McCaughan, Kathryn J Tinckam
Feb 26, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Anita S ChongLeonardo V Riella
Jun 6, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Anat R TamburDavid F Pinelli
Oct 11, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Mary Carmelle PhilogeneCozumel S Pruette
Apr 1, 2020·HLA : Immune Response Genetics·Cynthia S M KramerSebastiaan Heidt
Oct 4, 2020·BMC Pulmonary Medicine·Sakiko KumataYoshinori Okada
Oct 18, 2020·HLA : Immune Response Genetics·Lara SchawalderStefan Schaub
Jan 12, 2021·International Journal of Immunogenetics·William LemieuxRuth Sapir-Pichhadze
Dec 7, 2018·Current Opinion in Organ Transplantation·Jeffrey J KiernanKathryn J Tinckam
Mar 18, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Scott M KrummeyHarold C Sullivan
Jun 9, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Olga CharnayaJacqueline Garonzik-Wang
Jun 1, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Meghan AversaKathryn Tinckam
Jun 26, 2021·KI Reports·Matthew P Sypek, Peter Hughes
May 29, 2019·Current Opinion in Organ Transplantation·Nicholas G LarkinsWai H Lim

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.