The Importance of Non-HLA Antibodies After Heart Transplant

AbstractPurpose of ReviewAntibodies to human leukocyte antigens (HLA) are associated with adverse patient and allograft outcomes after heart transplantation. Non-HLA antibodies have increasingly been recognized as important mediators of rejection, cardiac allograft vasculopathy (CAV), and allograft injury. In particular, these antibodies have been implicated in a subset of heart transplant recipients who have clinical and/or pathologic evidence of antibody-mediated rejection in the absence of detectable antibodies against HLA.Recent FindingsNon-HLA antigens have been identified to have important roles in both the innate and adaptive immune response in transplantation. These antigens are predominantly expressed on vascular endothelium of the donor heart and include major histocompatibility class I related chain A (MICA), G protein coupled receptor angiotensin II type 1 receptor (AT1R), cytoskeletal elements such as myosin and vimentin. A growing number of studies have demonstrated antibodies to these antigens in rejection and development of CAV. At present, non-HLA antibodies are not routinely monitored post-transplant, and laboratory evaluation remains non-standardized. Further investigation is required to improve the detection of non-HLA antibodies, define pathophysiological mechanisms involved in allograft injury, and better understand their impact on clinical outcomes.SummaryNon-HLA antibodies have been identified as important mediators of rejection, allograft dysfunction,...
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research

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AbstractBackground and objective The main objective was to evaluate the impact of Hepatitis C Virus treatment with direct-acting antiviral agents on tacrolimus blood levels in recipients of kidney and heart allografts.Method We analysed Hepatitis C Virus infected adult patients who received tacrolimus as immunosuppressive maintenance therapy and received direct-acting antiviral agents treatment in a tertiary hospital with solid transplant multidisciplinary program in Madrid, Spain. Liver and renal function, tacrolimus dose and blood levels were analysed before and 12  weeks after the end of treatment.Results We identi...
Source: International Journal of Clinical Pharmacy - Category: Drugs & Pharmacology Source Type: research
Conclusions: There is an association between PVB19 and HHV-6 infection and DCM in children. The study suggests the persistence of PVB19 and HHV-6 in the host can lead to subsequent viral reactivation in the transplanted heart, even in those recipients who do not have active myocarditis. PVB19 in the cardiac allograft tended toward higher adverse post-HT events.
Source: Annals of Pediatric Cardiology - Category: Cardiology Authors: Source Type: research
Abstract We have previously demonstrated the unique properties of a new triazolopyrimidine derivative, NK026680, which exerts immunosuppressive effects in rat heart transplant model and confers tolerogeneic properties on ex vivo-conditioned dendritic cells in mice. We herein demonstrate that NK026680 promotes the expansion of regulatory T cells (Tregs) with potent immunoregulatory effects when used in combination with donor-specific transfusion (DST). BALB/c (H-2d) heart graft were transplanted into C57BL/6 (H-2b) mice following intravenous injection of donor splenocytes (DST) and oral administration of NK026680. ...
Source: Transplant Immunology - Category: Transplant Surgery Authors: Tags: Transpl Immunol Source Type: research
AbstractWe have previously demonstrated that Mettl3-silencing dendritic cells (DCs) exhibited immature properties and prolonged allograft survival in a murine heart transplantation model. Exosomes derived from donor DCs (Dex) are involved in the immune rejection of organ transplantation, and blocking Dex transfer may suppress immune rejection. Herein, this study aimed to investigate whether Mettl3 knockdown inhibits the secretion and activity of donor Dex, thereby inhibiting donor Dex –mediated immune rejection. The imDex, mDex, shCtrl-mDex, and shMettl3-mDex were obtained from the culture supernatant of DCs (immatur...
Source: Immunogenetics - Category: Genetics & Stem Cells Source Type: research
Publication date: October 2020Source: Canadian Journal of Cardiology, Volume 36, Issue 10, SupplementAuthor(s): N. Aleksova, D. Brahmbhatt, O. Kiamanesh, J. Petropoulos, Y. Chang, G. Guyatt, H. Ross, S. Chih
Source: Canadian Journal of Cardiology - Category: Cardiology Source Type: research
Cardiac allograft vasculopathy (CAV) is known as the primary cause of death in the first year after orthotopic heart transplant (OHT). Coronary artery spasm (CAS) in OHT is a rare and under-recognized phenomenon in patients undergoing surveillance. The mechanism of coronary vasospasm in OHT remain largely unknown. The presentation can vary from an incidental finding to severe episodes of symptomatic ventricular arrhythmias, high-degree atrioventricular block, syncope, cardiac arrest, or even myocardial infarction in cases of prolonged ischemia.
Source: Journal of Cardiac Failure - Category: Cardiology Authors: Tags: 459 Source Type: research
HLA matching is not current practice in heart transplant (HT) donor allocation due to scarcity of donor organs and ischemic time. However HLA mismatch might adversely affect transplant outcomes. Even if HLA matching is not possible the degree of HLA mismatch might help inform clinicians on a patients risk for long term transplant complications.
Source: Journal of Cardiac Failure - Category: Cardiology Authors: Tags: 456 Source Type: research
Endomyocardial biopsy (EMB) is routinely performed for surveillance of allograft rejection following heart transplantation (HTx). HTx recipients who are on anticoagulation are at higher risk for complications such as bleeding at access site, pericardial effusion, and cardiac tamponade. The safety of apixaban for periprocedural anticoagulation in heart transplant recipients undergoing EMB is not well characterized.
Source: Journal of Cardiac Failure - Category: Cardiology Authors: Tags: 114 Source Type: research
HMG CoA Reductase Inhibitors, commonly referred to as statins, are widely used in heart transplant patients as dyslipidemia is common after cardiac transplantation and increases the risk of cardiovascular adverse events including cardiac allograft vasculopathy (CAV). However, not all patients can tolerate statins or see an adequate lowering of the low density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors have been shown to be effective at lowering LDL with great tolerance and excellent safety profiles in the general population.
Source: Journal of Cardiac Failure - Category: Cardiology Authors: Tags: 301 Source Type: research
Conclusions. Normalized peak VO2 ≤60% and VE/VCO2 ≥34 at 1 year after HTx are associated with the development of CAV.
Source: Transplantation - Category: Transplant Surgery Tags: Original Clinical Science—General Source Type: research
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