Novel strategies for immunological monitoring of kidney transplant recipients: from microRNA to alloantibodies.
Authors: Heidt S, Eikmans M, Roelen DL, Claas FH
Abstract
Predicting and diagnosing acute kidney allograft rejection by non-invasive biomarkers is a major goal in clinical transplantation research. Such biomarkers can be reduced to the various stages of the alloimmune response, from transcriptional regulation to immunological effector mechanisms. Here, we describe novel insights into exciting areas of transplantation-related biomarker research that may be translated to non-invasive monitoring strategies. First, we will elaborate on microRNAs, which represent stable, small non-coding ribonucleic acid molecu...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Cells versus antibodies in allograft destruction - A historical perspective.
Authors: Brent L
PMID: 25095517 [PubMed - indexed for MEDLINE] (Source: Clinical Transplants)
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Understanding recurrent glomerulonephritis in renal transplants: 50 years of progress.
Authors: Glassock RJ
Abstract
Glomerulonephritis that resulted in end-stage renal disease in a transplant recipient can recur in the iso- or allo-grafted kidney. Fifty years ago seminal observations identified the extent and nature of such recurrences of original diseases in iso-grafts and evidence has accumulated over the subsequent decades that recurrent glomerulonephritis is not uncommon in allografts, although its frequency and clinical significance varies widely according to the type and aggressiveness of the specific form of glomerular disease. Much progress has been made in characterizing the risk o...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Plasma cell biology: principles for therapeutic design.
Authors: Woodle ES, Alloway RR, Ejaz NS
Abstract
Plasma cells represent the terminally differentiated cell population of the B-lymphocyte lineage. Plasma cells possess a unique biology, primarily as a result of their role as antibody factories. The unique features associated with the massive antibody production capacity confer upon the plasma cell a vulnerability to attack by specific targeted therapies. Over the past nine years, we have worked to develop therapies that exploit the unique features of plasma cells - therapies we have termed plasma cell targeted therapies. To date, these therapies have been ...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Evolving concepts in desensitization.
Authors: Jordan SC, Vo AA
PMID: 25095520 [PubMed - indexed for MEDLINE] (Source: Clinical Transplants)
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Anti-HLA-E monoclonal antibodies reacting with HLA-la and lb alleles like IVIg as potential IVIg-immunomimetics: an evolving therapeutic concept.
Authors: Ravindranath MH, Zhu D, Pham T, Jucaud V, Hopfield J, Kawakita S, Terasaki PI
Abstract
Healthy individuals have natural antibodies (Abs) reacting to allo-human leukocyte antigen (HLA)-la. This could be due to the presence of anti-HLA-E immunoglobulin G (IgG), which was revealed to recognize the peptides shared between HLA-E and HLA-la after peptide inhibition assay. Sera or plasma of multiple donors are pooled to prepare intravenous immune globulin (IVIg). The HLA-la-reactivity of IVIg is abolished when the anti-HLA-E Abs are depleted from the IVIg, suggesting that IVIg contains anti-HLA-E Abs wit...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
ABO-incompatible kidney transplantation: long-term outcomes.
Authors: Tanabe K, Ishida H, Inui M, Okumi M, Shirakawa H, Shimizu T, Omoto K, Kondo T
Abstract
In the past 20 years, over 2,000 cases of ABO-incompatible living kidney transplantation (ABO-ILKT) have been performed in Japan, expanding the donor pool and overcoming the serious shortage of organ donors. Overall long-term outcomes (>20 years) have been excellent and almost identical to the outcomes of ABO-compatible living kidney transplantation (ABO-CLKT). In the last decade, ABO-ILKT has become accepted as a therapeutic alternative for end-stage renal failure. Recently, approximately 30% of all living d...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Incidence and hazards of alloantibodies in renal transplantation.
Authors: Everly MJ
Abstract
In the last 10 years, many reports on the impact of antibodies against human leukocyte antigens (HLA) have been published. Now, in 2014, the overwhelming consensus is that antibodies cause allograft failure. Based on reports from East Carolina University, we now know that approximately 10% of patients will develop de novo donor specific anti-HLA antibodies (DSA) by 1-year post-transplant. Within 5 years, 20% of all transplanted patients will have de novo DSA. In those who develop de novo DSA, allograft failure rates are significantly higher than that of patients who do not devel...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Novel biomarker combination predicts long-term allograft outcome.
In conclusion, serum BMC is an independent predictor of graft failure. BMC was more significantly associated with graft failure than DSA. In combination with DSA, BMC better predicted graft outcome than DSA or BMC alone.
PMID: 25095524 [PubMed - indexed for MEDLINE] (Source: Clinical Transplants)
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Role of alloimmunity and autoimmunity in allograft rejection.
Authors: Banan B, Xu Z, Gunasekaran M, Mohanakumar T
Abstract
Pathophysiology of chronic rejection strongly supports that inflammation and subsequent tissue remodeling during the post-transplant period cause exposure of cryptic self-antigens (SAgs) or their determinants within the graft, which, along with a subsequent cytokine response, leads to loss of peripheral tolerance. These events lead to the activation of cell-mediated immunity towards development of de novo immune responses to SAgs. There is also evidence for a role for interplay between allo- and autoimmunity in the development of chronic rejecti...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Antibodies against "DANGER" in the dynamic of post-transplant circulation.
Authors: Taniguchi M
Abstract
Evidence that has accumulated about the impact of non-human leukocyte antigen (HLA) antibodies against tissue-restricted antigens supports the concept that humoral targets can be constantly altered by transplant-associated stresses such as ischemia-reperfusion (IR) injury, organ preservation, immunosuppressive drugs, and pre-existing diseases. This accounts for the growing interest in "danger" signals--in the form of damage-induced molecules--expanding our understanding of the humoral cause of allograft rejection and failure from thinking it is caused only by genetically deter...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Pre-transplant angiotensin II type 1 receptor antibodies: A risk factor for decreased kidney graft function in the early post-transplant period?
This study aimed to evaluate graft function and biopsy proven acute rejection (BPAR) during the first year post-transplant in adult renal transplant recipients (RTR), between 03/2009 and 08/2012. Pre-transplant sera were screened for AT1Rab (via enzyme linked immunosorbent assay) and donor specific anti-human leukocyte antigen antibodies (HLA-DSA, via Luminex). Three groups were analyzed: AT1Rab only (n=13); HLA-DSA only (n=8); and no AT1Rab or HLA-DSA (n=90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference wa...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Pre-nephrectomy angiotensin II type 1 receptor antibodies in living kidney donors: A concern?
In this study, sera obtained the day before nephrectomy and kept frozen at -70 degrees C from 113 strictly normotensive and non-obese LKD were tested for AT1Rab by OneLambda detection assay. AT1Rab titers >or=17 international units were considered positive. Pre-donation renal function [estimated glomerular filtration rate (eGFR)] and blood pressure at 1 and 12 months post-donation were recorded in every patient. Ten of 113 (8.8%) LKD yielded a positive AT1Rab result. History of sensitization events was similar in both groups. There was no difference in renal function between LKD with positive and negative AT1Rab results...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Can we use dilution-titration studies to identify clinically relevant HLA antibody specificities?
Authors: Kerman R, Saltarrelli J, McKissick E, Eaton J, Woolley N, Hoover A, Acorda N, Erice P, Hollingsworth C, Chappelle J, O'Mahony C, Van Buren C
Abstract
These data suggest the presence of virtual crossmatch positive, low titer donor specific anti-human leukocyte antigen antibody (DSA) positive sera does not guarantee that real-time crossmatches will be positive. DSA that are present at an undiluted concentration but absent at a 1:8 or 1:16 dilution may not have to be considered unacceptable. This would allow potential recipients wider access to donor organs by reducing the number of listed unacceptab...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Unravelling the connections between donor specific antibodies and renal allograft pathology.
Authors: Chapman JR, Wavamunno M, O'Connell PJ, Nankivell BJ
Abstract
The imperfections of early technologies for assessment of human leukocyte antigen (HLA) antibody specificity have been resolved by solid phase micro bead assays, but this has revealed new uncertainties. The relationship between presence of antibody specific for a donor HLA molecule to graft damage and outcomes has had to be re-evaluated. Studies of protocol biopsies have identified a correlation between donor specific antibody and electron microscopy (EM) changes at three months, which do not predict chronic antibody mediated rejection, ...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
