Post-transplant development of C1q-positive HLA antibodies and kidney graft survival.
This study demonstrated that C1q-fixing capability of de novo DSA is a clinically relevant marker of worse outcome and inferior graft survival in kidney transplantation. In fact, our findings evidenced a very low graft survival only in the patients who developed DSA able to fix C1q during post-transplant course, while patients producing C1q-negative DSA had good graft survival, which was comparable to that found in our previous study for DSA-negative patients. Moreover, anti-HLA class II antibodies had a higher incidence than anti-HLA class I, and the ability to fix C1q was significantly more frequent among anti-DQ DSA tha...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
The differential pathogenicity of HLA antibodies: what a large cross-sectional study can tell us.
In conclusion, the predictive value of detecting Clq-binding capability provides further perspectives for patient risk stratification to improve long-term renal allograft outcome.
PMID: 25095532 [PubMed - indexed for MEDLINE] (Source: Clinical Transplants)
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Clinical relevance of pre- and post-transplant HLA antibodies, donor-specific, and nondonor-specific HLA antibodies detected by ELISA in renal transplantation.
In conclusion, pre-transplant NDSA and post-transplant DSA were associated with poor long-term graft survival. For patients who had persistent pre- and post-transplant HLA antibodies, the worst long-term survival could be found. We believe HLA antibody analysis by ELISA is still very useful for transplantation.
PMID: 25095533 [PubMed - indexed for MEDLINE] (Source: Clinical Transplants)
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Impact of solid phase antibody testing on organ allocation in the United States.
Authors: Reinsmoen NL
Abstract
The implementation of the solid phase antibody assays has allowed for the detection and characterization of human leukocyte antigen (HLA) specific antibodies with greater sensitivity and specificity. This information can then be used along with the donor's HLA typing to predict crossmatch results (a virtual crossmatch). Using these data and the level of immunological risk assessed to the antibodies detected, the determination of unacceptable antigens can be made. The calculated panel reactive antibody (CPRA) provides for a means to determine the frequency of these unacceptabl...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
The big picture: A case report of antibody mediated rejection and treatment after lung transplantation illustrating the need to correlate laboratory findings with clinical status.
We report the case of a patient who developed respiratory failure in the presence of de novo donor-specific antibody (DSA) two years after lung transplantation, following recurrent acute cellular rejection. The patient underwent salvage therapy with plasma exchange, intravenous immunoglobulins, and proteasome inhibitor carfilzomib (CFZ). DSA was detected prior to admission for antibody-mediated rejection by single antigen bead Luminex (SAB) testing and indicated the presence of a DQ3 pattern (DQ7, DQ8, and DQ9). The patient initially responded to CFZ-based treatment with a decline in DQ3-DSA strengths, but DQ7-DSA persiste...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Donor specific antibodies before and after kidney transplant: the University of Colorado Experience.
Authors: Cooper JE, Gralla J, Adebiyi O, Wiseman AC, Chan L
Abstract
We summarize in this manuscript our donor specific antibody (DSA) screening experience in the past six years as it applies to pre-existing DSA, de novo DSA, and post-transplant DSA treatment. Of 547 patients receiving a kidney or kidney/pancreas with negative pre-transplant flow cytometry crossmatch (FCXM), 196 had DSA (mean fluorescence intensity, MFI >or= 500) detected prior to transplant by single antigen bead analysis. Acute rejection rates at one year were similar in DSA+ versus DSA- (15% versus 12%, respectively, p=0.22), althoug...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Immunoglobulin G subclass analysis of HLA donor specific antibodies in heart and renal transplant recipients.
Authors: Cicciarelli JC, Kasahara N, Lemp NA, Adamson R, Dembitsky W, Browne B, Steinberg S
Abstract
Immunoglobulin G (IgG) subclasses IgG1 (G1) and lgG3 (G3) can induce complement dependent cytotoxicity (CDC) and bind to Fc receptors (FcR), which induces phagocytosis and antibody dependent cellular cytotoxicity. In contrast, IgG2 has low CDC activity, lgG4 (G4) has no CDC activity, and neither binds high affinity FcR. Seven transplant recipients were analyzed for G1- G4 human leukocyte antigen (HLA) donor-specific antibodies (DSAs); six had active rejection and one had stable function. Patients with rejec...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
A critical analysis of quantitating flow cytometry: the role of the crossmatch in 2014.
Authors: Rosenberg JC, Eisenbrey AB, Jackowski M, Levis D, Peiter C, Putnam K, Tanner K, Ho CS
Abstract
The mean fluorescent intensity obtained using single antigen beads does not represent the titer of the serum sample very well because the degree of saturation of the antigen on the bead varies by individual bead and the human leukocyte antigen antibody-binding site on the bead may not duplicate the activity of the serum's antibodies in vivo. The flow crossmatch appears to come closer to correlating with the titer. As we have shown, the titer will roughly correlate with the flow crossmatch. This is conson...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
HLA-specific antibody distribution in renal transplant waiting list patients: utility of antigen frequency data in the definition of HLA-reactive epitopes.
This study describes how the use of antigen frequency data can be used to support the identification of HLA-reactive epitopes. It also highlights how sharing of epitopes can explain SAB reactivity against HLA antigens found at extremely low frequency in the population.
PMID: 25095539 [PubMed - indexed for MEDLINE] (Source: Clinical Transplants)
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
HLA matching at the epitope level: the way to go.
Authors: Duquesnoy RJ
Abstract
Human leukocyte antigen (HLA) mismatches are important risk factors for antibody-mediated rejection and transplant failure. With the realization that HLAantibodies recognize epitopes rather than antigens, it has become apparent that donor-recipient compatibility should be assessed at the epitope level. Recent developments have increased our understanding of the structural basis of HLA antigenicity (i.e. the reactivity with specific antibody) and immunogenicity (i.e. the ability to induce an antibody response). HLAMatchmaker is a computer algorithm that considers each HLA anti...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Evolution of studies of HLA class I antigen processing machinery (APM) components in malignant cells.
Authors: Sabbatino F, Schwab JH, Ferrone S, Ferrone CR
Abstract
Following a description of the way studies of human leukocyte antigen (HLA) class I antigen expression by tumor cells have evolved through the years, the literature related to the frequency of defects in HLA class I antigen processing machinery (APM) component expression in various types of malignancies is reviewed. In addition, the clinical significance of defects in HLA class I APM components as well as the underlying molecular mechanisms are described. Lastly, potential strategies to overcome the defects in HLAclass I APM component expressi...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
The non-classical antigens of HLA-G and HLA-E as diagnostic and prognostic biomarkers and as therapeutic targets in transplantation and tumors.
Authors: Seliger B
Abstract
The non-classical human leukocyte antigen (HLA) class I antigen HLA-G represents a tolerogenic molecule and is involved in the inhibition of natural killer cell and cytotoxic T lymphocyte-mediated cytotoxicity. Under physiological conditions, HLA-G expression is mainly restricted to immune-privileged tissues, whereas it is overexpressed in tumors and transplants as well as in virus-infected cells. Due to its immunosuppressive features, HLA-G is important for pregnancy or organ transplantation and autoimmune diseases as well as cancer immune escape. This review focusses on the ex...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
The UNOS Renal Transplant Registry: Review of the Last Decade.
Authors: Andre M, Huang E, Everly M, Bunnapradist S
Abstract
Kidney transplantation has become a preferred treatment for end-stage renal disease (ESRD) as transplant recipients enjoy freedom from dialysis and improvement in both quality and quantity of life. More patients are being placed on the transplant waiting list, although the waiting list patients still only represent a very small fraction of ESRD patients. The characteristics of both waitlisted and transplanted patients have changed considerably in the last decade, as the ESRD population has aged and waiting list times have increased. Over the last...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
Trends of Immunosuppression and Outcomes Following Liver Transplantation: An Analysis of the United Network for Organ Sharing Registry.
Authors: Cheng EY, Everly MJ
Abstract
Advances in immunosuppression (IS) agents and strategies have resulted in reduced rejection rates and improved survival outcomes after liver transplantation. The use of induction and maintenance IS agents is both associated with reductions in acute rejection (AR) risk within the first 6 to 12 months posttransplant and with superior failure-free survival. With the lowered incidence of allograft losses attributable to rejection, the long-term sequelae of IS have become the major therapeutic challenge. The long-term use of calcineurin inhibitors and corticosteroids in mai...
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
An Update on Cardiac Transplantation in the United States.
Authors: Everly MJ
Abstract
Heart transplantation in the United States remains an important option for those with heart failure. Survival rates over the last 25 years have improved with the advent of newer immunosuppressive agents, innovation, and a better understanding of managing risk. However, many patients continue to experience allograft failure after transplantation. Innovations in modalities to reduce acute and chronic rejection are needed to improve the long-term success of heart transplantation.
PMID: 26281124 [PubMed - indexed for MEDLINE] (Source: Clinical Transplants)
Source: Clinical Transplants - November 20, 2015 Category: Transplant Surgery Tags: Clin Transpl Source Type: research
