Article

Antibody-reactive epitope determination with HLAMatchmaker and its clinical applications

Division of Transplantation Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Tissue Antigens (Impact Factor: 2.35). 03/2011; 77(6):525-34. DOI: 10.1111/j.1399-0039.2011.01646.x
Source: PubMed

ABSTRACT Antibodies against allogeneic human leukocyte antigen (HLA) molecules are important impediments to the success of different clinical procedures including transplantation and platelet transfusion. In these settings, characterization of the repertoire of immunogenic epitopes is important for permissible mismatch determination and the identification of acceptable mismatches for sensitized patients. HLAMatchmaker is a computer algorithm that considers small configurations of polymorphic residues referred to as eplets as essential components of HLA epitopes. This review critically elaborates the concepts underlying the HLAMatchmaker and describes the usefulness of HLAMatchmaker in the clinical setting. Recent developments have increased our understanding of structural basis of HLA antigenicity (i.e. reactivity with specific antibody) and immunogenicity (i.e. its ability to induce an antibody response).

0 Followers
 · 
143 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The contribution of memory B cells in alloreactive humoral responses remains poorly understood. Here we tested the presence of circulating alloreactive memory B cells in 69 patients with end-stage renal disease under renal replacement therapy, using an in vitro memory B cell-stimulation assay combined with identification of IgG human leukocyte antigen (HLA) antibodies in culture supernatant. HLA antibody-producing memory B cells were evidenced only in patients carrying serum HLA antibodies following multiple classical HLA-immunizing events. In patients with a previous renal allograft, alloreactive memory B cells could be detected ranging from 6 to 32 years (mean 13.2 years) after transplantation. HLA antibodies produced by memory B cells were also detected in the corresponding sera and showed a restricted reactivity, targeting only a few epitopes shared by several HLA antigens. In contrast, serum HLA antibodies, not associated with the detection of specific memory B cells, showed a broader pattern of specificities. Thus, expansion and survival of alloreactive memory B cells is alloantigen driven, and their frequency is related to the 'strength' of HLA immunization.Kidney International advance online publication, 7 January 2015; doi:10.1038/ki.2014.390.
    Kidney International 01/2015; DOI:10.1038/ki.2014.390 · 8.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review describes a database for the collection, archiving, sorting, searching and display of gene and allele frequencies for immunogenetic genes.
    Transfusion Medicine and Hemotherapy 10/2014; 41(5):352-5. DOI:10.1159/000368056 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The ability to efficiently and accurately diagnose the cause(s) of platelet (PLT) refractoriness is paramount in providing effective PLT products for transfusion. Recent advances in methods for detecting and identifying alloantibodies against human leukocyte antigens (HLAs) and human PLT antigens, combined with accurate molecular techniques for HLA typing, have provided a framework for the development of clinical algorithms to support such patients. Alloantibodies may be detected and/or identified by several methods, including complement-dependent cytotoxicity, enzyme-linked immunosorbent assays (ELISA), and microbead-based assays using Luminex or flow cytometry. The primary difference in these assays is the sensitivity of detection and the range of antibody specificities that may be reliably identified. Direct PLT cross-matching to identify compatible PLTs can be accomplished by several methods, including solid-phase red cell adherence, modified antigen capture ELISA, and flow cytometry. A survey of blood centers and laboratories providing transfusion support has identified the heterogeneity of testing options available, areas of concern and need for improvement, and common obstacles in providing appropriate and timely support to immune-refractory PLT patients. Depending on the testing methods and the pool of HLA-typed PLT donors available, there are numerous options for developing suitable algorithms to provide effective support to immune-refractory PLT patients.
    Transfusion 11/2014; 55(2). DOI:10.1111/trf.12921 · 3.57 Impact Factor

Preview

Download
4 Downloads
Available from