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Conformational Variants of the Individual HLA-I antigens on Luminex Single Antigen Beads used in Monitoring HLA Antibodies: Problems and Solutions.

Published on Apr 1, 2017in Transplantation4.593
· DOI :10.1097/TP.0000000000001420
Vadim Jucaud6
Estimated H-index: 6
,
Mepur H. Ravindranath3
Estimated H-index: 3
,
Paul I. Terasaki91
Estimated H-index: 91
Abstract
BackgroundSingle antigen beads (SAB) are used for monitoring HLA antibodies in pretransplant and posttransplant patients despite the discrepancy between virtual and actual crossmatch results and transplant outcomes. This discrepancy can be attributed to the presence of conformational variants of HLA
  • References (44)
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References44
Newest
#1Baoshan GaoH-Index: 7
#2Chunshu RongH-Index: 2
Last. Emmanuel ZornH-Index: 21
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Assessing the serum reactivity to HLA is essential for the evaluation of transplant candidates and the follow-up of allograft recipients. In this study, we look for evidence at the clonal level that polyreactive antibodies cross-reactive to apoptotic cells and multiple autoantigens can also react to HLA and contribute to the overall serum reactivity.We immortalized B cell clones from the blood of 2 kidney transplant recipients and characterized their reactivity to self-antigens, apoptotic cells ...
14 CitationsSource
#1Jonathan Visentin (University of Bordeaux)H-Index: 10
Last. Jean-Luc Taupin (University of Bordeaux)H-Index: 29
view all 8 authors...
In addition to antibodies targeting native class I human leukocyte antigens (HLA), the single antigen flow beads assay (SAFB) detects antibodies recognizing denatured forms (anti-dHLA). Acid treated SAFB and the modified SAFB reagent named iBeads are expected to distinguish anti-native (anti-nHLA) from anti-dHLA. Sera from 280 class I HLA-sensitized SAFB-positive kidney transplant candidates were retested with acid-treated SAFB and iBeads. Concordance between SAFB and iBeads, taking into account...
10 CitationsSource
#1Jonathan Visentin (University of Bordeaux)H-Index: 10
#2Mélanie MarrocH-Index: 1
Last. Jean-Luc Taupin (University of Bordeaux)H-Index: 29
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Class I single-antigen flow beads (SAFB) carry native and denatured human leukocyte antigen (HLA) molecules. Using a cohort of 179 class I HLA-sensitized kidney recipients, we described incidence and clinical relevance of preformed denatured HLA donor-specific antibodies (DSA) using two different assays: an acid-treated SAFB assay (anti-dHLA DSA) and the iBeads assays (SAFB+/iBeads- DSA). Eighty-five class I DSA were found in 67 patients (median mean fluorescence intensity [MFI] of 1729 [range 5...
20 CitationsSource
#1Juan José Mata Molanes (University of Navarra)H-Index: 1
#2Leire Burgos Rodríguez (University of Navarra)H-Index: 1
Last. A. Sánchez-Ibarrola (University of Navarra)H-Index: 10
view all 10 authors...
1 CitationsSource
Summary Activated CD4+ T cells undergo blastogenesis and proliferation and they express several surface receptors, including β2-microglobulin-free human leucocyte antigen (HLA) heavy chains (open conformers). Intravenous immunoglobulin (IVIg) suppresses activated T cells, but the mechanism is unclear. IVIg reacts with HLA-Ia/Ib antigens but its reactivity is lost when the anti-HLA-E Ab is adsorbed out. Anti-HLA-E antibodies may bind to the peptides shared by HLA-E and the HLA-I alleles. These sh...
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#1Jonathan VisentinH-Index: 10
Last. Jean-Luc TaupinH-Index: 29
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#1Howard M. Gebel (Emory University)H-Index: 33
#2Robert A. Bray (Emory University)H-Index: 38
Alloantibodies directed against HLA antigens, are a barrier to long-term solid organ allograft survival. The clinical impact of preformed, donor-directed HLA alloantibodies range from acceptable risk to unequivocal contraindication for organ transplantation. HLA antibodies are key factors that limit patient access to donor organs. Serological methods were once the only approach to identify HLA antigens and antibodies. Limitations in these technologies led to the development of solid phase approa...
73 CitationsSource
#1Elaine F. Reed (UCLA: University of California, Los Angeles)H-Index: 50
#2P. Rao (UCLA: University of California, Los Angeles)H-Index: 3
Last. David W. Gjertson (UCLA: University of California, Los Angeles)H-Index: 47
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This is a commentary on article Maillard N, Mariat C.Solid-phase bead-based assays limitations are not restricted to interlaboratory variability. Retina. 2013;13(11):3049.
35 CitationsSource
#1Eiji Kurimoto (Nagoya City University)H-Index: 18
#2Kimiko Kuroki (Hokkaido University)H-Index: 12
Last. Koichi Kato (Nagoya City University)H-Index: 50
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Abstract Despite well-organized peptide-loading mechanisms within the endoplasmic reticulum, major histocompatibility complex class I (MHC-I) molecules can be displayed on cell surfaces in peptide-free forms. Although these empty MHC-I (eMHC-I) molecules are presumably involved in physiological and pathological processes, little is known about their structures and functions due to their instability. Using bacterially expressed HLA-Cw*07:02 heavy chain and β 2 microglobulin molecules, we successf...
19 CitationsSource
Abstract Since being proposed nearly 25 years ago that MHC-I molecules free of peptide ligand possess a conformation that is distinct from that of the mature loaded form, considerable research has been conducted in order to isolate and characterise such a species. While some progress has been made in our understanding, many questions still surround the nature and loading of empty MHC-I. However, the necessary tools to address these questions may finally be at hand.
4 CitationsSource
Cited By8
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#1B. Sean CareyH-Index: 3
#2K.V. Poulton (Manchester Royal Infirmary)H-Index: 12
Last. Anthony PolesH-Index: 1
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Human leukocyte antigens (HLA) are present on the surface of all nucleated cells, with the level of expression dependent on the particular HLA locus, the cell type and cellular activation state. Human umbilical vein endothelial cells (HUVECs) are easily isolated from umbilical cords and may aid our understanding of HLA expression on the vascular endothelium in the setting of transplantation. Endothelial cells on the donor-recipient interface form the barrier between transplanted organs and the h...
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#1Stacey BrannH-Index: 1
#2Steven S. GeierH-Index: 2
Last. Yoshiya ToyodaH-Index: 36
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#1Danny YoungsH-Index: 2
#2Paul WarnerH-Index: 8
Last. Idoia GimferrerH-Index: 12
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Abstract The majority of polymorphisms of the Human Leukocyte Antigen (HLA) proteins are clustered at the peptide binding domain (PBD), defined as the area coded by exon 2 and 3 for class I and exon 2 for class II. HLA alleles with the same amino acid (AA) sequence at the PBD are considered functionally equivalent and can be grouped under the same P-group designation. Here we present a case of a kidney recipient, typed as DQA1*01:04, 01:05 and DQB1*05:01P, 05:03, who developed antibodies against...
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#2Edward J. Filippone (Thomas Jefferson University)H-Index: 8
Last. Soldano Ferrone (Harvard University)H-Index: 91
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The accurate measurement of anti-HLA alloantibodies in transplant candidates is required for determining the degree of sensitization and for the listing of unacceptable antigens for organ allocation. Both the configuration of the HLA molecules coated on the beads and the nature of detection antibodies may impede assessment of the presence and strength of anti-HLA IgG- with the Luminex single-antigen-bead assay. Sera antibodies of the end-stage renal disease patients were compared using LIFECODES...
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#2Vadim JucaudH-Index: 6
Last. Soldano Ferrone (Harvard University)H-Index: 91
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Abstract Luminex single antigen bead (SAB) assay utilizes beadsets coated with a set of cloned and purified HLA molecules, for monitoring serum anti-HLA antibodies. Particularly, the level of serum IgG against native HLA-I trimers (heavy chain (HC) and β2-microglobulin (β2 m) with a peptide), expressed in allograft tissues is correlated with graft failure. In addition to native trimeric HLA I, the beadsets may carry HC only or the dimeric variants, peptide-free HC with β2 m and β2 m–free HC with...
5 CitationsSource
#2Vadim JucaudH-Index: 6
Last. Paul I. TerasakiH-Index: 91
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Luminex multiplex immunoassays enable simultaneous monitoring of Abs against multiple Ags in autoimmune, inflammatory, and infectious diseases. The assays are used extensively to monitor anti-HLA Abs in transplant patients for donor organ selection, desensitization, and assessing the risk for graft rejection. To monitor IgG Abs, fluoresceinated IgG constant H chain–binding polyclonal F(ab′) 2 ( IgHPolyFab ) is used as the fluoresceinated secondary Ab (2nd-Ab), whereas IgG subclasses are monitore...
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The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients w...
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