Quantification of HLA class II-specific memory B cells in HLA-sensitized individuals

Karahan, Gonca E.; Vaal, Yvonne J.H. de; Roelen, Dave L.; Buchli, Rico; Claas, Frans H.J.; Heidt, Sebastiaan

doi:10.1016/j.humimm.2015.01.014

Cited by 34 publications

(44 citation statements)

References 31 publications

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“…32 More recently, Jahnmatz et al 34 comparing different stimulation procedures did also report that a polyclonal stimulation based on R848 and interleukin 2 was the most efficient expanding mBCs, allowing a very sensitive detection of antigen-specific antibody-producing B cells in the context of active immunization. Differently from a previously reported HLA B-cell ELISpot method, 35,36 our method allowed us to use peripheral blood mononuclear cells rather than sorted B cells and obtain an appropriate amount of IgG-ASCs for its subsequent HLA-specific quantification. In addition, as frequencies of HLA-sp mBCs are relatively low, antibody (Ab) levels in sera and human leukocyte antigenspecific (HLA-sp) memory B-cell (mBC) frequencies.…”

Section: Discussionmentioning

confidence: 99%

Preformed circulating HLA-specific memory B cells predict high risk of humoral rejection in kidney transplantation

Lúcia

Luque

Crespo

et al. 2015

Kidney International

104

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The accurate evaluation of donor-specific antibodies (DSAs) has allowed a precise identification of sensitized patients at risk of antibody-mediated rejection (ABMR). However, the scale of the humoral response is not always fully addressed, as it excludes the complete memory B-cell (mBC) pool such as that caused by antigen-specific mBC. Using a novel B-cell ELISpot assay approach, we assessed circulating mBC frequencies against class I and II HLA antigens in highly sensitized and nonsensitized patients in the waiting list for kidney transplantation. Also, kidney transplant patients undergoing ABMR were evaluated for the presence of donor-specific mBCs both at the time of rejection and before transplantation. For this purpose, 278 target HLA-sp antigens from 70 patients were studied and compared to circulating HLA-sp antibodies. Both class I and II HLA-sp mBC frequencies were identified in highly sensitized individuals but not in nonsensitized and healthy individuals, many years after first sensitization. Also, high donor-specific mBC responses were clearly found both during ABMR and before transplantation, regardless of circulating DSA. The higher the donor-specific mBC response, the more aggressive the allograft rejection. Thus, assessing donor-specific mBC frequencies may be relevant to better refine patient alloimmune-risk stratification, and provides new insight into the mechanisms of the adaptive humoral alloimmune response taking place in kidney transplantation.

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Section: Discussionmentioning

confidence: 99%

Preformed circulating HLA-specific memory B cells predict high risk of humoral rejection in kidney transplantation

Lúcia

Luque

Crespo

et al. 2015

Kidney International

104

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“…280,281 An immunovigilance registry of allo-(RBC, HLA, and HPA) immunized patients will assist selection of eligible patients (patient groups) for pre-emptive matching. 282 Such a registry can also stimulate collaborative studies that aim to reverse antibody production 283 and explore new treatment for severe complications of incompatible transfusions, transplants, or unborn children. 284 3.…”

Section: Evidence-based Indications Of Virtually All (Individualmentioning

confidence: 99%

The European Hematology Association Roadmap for European Hematology Research: a consensus document

et al. 2016

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T he European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

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“…A recent report using the ELISPOT assay and HLA class II biotinylated molecules has described the detection of HLA class II-specific memory cells (85) indicating this assay is a useful tool for identifying presensitization in the absence of circulating antibodies (86). …”

Section: Future Directionsmentioning

confidence: 99%

Detection of HLA Antibodies in Organ Transplant Recipients – Triumphs and Challenges of the Solid Phase Bead Assay

Tait

2016

Front. Immunol.

113

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This review outlines the development of human leukocyte antigen (HLA) antibody detection assays and their use in organ transplantation in both antibody screening and crossmatching. The development of sensitive solid phase assays such as the enzyme-linked immunosorbent assay technique, and in particular the bead-based technology has revolutionized this field over the last 10–15 years. This revolution however has created a new paradigm in clinical decision making with respect to the detection of low level pretransplant HLA sensitization and its clinical relevance. The relative sensitivities of the assays used are discussed and the relevance of conflicting inter-assay results. Each assay has its advantages and disadvantages and these are discussed. Over the last decade, the bead-based assay utilizing the Luminex® fluorocytometer instrument has become established as the “gold standard” for HLA antibody testing. However, there are still unresolved issues surrounding this technique, such as the presence of denatured HLA molecules on the beads which reveal cryptic epitopes and the issue of appropriate fluorescence cut off values for positivity. The assay has been modified to detect complement binding (CB) in addition to non-complement binding (NCB) HLA antibodies although the clinical relevance of the CB and NCB IgG isotypes is not fully resolved. The increase sensitivity of the Luminex® bead assay over the complement-dependent cytotoxicity crossmatch has permitted the concept of the “virtual crossmatch” whereby the crossmatch is predicted to a high degree of accuracy based on the HLA antibody specificities detected by the solid phase assay. Dialog between clinicians and laboratory staff on an individual patient basis is essential for correct clinical decision making based on HLA antibody results obtained by the various techniques.

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Quantification of HLA class II-specific memory B cells in HLA-sensitized individuals

Cited by 34 publications

References 31 publications

Preformed circulating HLA-specific memory B cells predict high risk of humoral rejection in kidney transplantation

Preformed circulating HLA-specific memory B cells predict high risk of humoral rejection in kidney transplantation

The European Hematology Association Roadmap for European Hematology Research: a consensus document

Detection of HLA Antibodies in Organ Transplant Recipients – Triumphs and Challenges of the Solid Phase Bead Assay

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