HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management

Pavenski, Katerina; Freedman, John; Semple, John W.

doi:10.1111/j.1399-0039.2012.01852.x

Cited by 133 publications

(163 citation statements)

References 64 publications

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“…macrophages) of the reticuloendothelial system. These initial uptake mechanisms allow for recipient splenic macrophages and DCs to potentially act as APC that stimulate the host's adaptive immune system and the eventual production of IgG antidonor antibodies [75].…”

Section: Hla and Transfusionmentioning

confidence: 99%

Clinical Role of Human Leukocyte Antigen in Health and Disease

2015

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Most of the genes in the major histocompatibility complex (MHC) region express high polymorphism that is fundamental for their function. The most important function of human leukocyte antigen (HLA) molecule is in the induction, regulation of immune responses and the selection of the T cell repertoire. A clinician's attention is normally drawn to a system only when it malfunctions. The HLA system is no exception in this regard, but in contrast to other systems, it also arouses interest when it functions well -too well, in fact. Population studies carried out over the last several decades have identified a long list of human diseases that are significantly more common among individuals that carry particular HLA alleles including inflammatory, autoimmune and malignant disorders. HLAdisease association is the name of this phenomenon, and the mechanism underlying is still a subject of hot debate. Social behaviours are affected by HLA genes and preference for HLA disparate mates may provide 'good genes' for an individual's offspring. Also, certain HLA genes may be associated with shorter life and others with longer lifespan, but the effects depend both on the genetic background and on the environmental conditions. The following is a general overview of the important functional aspects of HLA in health and diseases.

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Section: Hla and Transfusionmentioning

confidence: 99%

Clinical Role of Human Leukocyte Antigen in Health and Disease

2015

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“…refractoriness conditions after PLT transfusion (4)(5)(6)(7). Currently, the management of patients suffering of PLT transfusion refractoriness is based on the provision of HLA-matched or cross-matched PLTs.…”

mentioning

confidence: 99%

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Börger

Eicke

Wolf

et al. 2016

Mol Med

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Platelet (PLT) transfusion is indispensable to maintain homeostasis in thrombocytopenic patients. However, PLT transfusion refractoriness is a common life-threatening condition observed in multitransfused patients. The most frequent immune cause for PLT transfusion refractoriness is the presence of alloantibodies specific for human leukocyte antigen (HLA) class I epitopes. Here, we have silenced the expression of HLA class I to generate a stable HLA-universal induced pluripotent stem cell (iPSC) line that can be used as a renewable cell source for the generation of low immunogenic cell products. The expression of HLA class I was silenced by up to 82% and remained stable during iPSC cultivation. In this study, we have focused on the generation of megakaryocytes (MK) and PLTs from a HLA-universal iPSC source under feeder-and xeno-free conditions. On d 19, differentiation rates of MKs and PLTs with means of 58% and 76% were observed, respectively. HLA-universal iPSC-derived MKs showed polyploidy with DNA contents higher than 4n and formed proPLTs. Importantly, differentiated MKs remained silenced for HLA class I expression. HLA-universal MKs produced functional PLTs. Notably, iPSC-derived HLA-universal MKs were capable to escape antibody-mediated complement-and cellular-dependent cytotoxicity. Furthermore, HLA-universal MKs were able to produce PLTs after in vivo transfusion in a mouse model indicating that they might be used as an alternative to PLT transfusion. Thus, in vitro produced low immunogenic MKs and PLTs may become an alternative to PLT donation in PLT-based therapies and an important component in the management of severe alloimmunized patients.

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“…Even if the antibody against-HLA alloimmunization is more frequent than the antibody against-HPA [7], in our case the presence of platelet-specific antigens is not ruled out by this major thrombocytopenia, especially patients with anti-HLA alloimmunization more frequently develop anti-HPA antibodies [2].…”

Section: Commentsmentioning

confidence: 90%

Clinical Case: About a Probable Case of Post-Transfusion Purpura in a Homozygous Sickle Cell

Irène¹,

Jocia²,

Sonia³

et al. 2017

CRCM

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Alloimmunization to platelet antigens exposes to a serious immunological incident. We report a probable case of a post-transfusion purpura from homozygous sickle cell child alloimmunized against platelet antigen. We detail the challenges of alloantibody identification and transfusion management. These challenges are due to the lack of laboratory techniques for typing HLA and HPA system and the use of leukocyte-depleted (filtered) blood products.

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HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management

Cited by 133 publications

References 64 publications

Clinical Role of Human Leukocyte Antigen in Health and Disease

Clinical Role of Human Leukocyte Antigen in Health and Disease

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Clinical Case: About a Probable Case of Post-Transfusion Purpura in a Homozygous Sickle Cell

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