Dominant immune response to HLA‐B57/B58 molecules after platelet transfusion

Coombs, Justine; Hassen, Latifa Ben; Leclerc, Mathieu; Tamagne, Marie; Pannetier, Louise; Khelfa, Mehdi; Delorme, Adèle; Bocquet, Thibaut; Maury, Sébastien; Ansart‐Pirenne, Hélène; Vingert, Benoît

doi:10.1111/trf.16116

Cited by 4 publications

(7 citation statements)

References 18 publications

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“…Differences in the expression of HLA‐ABC or HLA‐A2, HLA‐B7, and HLA‐B57 would indicate a difference in haplotype expression profile potentially accounting for variable immunogenicity. HLA‐B57 was not markedly more strongly expressed on the surface of the cells studied, whereas we showed, in a previous retrospective study, that a high proportion of polytransfused patients develop anti‐HLA‐B57 6 . Other HLA molecules may be overexpressed.…”

Section: Discussioncontrasting

confidence: 53%

“…HLA-B57 was not markedly more strongly expressed on the surface of the cells studied, whereas we showed, in a previous retrospective study, that a high proportion of polytransfused patients develop anti-HLA-B57. 6 Other HLA molecules may be overexpressed. Significant interindividual variation was observed for HLA-B8, -B12, and -B35 expression on the surface of PLTs.…”

Section: Discussionmentioning

confidence: 99%

“…5 We showed, in a previous retrospective study, that a high proportion of multiply transfused patients develop anti-HLA-B57. 6 One hypothesis potentially accounting for this immunogenicity is the stronger expression of this HLA molecule than of other HLA molecules.…”

Section: Introductionmentioning

confidence: 99%

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HLA molecule expression on the surface of cells and microparticles in platelet concentrates

et al. 2020

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Background Platelet (PLT) transfusions are an essential treatment for bleeding disorders. However, immunologic complications can occur, including alloantibody production against Class I HLA molecules. The principal source of HLA molecules in PLT concentrates (PCs) is the PLTs themselves. However, extracellular microparticles (MPs) present in PCs may express HLA molecules. Study Design and Methods We used nanoscale flow cytometry to explore the expression of HLA‐A2, HLA‐B7, and HLA‐B57 on the surface of cells, PLT‐derived MPs (PMPs), lymphocyte‐derived MPs (LMPs), and monocyte‐derived MPs (MMPs) present in PCs. Expression was studied during 7 days of storage. Results Platelets were not the only source of HLA molecules in PCs. HLA molecules were present on PMPs, LMPs, and MMPs. The level of HLA Class I molecule expression varied between haplotypes and MPs of different origins and during storage. Conclusion Platelets or residual cells remaining after leukoreduction are not the only source of HLA Class I molecules in PCs, highlighting the contribution of MPs to alloimmunization mechanisms. These data may be relevant for the development of new transfusion guidelines.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

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HLA molecule expression on the surface of cells and microparticles in platelet concentrates

et al. 2020

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“…We tested this hypothesis by determining the levels of CD27 + MPs in PCs. CD27 plays an important role in the regulation of CD4 + TL responses and CD4 + functions during alloimmunization ( 25 – 27 ). We therefore studied the interaction of CD27-expressing MPs with CD4 + TLs and its functional effects.…”

Section: Introductionmentioning

confidence: 99%

CD27+ microparticle interactions and immunoregulation of CD4+ T lymphocytes

et al. 2023

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IntroductionAplasia and hematological malignancies are treated with platelet transfusions, which can have major immunomodulatory effects. Platelet concentrates (PCs) contain many immunomodulatory elements, including the platelets themselves, residual leukocytes, extracellular vesicles, such as microparticles (MPs), cytokines and other soluble elements. Two of these components, MPs and a soluble form of CD27 (sCD27), have been shown to play a particularly important role in immune system modulation. The loss of CD27 expression is an irreversible marker of terminal effector CD3+ T-lymphocyte (TL) differentiation, and the CD27+ MPs present in PCs may maintain CD27 expression on the surface of TLs, and, thus, the activation of these cells.MethodsIn this study, we phenotyped the CD27-expressing MPs present in PCs by microscale flow cytometry and investigated the interaction of these particles with CD4+ TLs. We cocultured MPs and PBMCs and determined the origin of the CD27 expressed on the surface of CD4+ TLs with the aid of two fluorochromes (BV510 for CD27 originating from MPs and BV786 for cellular CD27).ResultsWe showed that the binding of CD27- expressing MPs involved the CD70 molecule, which was also present on these MPs. Finally, the maintenance of CD27 expression on the surface of TLs by sorted CD27+ MPs led to activation levels lower than those observed with other types of MPs.DiscussionThese results for CD27-expressing MPs and their CD70-mediated targeting open up new possibilities for immunotherapy based on the use of MPs to maintain a phenotype or to target immune cells, for example. Moreover, decreasing the levels of CD27-expressing MPs in transfused platelets might also increase the chances of success for anti-CD27 monoclonal immunotherapy.

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“…In a first study with patients with hematologic malignancies, we showed that these anti-HLA specific CD4 + T responses are present in alloimmunized patients ( 7 ). Regardless of the antigen studied, these CD4 + T-cell responses had similar, rather monofunctional profiles different from more conventional responses ( e.g.…”

Section: Introductionmentioning

confidence: 99%

Divergent CD4+ T-cell profiles are associated with anti-HLA alloimmunization status in platelet-transfused AML patients

Khelfa,

Leclerc,

Kerbrat

et al. 2023

Front. Immunol.

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IntroductionAcute myeloid leukemia (AML) is one of the commonest hematologic disorders. Due to the high frequency of disease- or treatment-related thrombocytopenia, AML requires treatment with multiple platelet transfusions, which can trigger a humoral response directed against platelets. Some, but not all, AML patients develop an anti-HLA immune response after multiple transfusions. We therefore hypothesized that different immune activation profiles might be associated with anti-HLA alloimmunization status.MethodsWe tested this hypothesis, by analyzing CD4+ T lymphocyte (TL) subsets and their immune control molecules in flow cytometry and single-cell multi-omics.ResultsA comparison of immunological status between anti-HLA alloimmunized and non-alloimmunized AML patients identified differences in the phenotype and function of CD4+ TLs. CD4+ TLs from alloimmunized patients displayed features of immune activation, with higher levels of CD40 and OX40 than the cells of healthy donors. However, the most notable differences were observed in non-alloimmunized patients. These patients had lower levels of CD40 and OX40 than alloimmunized patients and higher levels of PD1. Moreover, the Treg compartment of non-alloimmunized patients was larger and more functional than that in alloimmunized patients. These results were supported by a multi-omics analysis of immune response molecules in conventional CD4+ TLs, Tfh circulating cells, and Tregs.DiscussionOur results thus reveal divergent CD4+ TL characteristics correlated with anti-HLA alloimmunization status in transfused AML patients. These differences, characterizing CD4+ TLs independently of any specific antigen, should be taken into account when considering the immune responses of patients to infections, vaccinations, or transplantations.

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Dominant immune response to HLA‐B57/B58 molecules after platelet transfusion

Cited by 4 publications

References 18 publications

HLA molecule expression on the surface of cells and microparticles in platelet concentrates

HLA molecule expression on the surface of cells and microparticles in platelet concentrates

CD27+ microparticle interactions and immunoregulation of CD4+ T lymphocytes

Divergent CD4+ T-cell profiles are associated with anti-HLA alloimmunization status in platelet-transfused AML patients

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