A New Platelet-Specific Antigen, Naka, Involved in the
Refractoriness of HLA-Matched Platelet Transfusion

Ikeda, Hisami; Mitani, Takako; Ohnuma, Miki; Haga, Hiroshi; Ohtzuka, Sayuri; Kato, Toshiaki; Nakase, Toshie; Sekiguchi, Sadayoshi

doi:10.1159/000461044

Cited by 63 publications

(84 citation statements)

References 9 publications

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“…42 CD36 deficiency was first described in 1989 by Ikeda et al 43 in a case that was refractory to platelet transfusion due to the presence of a new anti-platelet antibody, named anti-Naka. Yamamoto et al 44 later showed that the Nak a epitope is part of the CD36 molecular structure and that in the patients mentioned above this protein was not well expressed.…”

Section: Discussionmentioning

confidence: 99%

Altered immunophenotypic features of peripheral blood platelets in myelodysplastic syndromes

Sandes¹,

Yamamoto²,

Matarraz³

et al. 2012

Haematologica

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BackgroundMultiparameter flow cytometric analysis of bone marrow and peripheral blood cells has proven to be of help in the diagnostic workup of myelodysplastic syndromes. However, the usefulness of flow cytometry for the detection of megakaryocytic and platelet dysplasia has not yet been investigated. The aim of this pilot study was to evaluate by flow cytometry the diagnostic and prognostic value of platelet dysplasia in myelodysplastic syndromes. Design and MethodsWe investigated the pattern of expression of distinct surface glycoproteins on peripheral blood platelets from a series of 44 myelodysplastic syndrome patients, 20 healthy subjects and 19 patients with platelet alterations associated to disease conditions other than myelodysplastic syndromes. Quantitative expression of CD31, CD34, CD36, CD41a, CD41b, CD42a, CD42b and CD61 glycoproteins together with the PAC-1, CD62-P, fibrinogen and CD63 platelet activation-associated markers and platelet light scatter properties were systematically evaluated. ResultsOverall, flow cytometry identified multiple immunophenotypic abnormalities on platelets of myelodysplastic syndrome patients, including altered light scatter characteristics, over-and under expression of specific platelet glycoproteins and asynchronous expression of CD34; decreased expression of CD36 (n=5), CD42a (n=1) and CD61 (n=2), together with reactivity for CD34 (n=1) were only observed among myelodysplastic syndrome cases, while other alterations were also found in other platelet disorders. Based on the overall platelet alterations detected for each patient, an immunophenotypic score was built which identified a subgroup of myelodysplastic syndrome patients with a high rate of moderate to severe alterations (score>1.5; n=16) who more frequently showed thrombocytopenia, megakaryocytic dysplasia and high-risk disease, together with a shorter overall survival. ConclusionsOur results show the presence of altered phenotypes by flow cytometry on platelets from around half of the myelodysplastic syndrome patients studied. If confirmed in larger series of patients, these findings may help refine the diagnostic and prognostic assessment of this group of disorders.

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Section: Discussionmentioning

confidence: 99%

Altered immunophenotypic features of peripheral blood platelets in myelodysplastic syndromes

Sandes¹,

Yamamoto²,

Matarraz³

et al. 2012

Haematologica

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“…However, except for the index case, 25 all Nak'-negative individuals thus far identified have been self-selected as young, healthy blood donors.…”

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confidence: 99%

“…23 - 24 The Nak a -negative phenotype occurs with a high incidence (=3%) in Japanese blood donors 25 but occurs in only 0.2% of US blood donors. 1 Because they lack detectable GPIV, 2324 the platelets of Nak'-negative individuals have been used to study the role of GPIV in platelet function.…”

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Platelet activation results in a redistribution of glycoprotein IV (CD36).

Michelson

Wencel-Drake

Kestin

et al. 1994

Arterioscler Thromb

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To investigate the possibility that thrombin and/or other platelet activators change the platelet surface expression of glycoprotein IV (GPIV, CD36), we used a panel of five GPIV-specific monoclonal antibodies (OKM5, 5F1, FA6-152, 8A6, and F13) directed against different epitopes. All these antibodies bound to resting platelets in a concentration-dependent and saturable manner, as determined by flow cytometry of washed platelets. Thrombin (1 U/mL) induced an approximately twofold increase in the platelet surface binding of each of these monoclonal antibodies. Immunofluorescence microscopy demonstrated an internal pool of GPIV that, after thrombin stimulation, redistributed to the platelet surface. In a whole-blood fiow-cytometric assay, a-thrombin and the G lycoprotein (GP) IV, also known as GPIIIb and CD36, is present on the surface of human platelets and other cells, including endothelial cells, monocytes, erythrocytes, and megakaryocytes. 1 GPIV is composed of a single highly glycosylated polypeptide chain with an apparent molecular mass of 88 kD.2 - 3 The structure of GPIV has several homologies with a recently described lysosomal integral membrane protein (LIMP II), suggesting that GPIV and LIMP II belong to a new gene family. 4 There are between 12 000 and 25 000 copies of GPIV on the platelet surface. - 6GPIV is very resistant to protease digestion. 78 GPIV may play a number of important roles in platelet function and pathophysiology. First, GPIV has been reported to be a collagen receptor involved in the initial phase of platelet-collagen adhesion. 910 Second, GPIV has been reported to be a receptor for thrombospondin 3 ' 11 and may therefore have a role in thrombospondin-dependent platelet aggregation 1213 and thrombospondin-dependent platelet-monocyte adhesion. 14 Third, platelet GPIV is physically associated with the fyn, lyn, and yes protein tyrosine kinases and may be involved in platelet signal transduction.1 -15 Fourth, GPIV is a receptor for the adhesion of Plasmodium falciparumAniected erythrocytes. 1617 Fifth, GPIV may have a role in the pathophysiology of thrombotic thrombocytopenic purpura (TTP), because the plasma of a Received November 5, 1993; revision accepted April 26, 1994 The platelet-specific antigen Nak* is present on GPIV. 23- 24 The Nak a -negative phenotype occurs with a high incidence (=3%) in Japanese blood donors 25 but occurs in only 0.2% of US blood donors.1 Because they lack detectable GPIV, 2324 the platelets of Nak'-negative individuals have been used to study the role of GPIV in platelet function. Nak'-negative individuals show reduced adhesion to collagen in flowing whole blood. 10The lack of evidence of a hemostatic defect in Nak'-negative individuals suggests that binding of collagen to other proteins (eg, the GPIa-IIa complex 26 and GPVI 27 ) may be sufficient to avoid an overt bleeding diathesis. Thrombospondin binding to the platelets of Nak'-negative individuals appears to be normal, 2829 which calls into question the role of GPIV as a thrombospondin...

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“…Although we found that platelets from different individuals with different intrinsic expression of CD36 on their platelets produced similar effects on monocyte fluorescence according to platelet number, we studied samples from individuals without deficiencies (either type I or type II) in CD36 expression. Individuals with deficient expression, present at a higher prevalence in some populations, (18)(19)(20)(21)(22) are also of particular interest to investigators of CD36. Individuals with CD36 deficiency restricted to platelets (Type 2 CD36 deficiency), otherwise missed if platelet CD36 expression is not assessed, would not be expected to compete for reagent antibody.…”

Section: Discussionmentioning

confidence: 99%

When monocytes and platelets compete: The effect of platelet count on the flow cytometric measurement of monocyte CD36

Dzik

Cserti‐Gazdewich

Ssewanyana

et al. 2009

Cytometry Part B Clinical

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Background: Flow cytometric measurement of monocyte surface CD36 is relevant to several conditions including diabetes, cardiovascular disease, lipid disorders, platelet isoimmunization, and susceptibility to P falciparum malaria. CD36 is also strongly expressed on platelets where it is also known as platelet glycoprotein IV.Methods: Whole blood samples, containing identical monocyte concentrations, were adjusted to contain platelets ranging from 20,000/uL to 600,000/uL, were stained with fluorescent-labeled anti-CD36, and analyzed by flow cytometry.Results: CD36 median fluorescent intensity (MFI) observed on monocytes decreased as the platelet concentration in the sample increased with more than a 50% decline in monocyte MFI over the normal range of platelet values. The effect was not abolished by using larger volumes of monoclonal antibody and was observed with different clones of reagent anti-CD36. The findings were most consistent with competition by platelets for the CD36 reagent. Similar findings were observed with antibody to class I HLA. Under defined assay conditions, monocyte CD36 MFI declined with rising platelet concentration in a predictable fashion following an inverse linear relationship.Conclusions: Measurement of CD36 expression on monocytes by flow cytometry in whole blood samples is affected by the sample platelet count. When comparing the monocyte CD36 expression among different individuals, our approach can be used to adjust measured monocyte CD36 expression for the effect of the platelet concentration in the sample. Competition by platelets for monoclonal reagents may occur in other settings when whole blood assays are used and when the target antigen is strongly expressed on both platelets and leukocytes.

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A New Platelet-Specific Antigen, Naka, Involved in the Refractoriness of HLA-Matched Platelet Transfusion

Cited by 63 publications

References 9 publications

Altered immunophenotypic features of peripheral blood platelets in myelodysplastic syndromes

Altered immunophenotypic features of peripheral blood platelets in myelodysplastic syndromes

Platelet activation results in a redistribution of glycoprotein IV (CD36).

When monocytes and platelets compete: The effect of platelet count on the flow cytometric measurement of monocyte CD36

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