Neonatal isoimmune thrombocytopenia caused by type I CD36 deficiency having novel splicing isoforms of the <i>CD36</i> gene

Taketani, Takeshi; Ito, K.; Mishima, Seiji; Kanai, Rie; Uchiyama, Atsushi; Hirata, Yasushi; Kumakura, Shunichi; Ishikura, Hiroto; Yamaguchi, Seiji

doi:10.1111/j.1600-0609.2008.01093.x

Cited by 13 publications

(22 citation statements)

References 25 publications

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“…28 Interestingly, variable clinical pictures of FNAIT mediated by anti-CD36 isoantibodies, including mild and severe thrombocytopenia, hydrops fetalis, and recurrent abortions, have been observed. [9][10][11][12][13]29 However, the precise mechanism of this phenomenon is not known.…”

Section: Discussionmentioning

confidence: 99%

“…6 The clinical importance of anti-CD36 isoantibodies in the development of FNAIT has been reported in different populations. [9][10][11][12][13] Currently, the antigen-capture assay represents the gold standard for detecting platelet antibodies. 14 With this assay, platelet antigens captured by mouse monoclonal antibody are used as the target for platelet antibodies.…”

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confidence: 99%

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Fetal/neonatal alloimmune thrombocytopenia due to anti‐CD36 antibodies: antibody evaluations by CD36‐transfected cell lines

Lin

Lee

et al. 2017

Transfusion

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BACKGROUND: Isoantibodies against CD36 (platelet glycoprotein 4), developed in Type I CD36-deficient mothers are frequently reported as the cause of fetal/ neonatal alloimmune thrombocytopenia in the Asian population. Therefore, further detailed characterization of anti-CD36-mediated fetal/neonatal alloimmune thrombocytopenia is warranted. Here, we report the characterization of a patient with fetal/neonatal alloimmune thrombocytopenia in a Taiwanese family caused by anti-CD36 isoantibodies using a novel antigen-capture method. STUDY DESIGN AND METHODS:Platelets and monocytes were analyzed for CD36 expression by flow cytometry. Sequencing analysis of the CD36 gene was performed to identify the mutation underlying the CD36 deficiency. Stable transfected human embryonic kidney HEK293 cells expressing recombinant CD36 were established. These cells were used for the characterization of anti-CD36 isoantibodies by flow cytometry, immunoprecipitation, and antigen-capture assay. RESULTS:Flow cytometry analysis revealed a total absence of CD36 on both platelets and monocytes of the mother (Type I CD36-deficient) caused by heterozygous deletions of the CD36 gene (332_333delCA and c.1254 1 6_1254 1 11delTATTTG). Analysis of maternal serum with CD36-transfected HEK293 cells by flow cytometry, immunoprecipitation, and antigen-capture assay demonstrated the presence of anti-CD36 isoantibodies in maternal serum. Interestingly, this antibody could not be detected by the monoclonal antibody immobilization of platelet antigens assay when anti-CD36 monoclonal antibody (clone FA6-152) was used as the capture antibody.CONCLUSION: This case reemphasizes the role of anti-CD36 isoantibodies on the pathomechanism of fetal/ neonatal alloimmune thrombocytopenia. The fact that the monoclonal antibody immobilization of platelet antigens assay does not seem to be reliable for the identification of all anti-CD36 antibodies indicates that screening of anti-CD36 isoantibodies by a monoclonal antibody-independent method, as presented here, should be considered. Fetal/neonatal alloimmune thrombocytopenia (FNAIT), which occurs in from 1 of 800 to 1 of 1000 live births, is the most common cause of severe thrombocytopenia and intracranial hemorrhage in the fetus and in term newborns.1,2 FNAIT is caused by maternal antibodies, which recognize paternalderived alloantigens on fetal platelets, leading to platelet destruction. In Caucasians, more than 75% of FNAIT cases are induced by alloantibodies against human platelet antigen-1a (HPA-1a), 3,4 whereas the most common antibodies causing FNAIT in Japanese are anti-HPA-4b alloantibodies. The clinical importance of anti-CD36 isoantibodies in the development of FNAIT has been reported in different populations.9-13 Currently, the antigen-capture assay represents the gold standard for detecting platelet antibodies. 14 With this assay, platelet antigens captured by mouse monoclonal antibody are used as the target for platelet antibodies. Unfortunately, this approach does not seem to be reliable for the identi...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Fetal/neonatal alloimmune thrombocytopenia due to anti‐CD36 antibodies: antibody evaluations by CD36‐transfected cell lines

Lin

Lee

et al. 2017

Transfusion

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“…In the Chinese population, the frequency of type I was found to be around 0Á5% [12,17]. Although the overall frequency of immunization against CD36 is not known yet, several PTR and FNAIT cases have been recently reported in the Chinese population [12,18].…”

Section: Discussionmentioning

confidence: 99%

CD36 deficiency among South‐East Asian populations

Xia

et al. 2016

ISBT Science Series

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Immune‐mediated thrombocytopenia is commonly caused by platelet‐reactive antibodies mostly against polymorphic structures residing on platelet glycoproteins such as human leucocyte antigen and human platelet antigen (HLA class I and HPA). In the Japanese population, some individuals do not express CD36 (CD36null also known as Naka) on the cell surface. Immunization of these individuals can lead to the development of CD36 isoantibodies (anti‐Naka) which play a role in the mechanism of platelet transfusion refractoriness, post‐transfusion purpura and fetal/neonatal alloimmune thrombocytopenia. Until today, however, little is known about the clinical relevance of CD36 deficiency and CD36 isoantibodies among other South‐East Asian populations. Therefore, multinational study was organised under the aegis of the ISBT to study the distribution of CD36 deficiency in this region.

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“…In addition to HPA antigens, antibodies against CD36 glycoprotein a member of class B scavenger receptor family [58] is also implicated in the causal of FNAIT. A case study reported, maternal deficiency in expression of CD36 protein lead to maternal immunization against CD36 protein (anti-NAK) [59]. The clinical impact of NAIT is related with maternal immunization against CD36 is analogous to that observed in infants affected by HPA specific antibodies [60].…”

Section: Foetal/neonatal Alloimmune Thrombocytopenia (Fnait)mentioning

confidence: 94%

Alloimmunization and Role of HLA in Pregnancy

Singh¹,

Rajak²,

Rajadhyaksha³

2019

Complications of Pregnancy

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Alloimmunization also known as isoimmunization, during pregnancy is the production of IgG antibodies by the mother against the paternally inherited antigens (IPA) in the foetus/newborn. The alloimmunization during pregnancy leads to various alloimmune disorders, such as, haemolytic disease of the foetus and newborn (HDFN), neonatal alloimmune neutropenia (NAN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT) due to the production of maternal alloantibodies against the red blood cell antigen, neutrophils and platelets cell antigens, respectively. Recent studies suggest that maternal anti-HLA class I alloantibodies may also be the cause of FNAIT in addition to antibodies against platelet antigens. On the contrary, studies have also suggested that HLA-C, a classical HLA class I molecule, and HLA-G, a nonclassical HLA molecule, play an important role in placentation and modulation of the maternal immune system during pregnancy, respectively, and thereby leading to acceptance of the semi allogeneic fetus. So far most of the studies have discussed alloimmunization in pregnancy relating to Rh antigen. Thus, in this chapter an attempt has been made to discuss alloimmunization in pregnancy caused because of maternal alloantibody against HLA antigen and its role in immune modulation during pregnancy.

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Neonatal isoimmune thrombocytopenia caused by type I CD36 deficiency having novel splicing isoforms of the CD36 gene

Cited by 13 publications

References 25 publications

Fetal/neonatal alloimmune thrombocytopenia due to anti‐CD36 antibodies: antibody evaluations by CD36‐transfected cell lines

Fetal/neonatal alloimmune thrombocytopenia due to anti‐CD36 antibodies: antibody evaluations by CD36‐transfected cell lines

CD36 deficiency among South‐East Asian populations

Alloimmunization and Role of HLA in Pregnancy

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