Max(a), a new low-frequency platelet-specific antigen localized on glycoprotein IIb, is associated with neonatal alloimmune thrombocytopenia

Noris, Patrizia; Şimşek, Suat; Bruijne-Admiraal, L. G. De; Porcelijn, Leendert; Huiskes, Elly; Vlist, Gert J. van der; Leeuwen, E. F. Van; Schoot, C. Ellen van der; Borne, A. E. G. K. Von Dem

doi:10.1182/blood.v86.3.1019.1019

Cited by 72 publications

(48 citation statements)

References 13 publications

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“…PCR products were digested by restricted endonuclease: Hpa II for HPA‐1 (9) and the mutation associated with HPA‐1 (10) showed by the presence of an additional 153 bp fragment in the HPA‐1b PCR‐RFLP pattern; Sfa NI for HPA‐2 (9); Fok 1 for HPA‐3 (9); Bst NI for HPA‐9w (11); HPA‐15 (12) and GPIIb IVS21(‐7) associated with HPA‐3b (13); Mnl1 for HPA‐5 (9) and HpyCH4V for HPA‐4.…”

Section: Methodsmentioning

confidence: 99%

Human platelet antigen allele frequencies in different Algerian populations

et al. 2010

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The frequencies of human platelet antigens (HPAs) vary between different populations and are a major determinant for the prevalence of HPA alloimmunization and its clinically associated entities. No report on HPA prevalence has previously been published for the Algerian populations which are ethnically diverse. The aim of this study was to determine the HPA allele frequencies in Algerian populations and to identify situations of incompatibility possibly leading to alloimmunization. A total of 485 healthy volunteer Algerian blood donors from different regions and representing different ethnic groups were included. HPA genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or polymerase chain reaction-sequence specific primer (PCR-SSP). The HPA-1 allele frequencies were close to the frequencies found in Caucasian populations. The presence of the molecule human leukocyte antigen (HLA)-DRB3*0101 (17.9%) increases the risk of alloimmunization. We observed an increase in the frequency of homozygous HPA-5b, particularly in the population of Annaba (7.61%) and the Mzab population (5.13%). The allele frequency HPA-2b (0.193-0.147) was similar to that seen in Sub-Saharan African populations. The high frequency of homozygotic HPA-2b (Kabyle 5%; Mzab 2.44% and Annaba 2.19%) could increase the risk of alloimmunization. GPIIb A(k) mutation (2614C>A) was found in these populations. This study is the first to report on HPA allele frequencies in Algerian populations. High allele frequencies were observed for HPA-1b (0.209-0.112), HPA-3b (0.411-0.312) and HPA-5b (0.217-0.087), leading to a high risk of alloimmunization in this population, especially the Mzab and the population of Annaba. Our results could have some impact in the diagnosis, prevention and treatment of alloimmune thrombocytopenia.

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Section: Methodsmentioning

confidence: 99%

Human platelet antigen allele frequencies in different Algerian populations

et al. 2010

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“…The human platelet alloantigen 9bw (HPA‐9bw, Max a ) is an epitope of GPIIb and differs by 2602G>A single nucleotide polymorphism (SNP), resulting in a Val/Met substitution at amino acid 837 (Noris et al , 1995). Alloantibodies against Max a are involved in the development of neonatal alloimmune thrombocytopenia (NAIT) (Kaplan et al , 2005; Raj et al , 2009).…”

Section: Genotype and Allelic Frequencies Of Hpa‐9 And Hpa‐3 In Brazimentioning

confidence: 99%

HPA-9 and HPA-3 allelic frequencies in Brazilian blood donors and Amazon Indians

Kuniyoshi

Chiba

Filho

et al. 2010

Transfusion Medicine

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The human platelet alloantigen 9bw (HPA-9bw, Max a ) is an epitope of GPIIb and differs by 2602G>A single nucleotide polymorphism (SNP), resulting in a Val/Met substitution at amino acid 837 (Noris et al., 1995). Alloantibodies against Max a are involved in the development of neonatal alloimmune thrombocytopenia (NAIT) (Kaplan et al., 2005;Raj et al., 2009). The frequency of HPA-9b allele is low at 0·003 in the Dutch population (Noris et al., 1995), 0·002 in United States (Peterson et al., 2005) and 0·0 in China (Xu et al., 2009). However, Peterson and coworkers found six cases involving alloantibodies anti-HPA-9bw among 217 cases not resolved on NAIT, suggesting that HPA-9bw may be the third most important trigger for NAIT, after HPA-1a and HPA-5b (Peterson et al., 2005). In such studies, HPA-3b allele was present in all individuals with HPA-9b allele.The HPA frequencies vary among distinct populations. In the literature, there are no data for the allelic frequencies of HPA-9 system in the South American population. In this study, we used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the HPA-9 and HPA-3 allelic frequencies in Brazilian blood donors and Amazon Indians. The study was approved by the University Research Ethics Committee (CEP 0793/08). Blood samples from 1073 unrelated Brazilian blood donors and 120 Amazon Indians (Xikrin Kayapo Indians) were collected. DNA was isolated using a commercial kit (QIAamp DNA Blood mini kit, Qiagen, Hilden, Germany) and genotyped by PCR-RFLP using BstNI restriction enzyme for HPA-9 and Fok I for HPA-3. Control samples were used and we performed the sequencing in selected samples containing the SNPs to confirm the region studied.The results of genotype and allelic frequencies of HPA-9 and HPA-3 systems in Brazilian blood donors and Xikrin Indians are shown in Table 1. We found that the frequencies of the genotypes HPA-9a/9a, 9a/9b and 9b/9b were 99·72, 0·28 and 0% in Brazilian blood donors and 100, 0 and 0% in Amazon Indians, respectively. HPA-3a/3a, 3a/3b and 3b/3b had frequencies of 41·29, 46·50 and 12·21% in Brazilian blood donors and 41·67, 52·50 and 5·83% in Amazon Indians. The analysis by statistical χ 2 with significance level of 0·05 showed that no statistically significant differences were found regarding the HPA-9a, HPA-9b, HPA-3a and HPA-3b allelic frequencies between Brazilian blood donors (0·999, 0·001, 0·645, 0·355) and Xikrin Indians (1·0, 0·0, 0·679, 0·321). Using sequencing methods for selected samples we confirmed the corresponding SNPs; however, we did not find any other polymorphisms such as those described by the study of Hallé and coworkers in which they found mutations on GPIIb exon 26 (2614C>A and 2645C>T) and intron 26 (IVS26+89G>A) (Hallé et al., 2008). All individuals carrying the HPA-9b allele also had the HPA-3b allele.The HPA-9 allelic frequencies found in Brazilians are quite similar to those reported by studies performed with Dutch, North American and Chinese individuals as mentioned e...

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“…Low‐frequency PLT alloantigens shown to cause maternal immunization leading to NAIT include those now designated HPA‐4b; 24,25 HPA‐6bw; 26,27 HPA‐7bw; 28 HPA‐8bw; 29 HPA‐9bw; 30 HPA‐10bw; 31 HPA‐11bw; 32 HPA‐12bw; 33 HPA‐13bw; 34 HPA‐14bw; 35 HPA‐16bw; 36 HPA‐17bw; 37 HPA‐18bw; 38 HPA‐19bw, ‐20bw, and ‐21bw; 10 HPA‐22bw; 39 Swi; 13 and Cab2 14 . The two new antigens described here bring the total to 21.…”

Section: Discussionmentioning

confidence: 99%

“…The two new antigens described here bring the total to 21. The most important of these antigens from a clinical standpoint appears to be HPA‐9bw, found on PLT GPIIb of approximately 1 in 400 persons of Northern European ancestry 18,30,40 . Fourteen cases of NAIT caused by HPA‐9bw antibodies have now been reported, many of which were severe and five of which were complicated by intracranial hemorrhage 18,30,40 .…”

Section: Discussionmentioning

confidence: 99%

“…The most important of these antigens from a clinical standpoint appears to be HPA‐9bw, found on PLT GPIIb of approximately 1 in 400 persons of Northern European ancestry 18,30,40 . Fourteen cases of NAIT caused by HPA‐9bw antibodies have now been reported, many of which were severe and five of which were complicated by intracranial hemorrhage 18,30,40 . Other reports of NAIT caused by maternal immunization against low‐frequency antigens involved single cases with the exception of HPA‐4b, 24,25 HPA‐6bw, 26,27,41 HPA‐8bw, 29,41 HPA‐10bw, 31,41 HPA‐11bw, 9,32 and HPA‐13bw 9,34,42 …”

Section: Discussionmentioning

confidence: 99%

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New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia

et al. 2011

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BACKGROUND Maternal immunization against low-frequency, platelet (PLT)-specific antigens is being recognized with increasing frequency as a cause of neonatal alloimmune thrombocytopenia (NAIT). STUDY DESIGN AND METHODS Serologic and molecular studies were performed on PLTs and DNA from two families in which an infant was born with severe thrombocytopenia not attributable to maternal immunization against known PLT-specific alloantigens. RESULTS Antibodies reactive only with paternal PLTs were identified in each mother using flow cytometry and solid-phase assays. Unique mutations encoding amino acid substitutions K164T in glycoprotein (GP)IIb (Case 1) and R622W in GPIIIa (Case 2) were identified in paternal DNA and in DNA from the affected infants. Each maternal antibody recognized recombinant GPIIb/IIIa mutated to contain the polymorphisms identified in the corresponding father. None of 100 unselected normal subjects possessed these paternal mutations. CONCLUSIONS Severe NAIT observed in the affected infants was caused by maternal immunization against previously unrecognized, low-frequency antigens created by amino acid substitutions in GPIIb/IIIa (αIIb/β3 integrin). A search should be conducted for novel paternal antigens in cases of apparent NAIT not explained on the basis of maternal-fetal incompatibility for known human PLT antigens.

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Max(a), a new low-frequency platelet-specific antigen localized on glycoprotein IIb, is associated with neonatal alloimmune thrombocytopenia

Cited by 72 publications

References 13 publications

Human platelet antigen allele frequencies in different Algerian populations

Human platelet antigen allele frequencies in different Algerian populations

HPA-9 and HPA-3 allelic frequencies in Brazilian blood donors and Amazon Indians

New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia

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