Maternal alloimmunization against the rare platelet‐specific antigen HPA‐9b (Max<sup>a</sup>) is an important cause of neonatal alloimmune thrombocytopenia

Peterson, Julie A.; Balthazor, S. M.; Curtis, Brian R.; McFarland, Janice G.; Aster, Richard H.

doi:10.1111/j.1537-2995.2005.00561.x

Cited by 61 publications

(78 citation statements)

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“…15,16 All constructs were validated by sequencing of cDNA incorporated into the expression vectors. CHO cells were cotransfected with chimeric GPIIb in the expression vector pcDNA3 with neomycin selection (Invitrogen) and nonmutated human GPIIIa in the expression vector pcDNA3.1 with zeocin selection with Fugene 6, using the manufacturer's suggested protocol.…”

Section: Expression Of Gpiib/iiia Constructs In Chinese Hamster Ovarymentioning

confidence: 99%

Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia

Bougie

Birenbaum

Rasmussen

et al. 2009

Blood

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Section: Expression Of Gpiib/iiia Constructs In Chinese Hamster Ovarymentioning

confidence: 99%

Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia

Bougie

Birenbaum

Rasmussen

et al. 2009

Blood

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“…Automated sequence analysis of polymerase chain reaction products was performed in both directions with the Big Dye Terminator version 3.1 Cycle Sequencing kit on an ABI 3130XL genetic analyzer (Applied Biosystems). 13 …”

Section: Dna Sequencingmentioning

confidence: 99%

The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution

Curtis

Cox

Sullivan

et al. 2010

Blood

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IntroductionThe leukocyte antigens 5a and 5b (now designated HNA-3b and HNA-3a) constitute a biallelic antigen system identified by van Leeuwen et al in 1964 using antibodies from multiparous women that agglutinated leukocytes of normal persons. 1 Despite the passage of more than 40 years, molecular properties of the HNA-3 antigens have not been defined. Characterization of HNA-3a has become particularly important with the recognition that HNA-3a-specific antibodies are prone to cause severe, often fatal, transfusion-associated acute lung injury (TRALI). [2][3][4][5] Here, we provide evidence that HNA-3a is carried on choline transporter-like protein 2 (CTL2), a member of the choline transporter-like family of membrane glycoproteins, and that the antigen results from a single nucleotide polymorphism (SNP) in exon 7 of the CTL2 gene (SLC44A2) encoding R154 (HNA-3a) or Q154 (HNA-3b) in the first extracellular loop of the mature protein. Methods Antibodies and antibody detectionHNA-3a-specific antibodies were from donors implicated in TRALI reactions. 3,6 Isolation of neutrophils, T and B lymphocytes, and platelets from normal donor blood, detection of antibodies reactive with these cells by flow cytometry and agglutination, and immunoprecipitation of membrane proteins have been described previously. [7][8][9] SNP analysisGenotyping of DNA from 8 unrelated HNA-3a-negative persons was performed using the Human Genome-Wide SNP Array 6.0 (Affymetrix). Genotypes were assigned using Birdseed 2.0. 10 Quality control studies, including assessment of call rate, investigation of potential genetic relationships among samples, and examination of data to identify potential departures from expected levels of heterozygosity, were completed using plink. 11 Eigenstrat was used to assess geographic ancestry in combination with HapMap CEU, YRI, JPT, and CHB samples. 12 All samples had high call rates (Ͼ 98%) with high-quality genotype data. The 8 HNA-3a-negative persons appeared to be of recent European descent and were quite similar in ancestry to the HapMap CEU samples. Association studies were performed using the 8 HNA-3a-negative samples as cases and unrelated European samples from HapMap3 as controls, with significance assessed using 100 000 permutations; thus, the smallest possible P value in permutation analysis was P ϭ 1 ϫ 10 Ϫ6 . DNA sequencingGenomic DNA was amplified by the polymerase chain reaction using primers designed to amplify exon 7 of the CTL2 gene SLC44A2 (reference sequence National Center for Biotechnology Information database; www.ncbi.nlm.nih.gov/nucore/NM_001145056.1). Primer sequences are available on request. Automated sequence analysis of polymerase chain reaction products was performed in both directions with the Big Dye Terminator version 3.1 Cycle Sequencing kit on an ABI 3130XL genetic analyzer (Applied Biosystems). 13 Mass spectrometryHNA-3a-specific antibody was incubated with HNA-3a-positive leukocytes and subjected to immunoprecipitation. An Inside Blood analysis of this article appears at the fr...

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“…The frequency of all other HPA alloabs is too low to estimate a clear relationship between specificity and clinical consequence. Recent reports suggest that HPA-9w may be more important for FNAIT than previously suspected [16,17]. It will be interesting to study how the clinical presentation of HPA-9w and HPA-3 alloabs compare, since the underlying polymorphisms are located closely to each other.…”

Section: Alloimmune Thrombocytopenic Syndromesmentioning

confidence: 99%

Heterogeneity of Platelet Alloantigens and Alloantibodies: New Insights into Structure and Function

Socher

Kroll

2006

Transfus Med Hemother

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Human platelet alloantigens (HPAs) and their corresponding alloantibodies (alloabs) play an essential role in fetal and neonatal alloimmune thrombocytopenia, posttransfusion purpura and platelet transfusion refractoriness. Emerging genotyping methods (e.g. microarray technology) will allow an automated throughput for HPA typing of large donor cohorts in the near future. For the clinical diagnosis of alloimmune thrombocytopenia, however, the proof of pathogenic alloabs still remains a prerequisite. Nowadays, monoclonal antibody-based antigen capture assays are the state of the art in many laboratories. This technique seems to come up against limiting factors. In a certain number of cases that are highly suspicious for alloimmune thrombocytopenia, platelet-specific alloabs are not detectable. Current observations indicate that these alloabs are heterogeneous in terms of their alloantigenic determinants as well as the consequences on platelet function. This heterogeneity may correlate to the severe bleeding complications sometimes seen in patients with alloimmune thrombocytopenia. New insights on the role of pathogenic alloabs will help us to improve diagnostic and therapeutic approaches for the adequate treatment of affected patients.

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Maternal alloimmunization against the rare platelet‐specific antigen HPA‐9b (Max^a) is an important cause of neonatal alloimmune thrombocytopenia

Abstract: Maternal immunization against HPA-9b (Max(a)) is an important cause of NATP and should be considered in cases of apparent NATP not resolved on the basis of maternal-fetal incompatibility for "common" PLT antigens.

Cited by 61 publications

References 49 publications

Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia

Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia

The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution

Heterogeneity of Platelet Alloantigens and Alloantibodies: New Insights into Structure and Function

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Maternal alloimmunization against the rare platelet‐specific antigen HPA‐9b (Maxa) is an important cause of neonatal alloimmune thrombocytopenia

Abstract: Maternal immunization against HPA-9b (Max(a)) is an important cause of NATP and should be considered in cases of apparent NATP not resolved on the basis of maternal-fetal incompatibility for "common" PLT antigens.

Cited by 61 publications

References 49 publications

Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia

Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia

The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution

Heterogeneity of Platelet Alloantigens and Alloantibodies: New Insights into Structure and Function

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Maternal alloimmunization against the rare platelet‐specific antigen HPA‐9b (Max^a) is an important cause of neonatal alloimmune thrombocytopenia