Geno‐ and phenotyping and immunogenicity of HNA‐3

Reil, Angelika; Wesche, Jan; Greinacher, Andreas; Bux, Juergen

doi:10.1111/j.1537-2995.2010.02751.x

Cited by 58 publications

(81 citation statements)

References 21 publications

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“…In contrast, immunogenicity of HNA-3b seems to be much lower [82], and also the clinical effect of HNA-3b alloantibodies is less severe. …”

Section: Hna-3mentioning

confidence: 99%

“…5). The HNA-3a encoding allele was demonstrated in Caucasians with a frequency of 0.79, in African Americans with 0.93 and in Chinese with 0.74, and the respective HNA-3b-encoding alleles with 0.21, 0.07 and 0.26 [82,83,84]. An additional SLC44A2*451C>T exchange (rs147820753) affecting the amino acid next to Arg152 and inducing a Leu151Phe substitution impairs the HNA-3a epitope in a way that the induction of neutrophil agglutination by some HNA-3a-specific alloantibodies is diminished or even abrogated [85].…”

Section: Hna-3mentioning

confidence: 99%

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Molecular Genetics of the Human Neutrophil Antigens

Flesch

Reil²

2018

Transfus Med Hemother

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Background and Objective: Antibodies to human neutrophil antigens (HNAs) have been implicated in transfusion-related acute lung injury and allo- and autoimmune neutropenia. To date, five HNA systems are assigned, and during the last decades enormous efforts have been undertaken to identify the underlying genes and to characterize the antigens. This review of the literature will provide the current genetic, molecular and functional information on HNAs. Recent Findings: New information on alleles and antigens has been added to nearly each of the five HNA systems. HNA-1d has been added as the antithetical epitope to HNA-1c that is located on the glycoprotein encoded by FCGR3B*02 but not by FCGR3B. FCGR3B*04 and *05 now are included as new alleles. A CD177*787A>T substitution was demonstrated as the main reason for the HNA-2-negative phenotype on neutrophils. The target glycoprotein of HNA-3 antibodies could be identified as choline transporter-like protein 2 (CTL2) encoded by SLC44A2. The conformation sensitive epitope discriminates between arginine and glutamine at position 152 resulting in HNA-3a and HNA-3b. An additional Leu151Phe substitution can impair HNA-3a antibody binding. Recently an alloantibody against HNA-4b which discriminates from HNA-4a by an Arg61His exchange of the glycoprotein encoded by the ITGAM gene was reported in neonatal alloimmune neutropenia. An update of the current HNA nomenclature based on the new findings was provided in 2016 by the ISBT Granulocyte Immunobiology Working Party nomenclature subcommittee. Conclusions: The molecular basis of each of the five HNA antigen systems has been decoded during the past decades. This enables reliable molecular typing strategies, antibody detection and specification as well as development of new assays based on recombinant antigens. However, research on HNA alleles, antigens, and antibodies is not finally terminated and also in the future will add new findings.

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“…In contrast, immunogenicity of HNA-3b seems to be much lower [82], and also the clinical effect of HNA-3b alloantibodies is less severe. …”

Section: Hna-3mentioning

confidence: 99%

Section: Hna-3mentioning

confidence: 99%

Molecular Genetics of the Human Neutrophil Antigens

Flesch

Reil²

2018

Transfus Med Hemother

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“…1 Although the pathogenesis of TRALI is only partially resolved, an increasing number of studies have confirmed the role of antibodies against HLA and HNA antigens in the development of TRALI. [2][3][4][5][6] Recent case control studies have shown that HLA Class I antibodies are weak triggers of TRALI compared to HLA Class II and HNA antibodies, [7][8][9] and a smaller study even debated the involvement of HLA antibodies at all. 10 TRALI accounted for 47% of the transfusion-related fatalities reported to the US Food and Drug Administration from 2005 through 2010.…”

mentioning

confidence: 99%

Screening for HLA antibodies in plateletpheresis donors with a history of transfusion or pregnancy

Clippel¹,

Baeten²,

Torfs³

et al. 2014

Transfusion

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BACKGROUND: Transfusion-related acute lung injury (TRALI) is known as a life-threatening complication of transfusion. HLA and HNA antibodies have been associated with the immune pathway of TRALI. Since donors with a history of transfusion and/or pregnancy are presumed to have an increased risk of carrying such antibodies, we investigated the association of a history of transfusion or pregnancy with the occurrence of HLA alloimmunization in our donor population. STUDY DESIGN AND METHODS:A total of 1018 female plateletpheresis donors and male plateletpheresis donors with a history of transfusion were enrolled in the study. Included donors were systematically screened, using Luminex technology, for anti-HLA Class I and II. The association of donor history with HLA alloimmunization status was analyzed. RESULTS: The overall alloimmunization rate was 20.2%. In 0.0% of the nulliparous transfused female donors and in 1.3% of the transfused male donors, anti-HLA were detected. Thirty-one percent of the parous women versus 4.2% of the nulliparous women screened positive for anti-HLA. The rate of HLA alloimmunization increased with parity. CONCLUSION: Our data indicate that a history of transfusion is a minor risk factor for immunization against HLA antigens. In contrast, former pregnancies constitute a major risk factor for the development of HLA antibodies. Since HLA alloimmunization rate increases with parity, TRALI risk reduction measures should focus on this particular donor population. Repeated testing of female plateletpheresis donors after each pregnancy is implemented in our blood service.

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“…Genotyping methods recently were developed based on the molecular characterization of HNA-3 32,33 that could allow for screening of donors at risk of developing HNA-3a antibodies (eg, previously pregnant women). Reil et al recently developed such a method using polymerase chain reaction sequence-specific primers to genotype HNA-3a and HNA-3b of 398 blood donors.…”

Section: Hna Genotypingmentioning

confidence: 99%

Spotlight on pathogenesis of TRALI: HNA-3a (CTL2) antibodies

Storch

Hillyer

Shaz

2014

Blood

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Human neutrophil antigen-3a (HNA-3a) antibodies contained in donor plasma can result in severe, sometimes fatal transfusion-related acute lung injury (TRALI). Recent developments in TRALI secondary to antibodies to HNA-3a antigen span diagnosis, pathophysiology, treatment, and prevention resulting in improved understanding, potential treatments, and mitigation strategies. First, on the molecular level, characterization of HNA-3 antigen has allowed for genotyping methods that clarify population prevalence. Related work has led to generation of multiple antibody detection assays. These assays aid in determining potential populations at risk and potential mitigation strategies. Second, the development of TRALI requires a hit from the patient and from the product. Anti-HNA-3a is one of the product-derived factors and appears to result in TRALI by binding directly to pulmonary endothelium as well as to neutrophils expressing the corresponding antigen. Finally, potential mitigation strategies include red blood cell product filtration to remove anti-HNA-3a as well as other antibodies.

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Geno‐ and phenotyping and immunogenicity of HNA‐3

Abstract: The PCR-SSP method allows reliable determination of the HNA-3a and -3b genotypes; approximately 7% of HNA-3b homozygous women develop antibodies when exposed to the HNA-3a antigen during pregnancy.

Cited by 58 publications

References 21 publications

Molecular Genetics of the Human Neutrophil Antigens

Molecular Genetics of the Human Neutrophil Antigens

Screening for HLA antibodies in plateletpheresis donors with a history of transfusion or pregnancy

Spotlight on pathogenesis of TRALI: HNA-3a (CTL2) antibodies

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