IMMUNOHEMATOLOGY

The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency

Corresponding Author

Jianming Wu

[email protected]

Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, Minnesota

Address reprint requests to: Jianming Wu, PhD, Department of Veterinary and Biomedical Sciences, University of Minnesota, 235B AnSc/VetMed Building, 1988 Fitch Avenue, St Paul, MN 55108; e-mail: [email protected]; or Bayat Behnaz, PhD, Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany; e-mail: [email protected].Search for more papers by this author

Yunfang Li,

Yunfang Li

Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, Minnesota

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Randy M. Schuller,

Randy M. Schuller

North Central Blood Services, National Neutrophil Reference Laboratory, American Red Cross, St Paul, Minnesota

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Ling Li,

Ling Li

Department of Clinical and Experimental Pharmacology, University of Minnesota Twin Cities, Minneapolis, Minnesota

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Anne-Sophie Litmeyer,

Anne-Sophie Litmeyer

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

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Gregor Bein,

Gregor Bein

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

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Ulrich J Sachs,

Ulrich J Sachs

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

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Behnaz Bayat,

Corresponding Author

Behnaz Bayat

[email protected]

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

Jianming Wu,

Corresponding Author

Jianming Wu

[email protected]

Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, Minnesota

Yunfang Li,

Yunfang Li

Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, Minnesota

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Randy M. Schuller,

Randy M. Schuller

North Central Blood Services, National Neutrophil Reference Laboratory, American Red Cross, St Paul, Minnesota

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Ling Li,

Ling Li

Department of Clinical and Experimental Pharmacology, University of Minnesota Twin Cities, Minneapolis, Minnesota

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Anne-Sophie Litmeyer,

Anne-Sophie Litmeyer

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

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Gregor Bein,

Gregor Bein

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

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Ulrich J Sachs,

Ulrich J Sachs

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

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Behnaz Bayat,

Corresponding Author

Behnaz Bayat

[email protected]

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

First published: 03 March 2019

https://doi.org/10.1111/trf.15222

Citations: 17

JW and BB contributed equally to the study.

This study was supported by the National Institute of HEALTH grant R21AI125729 and a Faculty Research Development grant (FRD #14.20) from the University of Minnesota Academic Health Center.

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Abstract

BACKGROUND

Human neutrophil antigen-2 (HNA-2) is exclusively expressed on neutrophils. HNA-2–deficient individuals (HNA-2 null) are susceptible to produce isoantibodies. The nonsense CD177 coding single-nucleotide polymorphism (SNP) c.787A>T has been demonstrated as the primary genetic mechanism for HNA-2 deficiency. We hypothesized that the other genetic variants also contribute to HNA-2 expression variation and deficiency.

STUDY DESIGN AND METHODS

The deficiency, density, and percentage of HNA-2 antigen on neutrophils from 292 healthy blood donors were determined in flow cytometry. CD177 genotypes were determined by genomic DNA sequence analyses. The full-length CD177 cDNAs were amplified and sequenced. Additionally, the whole CD177 genomic sequence in eight HNA-2–null immunized women and four HNA-2–positive donors were analyzed with next-generation sequencing. The associations of CD177 SNP genotypes with HNA-2 expression variation were statistically analyzed.

RESULTS

A functional CD177 SNP c.1291G>A was identified in the current study. Atypical (trimodal) HNA-2 expression phenotype was consistently observed in donors carrying the heterozygous c.1291G/A genotype. Phenotype-genotype analyses of SNP c.787A>T and SNP c.1291G>A revealed that all homozygous 787T-1291G (TG/TG) genotype donors were HNA-2 null in healthy blood donors. On the other hand, five of eight HNA-2–immunized females were homozygous for the 787T-1291G (TG/TG) genotype while the other three HNA-2–immunized females had the 787T-1291G/787A-1291A (TG/AA) genotype and the lowest HNA-2 expression was observed in healthy subjects with the 787T-1291G/787A-1291A (TG/AA) and 787A-1291A/787A-1291A (AA/AA) genotype.

CONCLUSION

The CD177 SNP c.1291G>A is a genetic determinant for the atypical and low HNA-2 expression, which also contributes to HNA-2 deficiency phenotype.

CONFLICT OF INTEREST

The authors have disclosed no conflicts of interest.

REFERENCES

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Volume59, Issue5

May 2019

Pages 1836-1842

The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency

Abstract

BACKGROUND

STUDY DESIGN AND METHODS

RESULTS

CONCLUSION

CONFLICT OF INTEREST

REFERENCES

Citing Literature

References

Information

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The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency

Abstract

BACKGROUND

STUDY DESIGN AND METHODS

RESULTS

CONCLUSION

CONFLICT OF INTEREST

REFERENCES

Citing Literature

References

Related

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