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Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 1115-1116
CORRESPONDENCE
Neutrophil Antigen (Fc RIIIB) SH Gene Frequencies in Six Racial
Groups
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LETTER |
To the Editor:
Human leukocyte surface receptors specific for the Fc portion
of IgG play a critical role in immune function by coupling the humoral
and cellular immune systems. The Fc receptor III (FcRIII) (CD 16),
one of three Fc receptor classes, is encoded by two highly homologous
genes on chromosome 1.1 FcRIIIA encodes the transmembrane receptor expressed on macrophages and natural killer cells and is not
known to be polymorphic. FcRIIIB encodes the
glycosylphosphatidylinositol (GPI)-linked receptor expressed on
neutrophils and has three isoforms: NA1, NA2, and the recently
described SH.2 SH-positive individuals possess an
additional copy of the FcRIIIB gene, which may occur in tandem with
NA2-FcRIIIB.3 The nucleotide sequence of the NA1 and NA2
genes both predict a protein containing 233 amino acid residues;
however, the two alleles differ by five base substitutions (nts 141, 147, 227, 277, and 349) within exon 3, which predict amino acid changes
at positions 36, 65, 82, and 106 of the translated peptide.4 SH differs from NA2 by only one base substitution (nt 266, C  A); this substitution predicts an amino acid change (Ala Asp) at position 60.2
The NA antigens, which are difficult to identify by serologic tests
(ie, granulocyte immunofluorescence or agglutination), are clinically
important because they are the most frequent targets of neutrophil
antibodies in neonatal alloimmune neutropenia (NAN), transfusion-related acute lung injury, and chronic benign autoimmune neutropenia of infancy. An SH-positive frequency of 5% has been reported for Caucasians; however, its prevalence in other racial groups
is unknown.2,3 Because alloimmunization to SH has been
reported to cause NAN, its distribution in other racial groups is
important.2,5 Therefore, individuals (n = 799) of
African American, Asian Indian, Caucasian, Hispanic, Korean, and Native American descent were SH genotyped by allele-specific polymerase chain
reaction (AS-PCR; Fig 1) essentially as
described by Bux et al, and gene frequencies were established (Table
1).2
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| Fig 1.
SH typing by ASPCR. Twenty-five µL of each reaction was
electrophoretically analyzed on a 2% ethidium bromide stained agarose
gel. Lane 1, size standard; lane 2, negative control; lane 3, SH-positive sample; and lane 4, SH-negative sample.
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The highest SH gene frequency (22.5%) was observed in African
Americans, whereas SH was not observed in 101 Koreans. NA1 and NA2 gene
frequencies for African Americans, Asian Indians, Caucasians, Hispanics, Native Americans, and Asian populations have been reported by our laboratory and others.6,7 In general, NA2 is more common in African, Asian Indian, and Caucasian populations (gene frequencies of 70% to 63%, respectively) and becomes less
common as one examines populations endogenous to the Americas and Asia (gene frequencies of 55% to 30%, respectively).6,7 In
this study, the overall distribution of SH paralleled the NA2
frequency, being more common in Western populations than in Eastern
populations. All SH-positive individuals were also NA1/NA2 genotyped;
no SH-positive, NA1 homozygotes were observed. This is consistent with
the proposed tandem genomic localization of NA2 and SH.3
The high SH frequency in African Americans suggests that this group may
be at a higher risk for alloimmunization to this antigen.
Martin J. Hessner
Sachin M. Shivaram
David M. Dinauer
Brian R. Curtis
Debra J. Endean
Richard H. Aster
The Diagnostic Laboratories of The Blood Center
Milwaukee,
WI
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REFERENCES |
1.
Peltz GA, Grundy HO, Lebo RV, Yessl H, Barsh GS, Moore KW:
Human FcRIII: Cloning, expression, and identification of the chromosomal locus of two Fc receptors for IgG.
Proc Natl Acad Sci USA
86:1013, 1989[Abstract/Free Full Text]
2.
Bux J, Stein E-L, Bierling P, Fromont P, Clay M, Stroncek D, Santoso S:
Characterization of a new alloantigen (SH) on the human neutrophil Fcreceptor IIIb.
Blood
89:1027, 1997[Abstract/Free Full Text]
3.
Koene HR, Kleijer M, Roos D, de Haas M, Con dem Borne AEG:
FcRIIIB gene duplication: Evidence for presence and expression of three distinct FcRIIIB genes in NA(1+,2+)SH(+) individuals.
Blood
91:673, 1998[Abstract/Free Full Text]
4.
Ory PA, Clark MR, Kwoh EE, Clarkson SB, Goldstein IM:
Sequences of complementary DNAs that encode the NA1 and NA2 forms of Fc receptors III on human neutrophils.
J Clin Invest
84:1688, 1989
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Curtis BR, Ebert DD, Hessner MJ, Aster RH:
Neonatal alloimmune neutropenia due to anti-SH.5th European Symposium on Platelet and Granulocyte Immunobiology, S'Agaró, Girona, Spain, May 9-12, 1998, p 52 (abstr)
6.
Hessner MJ, Curtis BR, Endean DJ, Aster RH:
Determination of neutrophil antigen NA gene frequencies in five different ethnic groups by the polymerase chain reaction with sequence-specific primers (PCR-SSP).
Transfusion
36:895, 1996[Medline]
[Order article via Infotrieve]
7.
Lin M, Chen CC, Wang CL, Lee HL:
Frequencies of neutrophil-specific antigens among Chinese in Taiwan.
Vox Sang
66:247, 1994[Medline]
[Order article via Infotrieve] (letter)
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