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2356 Part XIII: Transfusion Medicine Chapter 137: Human Leukocyte and Platelet Antigens 2357

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TABLE 137–2. Human Neutrophil Antigens gene. 41,42 FCGR3B 03 encodes both HNA-1b and HNA-1c. FCGR3B 02
also encodes HNA-1d which is characterized by the FcγRIIIb sequence
Location of Ala78–Asn82. 43
System Alleles Antigens Genes The antigen frequencies of three of the alleles vary widely among
HNA-1 HNA-1a, -1b, FcγRIIIb FCGR3B*01, different racial groups. Among whites, HNA-1b is the most common
-1c, and 1d FCGR3B*02, and antigen (Table 137–3), 44–46,48–50 but in Japanese and Chinese populations
FCGR3B*03 HNA-1a is most common. 44,46,48,49,51 The frequency of the gene encoding
HNA-2 HNA-2 NB1gp CD177 HNA-1c antigen also varies among racial groups. HNA-1c is expressed
by neutrophils in 4 to 5 percent of whites, 25 to 38 percent of African
HNA-3 HNA-3a Choline SLC44A2*01 Americans, and 10 percent of Brazilians. 52,53 The antigen frequency of
transporter-like
protein-2 (CTL2) HNA-1d should be nearly the same as that of HNA-1b, but it has not yet
been investigated.
HNA-4 HNA-4a α integrin, ITGAM*01 Several other sequence variations in FCGR3B have been
M
C3bi-receptor described. Most of these chimeric alleles have single-base substitutions
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(CR3)(CD11b)
involving one of the five single nucleotide polymorphisms (SNPs) that
HNA-5 HNA-5a αL integrin, ITGAL*01 distinguish FCGR3B 1 and FCGR3B 2. FCGR3B alleles that most closely
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LFA-1(CD11a) resembled FCGR3B 2 were found more often in African Americans than
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in whites or Japanese. 46,47
Genetic deficiencies of neutrophil FcγRIIIb and HNA-1 antigens
Molecular Biology have also been reported. Among whites the incidence of individuals
FcγRIIIb and the HNA-1 antigens are encoded by the FCGR3B gene homozygous for FCGR3B deletion is approximately 0.1 percent. 52,54,55
located on chromosome 1q23–24. FCGR3B is highly homologous to However, among Africans and African Americans the incidence is
FCGR3A, which encodes FcγRIIIa. In addition to the polymorphic much higher. In one study, 3 of 126 Africans were found to be FCGR3B
FCGRB3B nucleotides only four others differ between FCGR3B and deficient, and in another study, 1 of 53 were found to be FCGR3B
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FCGR3A. The most important difference between the two genes is a deficient. 46
C-to-T change at 733 in FCGR3B that creates a stop codon. As a result,
FCGR3A has 21 more amino acids than FCGR3B and FCGR3B is a Function of HNA-1 Antigens
glycosylphosphatidylinositol (GPI)-anchored rather than a transmem- Polymorphisms in FcγRIIIb have some effect on neutrophil function.
brane glycoprotein (GP). Neutrophils that are homozygous for HNA-1b have a lower affinity
The four HNA-1 system antigens are encoded by three alleles. The for immunoglobulin (Ig) G than those homozygous for HNA-1a.
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FCGR3B 01 allele differs from FCGR3B 02 by only five nucleotides in Neutrophils from those who are homozygous for HNA-1b phagocy-
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the coding region, at positions 141, 147, 227, 277, and 349. 35–38 Four tize erythrocytes sensitized with IgG and IgG anti-Rh monoclonal
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of the nucleotide changes result in changes in amino acid sequence antibodies and bacteria opsonized with IgG at a lower level than neu-
between the HNA-1a and HNA-1b forms of FcγRIIIb. The glycosyla- trophils homozygous for HNA-1a. 57,58 1
tion pattern of FcγRIIIb differs between the two antigens because of two
nucleotide changes at bases 227 and 277. The HNA-1b form of FcγRIIIb
has six N-linked glycosylation sites and the HNA-1a form has four gly- THE HNA-2 ANTIGEN SYSTEM
cosylation sites. The HNA-2 Antigen
The FCGR3B 03 allele is identical to FCGR3B 02 except for a HNA-2 is an isoantigen without allelic variation. HNA-2 is expressed
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C-to-A substitution at nucleotide 266 resulting in an alanine to aspar- only on neutrophils, neutrophilic metamyelocytes, and myelocytes. 39,59
tate change at amino acid 78 of FcγRIIIb. In many cases, FCGR3B 03 It’s unique in that it is expressed on subpopulations of neutrophils. The
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exists on the same chromosome with a second or duplicate FCGR3B mean size of the HNA-2-positive subpopulation of neutrophils is 45 to
TABLE 137–3. Human Neutrophil Antigen Frequencies
Antigen Frequencies
Europeans/ Africans and African Brazilians/
System Alleles North Americans Americans Asians Argentineans
HNA-1 HNA-1a 58% 59–67% 91% 68%
HNA-1b 88% 71–88% 54% 76%
HNA-1c 5% 25–38% <1% 5–10%
HNA-1d NA NA NA NA
HNA-2 HNA-2 95–97% 95% 89–99% NA
HNA-3 HNA-3a 89–92% NA NA NA
HNA-4 HNA-4a 99% NA 99% 97%
HNA-5 HNA-5a 85% 88% 81–96% 78–92%

NA, not available.

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