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Review

Blood Groups in Infection and Host Susceptibility

Laura Cooling
Laura Cooling
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
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  • For correspondence: lcooling@med.umich.edu
DOI: 10.1128/CMR.00109-14
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  • Figure1
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  • FIG 1
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    FIG 1

    Synthesis of H, A, and B antigens. The H antigen is formed by the addition of an α1-2 fucose (blue diamonds) by FUT1 or H-glycosyltransferase. H antigen can then serve as a substrate for ABO glycosyltransferase. Group A individuals express an α1-3 N-acetylgalactosamine (GalNAc) (red trapezoid), and group B individuals express an α1-3 galactose (Gal) (orange circles). Group O individuals have inactive ABO genes and express only the H-antigen precursor. The Bombay phenotype (Oh) lacks H, A, and B antigens due to null FUT1 alleles.

  • FIG 2
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    FIG 2

    Relationship and synthesis of type 1 (Lea and Leb) and type 2 (LeX and LeY) antigens by Lewis (FUT3) and Secretor (FUT2) enzymes and their modification by ABO.

  • FIG 3
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    FIG 3

    ABO gene and major A, B, and O alleles. The ABO gene resides on chromosome 9q34.1 and contains 7 exons, which encode a 354-aa glycoprotein. The glycoproteins encoded by the A (ABO*A1) and B (ABO*B) consensus alleles differ by 4 aa, 3 of which are functionally important (aa 235, 266, and 268). Group O alleles belonging to the O 1 family contain a deletion in exon 6, leading to a frameshift and a premature stop codon. Alleles belonging to the O 2 family share a mutation at aa 268. Shown in red are the SNP designations commonly used in genomic studies for ABO typing.

  • FIG 4
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    FIG 4

    Cholera lectin binding sites. Ganglioside GM1 is the primary CTx receptor. The binding site involves residues on adjacent B subunits. A second, weaker binding site for LeY-type epitopes is located along the other face of the B subunit (yellow diamonds).

  • FIG 5
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    FIG 5

    Synthesis of globo- and related neolacto- and gala-series GSLs. Also shown are agents capable of inhibiting GSL synthesis (PPMP), inducing enzyme expression (TNF and H. pylori), and inactivating mutations (Pk and p phenotypes). Microbial lectins recognizing GSL antigens are included.

  • FIG 6
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    FIG 6

    Globoside and parvovirus B19. (A) Distribution of Gb4 in human tissues (mean percent total neutral GSLs ± standard deviation). HUVEC, human umbilical vein endothelial cell. (B) The parvovirus B19 capsid is composed of VP2 (light blue) and VP1 (dark blue) protomers. B19 binds to Gb4 on cell membranes (for example, red cells), inducing a conformational change in VP1 with surface expression of the VP1u peptide. The majority of the modified B19 dissociates, where it may adhere to a high-affinity coreceptor on erythroblast membranes. It is likely that the receptor lies within a Gb4-enriched microdomain that facilitates B19 uptake.

  • FIG 7
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    FIG 7

    Duffy or DARC antigen and gene. (A) The DARC glycoprotein contains a large extracellular domain and 7 transmembrane domains. The amino-terminal extracellular domain contains the P. vivax PvDBP binding site (aa 8 to 42), of which the negatively charged Fy6 epitope (aa 19 to 26) is critical. The Fya/b polymorphism resides at amino acid 42. A missense mutation in the first cytoplasmic loop of the transmembrane domain (Arg89Cys) is responsible for the FyX phenotype, which is associated with weak DARC expression. (B) The DARC gene resides on chromosome 1q23.2. DARC expression on red cells is silenced in the FY*B ES allele, which contains a mutation in a GATA promoter site. The SNP designations and the location of FY*B ES, FY*B/FY*A, and FY*X are shown.

  • FIG 8
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    FIG 8

    Diego blood group (AE1; band 3; SLC4A1). AE1 exists as dimers and tetramers and is preferentially located at junctional complexes and the “band 3-ankyrin” metabolon (shown). The amino-terminal cytoplasmic domain is involved in oligomerization and interacts with the underlying cytoskeleton. Several glycolytic enzymes and hemoglobin derivatives or hemichromes (methemoglobin and denatured hemoglobin) associate with the amino-terminal domain. Carbonic anhydrase is associated with the cytoplasmic carboxy tail. The large transmembrane domain is an anion transporter, exchanging Cl−/HCO3 − anions. Several high/low-incidence antigens are located along the extracellular loops. The high-incidence Wrb antigen requires interaction with glycophorin A for expression. A 27-bp deletion at the junction of the amino-terminal and transmembrane domain is responsible for Southeast Asian ovalocytosis (SLC4A1Δ27) (in red). AE1 contains a single massive N-glycan that expresses ABO and is responsible for 50% of all the ABO antigens on red blood cells.

  • FIG 9
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    FIG 9

    MNSs blood group (GYPA and GYPB). Glycophorins A, B, and E are located together on chromosome 4q28-q31 and can undergo recombination, leading to hybrid glycophorins (for example, Henshaw, GP.Mur, and GP.Dantu) and null phenotypes [En(a−), U−, and Mk]. The MN antigens are defined by the first 5 amino acids and O-linked glycans on glycophorin A. Glycophorin A contains 15 O-glycan sites and >20 high/low antigens. Glycophorin A is physically associated with AE1/band 3 and participates in Wrb antigen expression located on AE1. The location of 3 high/low polymorphisms showing evidence of selection (16) and the trypsin cleavage site are shown. The S/s antigens are a single polymorphism on glycophorin B. The U antigen is located along a short peptide segment near the membrane.

  • FIG 10
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    FIG 10

    Gerbich blood group (GYPC and GYPD). Glycophorins C and D are products of the GYPC gene and differ by 21 amino acids at the amino-terminal end. Both proteins interact with the cytoskeleton elements at junctional complexes. GYPC contains a single N-glycan that binds the P. falciparum protein EBA140/BAEBL. The Gerbich phenotype is a deletion mutant lacking exon 3. The altered protein is underglycosylated and expresses an immature, high-mannose N-glycan. In addition, there is an altered interaction with the junctional complexes, leading to ovalocytosis.

  • FIG 11
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    FIG 11

    Knops blood group (CR1; CD35). The CR1 variant on red cells is composed of 30 complement consensus repeats arranged as 4 long homologous repeats (LHR-A to -D). CCPs involved in complement binding are highlighted (purple) and referred to as sites 1, 2, and 2′. These sites also serve as binding sites for malarial proteins (PfRh4 and PfEMP). LHR-D may interact with mannose binding lectin. The Knops antigens are located in CCP25 and CCP26 (blue). The sites of two mutations associated with weak CR1/Knops expression are highlighted in green. Also shown is the trypsin cleavage site on CR1.

  • FIG 12
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    FIG 12

    OK blood group (Basigin; CD147). CD147 is a member of the immunoglobulin superfamily. The most common isoform contains single C-type and V-type domains. The Ok(a+/a−) polymorphism is located at amino acid 92. Several amino acids that are believed to participate in PfRh5 binding are highlighted (612, 615). CD147 is also able to bind cyclophilins (A and B) and plays a role in many viral infections (HIV, measles virus, and SARS-CoV).

  • FIG 13
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    FIG 13

    Cromer blood group. Decay-accelerating factor (DAF) (CD55) is a GPI-linked glycoprotein composed of 4 complement consensus domains (CCPs), a heavily glycosylated stalk region, and a GPI tail. The location of Cromer antigens is shown on the right. C3 convertase binding is located along CCP2-CCP3. CCP domains involved in binding specific echoviruses (EV), enteroviruses (ENV), bacteria, and MAbs are shown. H. pylori and many enteroviruses appear to require the entire molecule for binding. Like most GPI-linked glycoproteins, DAF is a raft protein and is localized at or recruited into glycolipid-enriched microdomains (GEMs).

  • FIG 14
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    FIG 14

    CD44/Indian blood group. CD44s is a 341-aa glycoprotein that possesses a globular link domain with three disulfide bonds (hatched lines) and 5 to 6 N-glycans. The globular domain is capable of binding hyaluronic acid (HA), including hyaluronic acid on S. pyogenes. Peptide regions critical for HA binding are highlighted in red. The glycosylated stem region expresses both O-linked glycans (purple) and chondroitin sulfate (blue hexagons) and can vary between tissues due to alternate splicing and glycosylation. The AnWj epitope is hypothesized to lie in the stalk region and is a receptor for H. influenzae. The molecule contains a long cytoplasmic domain that interacts with ankyrin and ERM proteins to modulate the cytoskeleton. Binding by L. monocytogenes invokes ezrin binding and phosphorylation with actin polymerization.

  • FIG 15
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    FIG 15

    Raph blood group (CD151; MER2). Raph is located on the tetraspanin CD151. Like all tetraspanins, CD151 is a multipass protein with two extracellular loops. The EC2 domain is functionally critical for protein function. Tetraspanins can act as receptors for viruses or may help organize receptors within tetraspanin-enriched membrane domains.

Tables

  • Figures
  • TABLE 1

    Human blood group systemsc

    CDaBlood group system Gene Protein function(s)No. of molecules per RBCd
    Group no.NameSymbolNo. of AgsbChromosomeDesignation(s)
    —e 001ABOABO49q34.2 ABO Glycosyltransferase0–1 million
    CD235002MNSMNS464q31.21 GYPA Red cell zeta potentialGYPA, 1 million; GYPB, 250,000
    GYPB Band 3-ankyrin complex
    Junctional complex
    CD77003P1PKP1PK422q13.2 A4GALT1 α1,4-Galactosyltransferase
    CD240004RhRh521p36.11 RHD Ammonium transport100,00–200,000 trimers
    RHCE Band 3 metabolon
    CD239005LutheranLutheran2019q13.32 LU Laminin receptor, erythroid maturation1,500–4,000
    CD238006KellKEL347q34 KEL Endothelin-3-converting enzyme3,500–18,000
    —007LewisLE619p13.3 FUT3 α3/4-FucosyltransferaseAdsorbed from plasma
    CD234008DuffyFY51q23.2 DARC Chemokine receptor6,000–13,000
    —009KiddJK318q12.3 SLC14A1 Urea transport14,000
    CD233010DiegoDI2217q21.31 SLC4A1 Band 3/AE1/anion exchange, membrane-cytoskeleton stability, band 3 metabolon-gas exchange, RBC senescence1 million dimers, tetramers
    —011CartwrightYT27q22.1 ACHE Acetylcholinesterase7,000–10,000
    CD99012XgXG2Xp22.33 XG, MIC2 Adhesion molecule200–2,000
    —013SciannaSC71p34.2 ERMAP Unknown, adhesion?Unknown
    CD297014DombrockDO812p12.3 ART4 ADP-ribosyltransferaseUnknown, likely raft associated
    —015ColtonCO47p14.3 AQP1 Water transport, band 3 metabolon120,000–160,000 tetramers
    CD242016Landsteiner-WienerLW319p13.2 ICAM4 Adhesion molecule2,800–4,400
    —017Chido/RodgersCH/RG96p21.3 C4A, C4B Complement C4Adsorbed from plasma
    CD173018HH119q13.33 FUT1 α1,2-Fucosyltransferase, type 2 H antigen
    (SEf)H119q13.33 FUT2 α1,2-Fucosyltransferase, type 1, 3, and 4 H antigens, secretor (ABH, Leb)
    —019KxKX1Xp21.1 XK Unknown1,000
    CD236020GerbichGE112q14.3 GYPC Glycophorins C and D, junctional complex protein, lateral membrane stabilityGYPC, 135,000; GYPD, 50,000
    CD55021CromerCROM161q32.2 CD55 DAF, complement regulation20,000, raft associated
    CD35022KnopsKN91q32.2 CR1 Complement receptor 1, complement regulation20–1,500
    CD44023IndianIN411p13 CD44 Cell adhesion2,000–5,000
    CD147024OkOK319p13.3 BSG Basigin, RBC trafficking and senescence, cytophilin receptor, cell adhesion and signaling3,000
    CD151025RaphRAPH111p15.5 CD151 Tetraspanin, cell adhesionUnknown, likely raft associated
    CD108026John Milton HagenJMH615q24.1 SEMA7A T-cell-mediated inflammation, integrin receptor (α1β1)Unknown, likely raft associated
    —027II16p24.2 GCNT2 β1,6-N-Acetylglucosaminyltransferase
    —028GlobosideGLOB23q26.1 B3GALNT1 β1,3-N-Acetylgalactosaminyltransferase>10% RBC lipids, 70% RBC GSLs
    —029GillGIL19p13.3 AQP3 Aquaglyceroporin; water, glycerol, peroxide transport25,000
    CD241030Rh-associated glycoproteinRHAG46p21-qter RHAG Ammonium transport, associated RhD and RhCE100,000–200,000 trimers
    —031ForssmanFORS19q34.13 GBGT1 α1,3-N-AcetylgalactosaminyltransferaseRare expression
    CD338032JrJR14q22 ABCG2 ATP-dependent transport, multidrug resistance, folate homeostasisUnknown
    —033LanLAN12q36 ABCG6 Porphyrin/heme transportUnknown
    —034VelVEL11p36.32 SMIM1 Regulation of red cell formationUnknown
    • ↵a CD, cluster designation.

    • ↵b Number of RBC antigens recognized by the ISBT.

    • ↵c See references 1 and 2.

    • ↵d No. of blood group-active proteins or glycans per red cell.

    • ↵e —, no CD designation.

    • ↵f SE, Secretor. Secretor is related to H but has no official ISBT designation.

  • TABLE 2

    Distribution of blood types in different populations

    Blood group systemBlood group phenotypePopulation distribution (%) by countrycReferences
    United States AfricaaBrazilChinaIndia
    WhitesBlacks
    ABOA4027194122–2922 2, 6 – 8, 29, 713
    B11201492633
    AB44<136–137
    O454967472837
    LewisLe(a+b−)2723148021 2, 9 – 12, 29
    Le(a−b+)725554677161
    Le(a+b+)000020b 0
    Le(a−b−)6221425918
    PP1 7994NANA25–2972 2, 7, 9, 12, 13, 29
    P2 216NANA69–7528
    MNSsM+ N− 282537253134.6 2, 7, 8, 12, 14 – 20, 29
    M+ N+ 504936515054.1
    M− N+ 222627241911.3
    S+ s− 117276<111.3
    S+ s+ 44244039643.9
    S− s+ 456955559444.7
    Henshaw036–27000
    Mi.III<0.1<0.1NANA6NA
    DiegoDi(a+)0.010.010.012–544–10NA 2, 9, 21 – 23, 29
    DuffyFy(a+b−)1793339342.1 2, 8, 12, 14, 15, 17, 24, 29
    Fy(a+b+)491<12774.5
    Fy(a−b+)3422835<112.3
    Fy(a−b−)06889–100500.3
    KnopsKna 98991009810098 25 – 27
    Knb 4<1NA202
    McCa 989089–929310078
    McCb 14449–5442022
    Sl19951–6130–387010048
    Sl2<1809586052
    KCAM98NA205357–82NA
    • ↵a Values are for West or Central Africa.

    • ↵b High incidence of Le(a+b+) in other Asian Pacific populations (for example, Japan).

    • ↵NA, not available.

  • TABLE 3

    ABO typing of red cells and plasma/serum

    ABO typeGeneaRBC groupingb (forward or antigen type) Serum groupingc (back type)
    FUT1ABOAnti-AAnti-BUEA-1bA1 RBCB RBCO RBC
    A1 ++++000+0
    A2 d +++0++/0+0
    B++0++0+00
    Oe +000++++0
    Oh f (Bombay)0 (hh)+000+++
    • ↵a Inheritance of at least one functional H gene (FUT1) and ABO gene.

    • ↵b Testing for ABO antigens on red cells with monoclonal anti-A and anti-B. H antigen is detected with the Ulex europaeus lectin (UEA-1).

    • ↵c Testing of plasma/serum against red cells of a known ABO type to detect anti-A, anti-B, or anti-H.

    • ↵d A2 is the most common weak A phenotype, is characterized by increased H antigen levels, and may possess anti-A1. A2 and other weak A red cells do not agglutinate with the anti-A lectin of Dolichos biflorus.

    • ↵e Group O is due to the homozygous inheritance of ABO amorph alleles.

    • ↵f Bombay Oh is a rare autosomal-recessive phenotype due to amorph FUT1 (hh) and FUT2/Secretor (se/se). Bombay individuals lack H, A, and B antigens and possess hemolytic anti-A, anti-B, and anti-H.

  • TABLE 4

    Examples of A-active antigens, expression, and synthesis

    AntigenStructureaRBC type or other cell typebFucosyltransferase
    A1A2/AwkFUT1FUT2FUT3
    Type 1 A (A-1)GalNAcα1→3Galβ1→3GlcNAc→Rc +↓−+−
    ↑2
    Fucα1
    Type 1, ALeb GalNAcα1→3Galβ1→3GlcNAc→R+↓/0−++
    ↑2 ↑4
    Fucα1 Fucα1
    Type 2 A (A-2)GalNAcα1→3Galβ1→4GlcNAc→R+↓+−−
    ↑2
    Fucα1
    Type 2, ALeY GalNAcα1→3Galβ1→4GlcNAc→R+↓+−+
    ↑2 ↑3
    Fucα1 Fucα1
    Type 3 A (A-3)d (mucinous A)GalNAcα1→3Galβ1→3GalNAcβ1→3Galβ1→R+0++−
    ↑2 ↑2
    Fucα1 Fucα1
    Type 4 A (A-4)e (globo-A)GalNAcα1→3Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glc→Cer+0++−
    ↑2
    Fucα1
    Ganglio-Ae GalNAcα1→3Galβ1→3GalNAcβ1→4Galβ1→4Galβ1→4Glc→CerPig red cells, intestine +/−+−
    ↑2
    Fucα1
    O-glycanf A, H activeFucα1→2Galβ1→3GalNAc-O-Ser/ThrGastric mucosa (ALeb) −+−
    ↑6
    GalNAc1→3Gal1→3GlcNAcβ1
    ↑2
    Fucα1
    • ↵a Abbreviations: Cer, ceramide; Fuc, fucose; Gal, galactose; GalNAc, N-acetylgalactosamine; Glc, glucose; GlcNAc, N-acetylglucosamine.

    • ↵b Relative expression on A1 versus A2 and other Aweak subtypes.

    • ↵c R, upstream sequence of various sizes, which may be expressed on the glycoprotein or glycosphingolipid.

    • ↵d Found on A1 cells only and composed of repeating terminal A motifs, also known as repetitive A motifs.

    • ↵e Found as glycosphingolipids only.

    • ↵f Core 2 O-glycan with A and H activity found on gastric mucosa (15% of total ALeb individuals).

  • TABLE 5

    Relationship between Lewis and Secretor genotypes and phenotypes

    Lewis phenotypeGeneaSecretor typebSecreted antigenc
    FUT2FUT3LeaLebABO
    Lewis positive
        Le(a+b−)0+N+00
        Le(a−b+)++Y+++
        Le(a+b+w)d + (Sew )+Y+↓↓
    Lewis null
        Le(a−b−)+0Y00+
        Le(a−b−)00N000
    • ↵a Inheritance of at least one functional glycosyltransferase gene.

    • ↵b Ability to secrete ABH antigens in saliva and other secretions. N, nonsecretor; Y, secretor.

    • ↵c Presence of Lewis and type 1 ABH antigens in saliva and other secretions.

    • ↵d Very weak Leb expression due to inheritance of an SeW FUT2 allele. Le(a+b+) may reflect either the SeW /SeW or SeW /se genotype. SeW /se can also be typed as Lewis null.

  • TABLE 6

    Comparison of blood group binding by CTx and hLT variants

    Toxin↑ disease severity group OB-subunit amino acid participating in blood group antigen recognitiona,b at position: Toxin bindinga
    37161845464748899294LeYBLeY
    Classical serotype O1 OgawaNQDQHGA T FNTR++
    Classical serotype O1 InabaNQDQHGA T FNTH++
    Classical serotype O139 (Bengal)YQDQYGAIFNTH+−
    El Tor serotype O1 InabaYQDQYGAIFNTH+−
    El Tor serotype O1 Inaba (I47→T)NAc QDQYGA T FNTH++
    ETEC hLTNQEQYGA T FNTN++
    • ↵a Data were extrapolated from references 117 and 119.

    • ↵b Thr47 associated with BLeY binding is highlighted in boldface type.

    • ↵c The mutant was not tested clinically but is hypothesized to lack ABO specificity relative to disease severity (119).

  • TABLE 7

    Globo-, gala-, and related neolacto-GSLsa

    GSLAlias(es)GSL structureGSL bindingb
    Stx1/2SEBS. suisPA-ILPapGParvovirus B19HIV
    Gala-GSL
        GalCerCerebrosideGal-Cer +
        SO4-GalCerSulfatideSO4-Gal-Cer +
        Gal2CerGalabiosyl-CerGalα1-4Gal-Cer++++ +
    LacCerCDHGalβ1-4Glc-Cer +
    GM3 NeuAcα2-3Galβ1-4Glc-Cer +
    Globo-GSL
        Gb3Pk, CD77 Galα1-4Galβ1-4Glc-Cer++ ++++ +
        Gb4P, globosideGalNAcβ1-3Galα1-4Galβ1-4Glc-Cerw+ + +++
        Gal-Gb4NOR1Galα1-4GalNAcβ1-3Galα1-4Galβ1-4Glc-Cer? +
        ForssmanForssmanGalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-Cer ++
        Gb5SSEA-3Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-Cer ++
        Fuc-Gb5Globo-HFucα1-2Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-Cer +
        MSGGLKE, SSEA-4NeuAcα2-3Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-Cer +++
        Gal-Gb5Band 0.03Galα1-4Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-Cer+ +
    Neolacto-GSL
        Lc3 GlcNAcβ1-3Galβ1-4Glc-Cer
        nLc4ParaglobosideGalβ1-4GlcNAcβ1-3Galβ1-4Glc-Cer
        αGal-nLc4P1Galα1-4Galβ1-4GlcNAcβ1-3Galβ1-4Glc-Cer+ +++
        GalNc-nLc4PX2GalNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-Cer
        NeuAc-nLc4SPGNeuAcα2-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-Cer
    • ↵a Abbreviations: Cer, ceramide; Fuc, fucose; Gal, galactose; GalNAc, N-acetylgalactosamine; Glc, glucose; GlcNAc, N-acetylglucosamine; NeuAc, N-acetylneuraminic acid; SSEA, stage-specific embryonic antigen; SPG, sialylparagloboside. The underlining represents the critical Galα1-4Gal linkage that is shared by all globo-GSLs.

    • ↵b + indicates recognition and binding to specific GSLs. Strong binding is indicated by ++. w+ indicates weak binding, and ? indicates unknown/not tested.

  • TABLE 8

    P blood group phenotypes

    TypeIncidence (%)Glycosyltransferase geneaGSL expressed on RBCcAntibody
    A4GALT1B3GALNT1GBGT1CDHGb3Gb4Gb5MSGGP1Other
    P1 80b ++0+++++tr++
    P2 20b ++0+++++tr+0 Anti-P1
    LKE-S80–90b , d ++0+++++tr++/0
    LKE-W10–20b , d ++0+++++tr↓+/0
    LKE-N1–2b , d ++0+++++trtr+/0 Anti-LKE (raree)
    P1 k Rare+00+++++000+ Anti-P
    P2 k Rare+00+++++0000 Anti-P
    pRare0+0+++00000PX2Anti-PP1Pk (Tja)
    NORRare++0+++++NANA+/0NOR
    Apae Rare++++++++NANA+/0Fors
    • ↵a Inheritance of at least one functional glycosyltransferase gene (+).

    • ↵b Incidence in the U.S. white population. See Table 1 for distributions in other populations.

    • ↵c Relative GSL expression on red cells. See Table 7 and Fig. 5 for structures and biosynthetic relationships. ↓, decreased; tr, trace.

    • ↵d LKE frequencies as summarized by Cooling and Kelly (360). Note that LKE is independent of P1 expression. The LKE type can occur on either the P1 or P2 background.

    • ↵e See reference 363.

  • TABLE 9

    Relationship between DARC genotype, phenotype, and P. vivax infectionf

    DARC genotypeaRed cell phenotypeDosage of DARCbPvDBP bindingcClinical infectiond
    Relative risk95% CI
    FY*A/FY*BES Fy(a+b−)+∼2.0 × 104 0.2040.09–0.87
    FY*A/FY*A Fy(a+b−)++∼4.5 × 104 0.7150.31–1.21
    FY*A/FY*X Fy(a+bw)e +NDND
    Fy(a+b−)e
    FY*A/FY*B Fy(a+b+)++∼5.8 × 104 1.00
    FY*B/FY*B Fy(a−b+)++∼7.2 × 104 2.701.36–5.79
    FY*B/FY*X Fy(a−b+)+NDND
    FY*B/FY*BES Fy(a−b+)+ND2.170.91–4.77
    FY*X/FY*BES Fy(a−bw)e wNDNDResistant to blood-stage infection (?)
    Fy(a−b−)e
    FY*BES /FY*BES Fy null00 Resistant to blood-stage infection
    • ↵a FY*A, DARC allele carrying the Fya antigen; FY*B, allele carrying the Fyb antigen; FY*X, allele encoding weak Fyb expression on all tissues; FY*BES , Fy-null allele carrying a GATA promoter mutation leading to a loss of DARC expression on red cells only (ES, erythroid silent).

    • ↵b Relative dose of DARC glycoprotein (+, 1 copy; ++, 2 copies; w, very weak [5% of normal]) on red cells based on genotype.

    • ↵c Binding of recombinant PvDBPII to human red cells (mean fluorescence intensity × percent positive red cells) by DARC genotype. Data are estimates based on graphed data reported by King et al. (515).

    • ↵d Relative risk of clinical P. vivax infection in the Brazilian Amazon by DARC genotype (515).

    • ↵e FY*X red cells can be serologically typed as Fy(b−) or Fy(bw) due to very weak Fyb expression (5% of normal).

    • ↵ND, not done.

  • TABLE 10

    Effect of O-linked glycans on P. falciparum RBC invasion

    Antigen(s)O-linked glycan structureSusceptibility to P. falciparumaDescription
    M/NEBA-175 receptorSensitive>70% O-glycan on GYPA, GYPB
    NeuAcα2→3Galβ1→3GalNAc-O-Ser/Thr Epitope anti-Pr
    ↑6
    NeuAcα2
    Can, Tm, M1, SjNeuAcα1→3Galβ1-3GalNAc-O-Ser/ThrUnknownBlacks > whites
    ↑6
    (±Fuc-)Galβ1-3/4GlcNAcβ1
    CadGalNAcβ1-4ResistantRare, GM2 active
    〉 Galβ1→3GalNAc-O-Ser/Thr
    NeuAcα2-3 ↑6
    NeuAcα2
    TGalβ1→3GalNAc-O-Ser/ThrResistantNeuraminidase
    TnGalNAc-O-Ser/ThrResistantRare
    • ↵a Sensitivity of red cells to P. falciparum infection in vitro.

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Blood Groups in Infection and Host Susceptibility
Laura Cooling
Clinical Microbiology Reviews Jun 2015, 28 (3) 801-870; DOI: 10.1128/CMR.00109-14

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Blood Groups in Infection and Host Susceptibility
Laura Cooling
Clinical Microbiology Reviews Jun 2015, 28 (3) 801-870; DOI: 10.1128/CMR.00109-14
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  • Top
  • Article
    • SUMMARY
    • INTRODUCTION
    • ABO, LEWIS, AND SECRETOR BLOOD GROUPS
    • LKE AND P1PK, GLOB, AND FORS BLOOD GROUP SYSTEMS
    • DUFFY BLOOD GROUP
    • DIEGO BLOOD GROUP
    • MNSs BLOOD GROUP
    • GERBICH BLOOD GROUP
    • KNOPS BLOOD GROUP
    • OK BLOOD GROUP
    • CROMER BLOOD GROUP
    • INDIAN BLOOD GROUP
    • GIL BLOOD GROUP
    • KELL BLOOD GROUP
    • RAPH BLOOD GROUP
    • ACKNOWLEDGMENT
    • REFERENCES
    • Author Bios
  • Figures & Data
  • Info & Metrics
  • PDF

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