Other Blood Group Systems, Human Leukocyte Antigens, and Platelet Antigen

Kell Blood Group System

• Similar to the Rh system

• 2 major antigens

  • K (K1): < 9% of pop

  • k (K2/cellano): >90% pop

• K and k antigens are antithetical

• Well developed at birth

• K (K1) antigen is very immunogenic → Ab production

Other Kell Antigens

Other antithetical antigens:

• Analogous to the Rh system: C/c and E/e

• Kp antigens

• Js antigens

Kp antigens

• Kpa: low-frequency antigen (only 2%)

• Kpb: high-frequency antigen (99.9%)

Js antigens

• Js-a (20% in blacks, 0.1% in Caucasians)

• Js-b = high-frequency antigen (80% to 100%)

Kell Antigens are sensitive to? why?

the disulfide-bonded regions on the glycoproteins makes them sensitive to sulfhydryl reagents (2-ME, DTT, AET)

K0 or Kell-null Phenotype

• Lacks all Kell system antigens (K0K0)

• Expresses related Kx antigen

• RBC immune stimulation, K0 individuals → anti-Ku

  • (Ku is on RBCs that have Kell antigens)

Kell Genetics

• Sets of alleles include

  • K and k

  • Kp-a and Kp-b

  • Js-a and Js-b

  • KEL11 & KEL17 (Wk-a)

• High-incidence alleles: k, Kp-b, Js-b, and Kel11

• Low-incidence alleles: K, Kp-a, Js-a, Kel17

K-k, Kp-a/Kp-b, Js-a/Js-b, Wk-a

Antigens Kell Group

Common Phenotypes and Frequencies in the Kell Blood Group System

Kell Antibodies

• IgG class

• RBC stimulation (transfusion or pregnancy)

• Agglutinate best in IAT

• Usually do not bind complement

• related to HTRS and HDFN

• No effect when treated w/ enzymes

• Anti-K (K1) most common

What is the most common Kell Ab?

Anti-K (K1) most common

Kx Blood Group System

• Individuals who lack Kx antigen → RBC abnormalities (McLeod phenotype)

• Seen in males bc it is inherited on

  the X chromosome

• phenotypically related to Kell (not genetically similar)

McLeod Syndrome

• McLeod phenotype

• Symptoms:

  • RBC abnormalities

  • Muscular and neurologic defects

  • Increased creatine kinase

• Associated with chronic granulomatous disease

  • Impaired phagocytosis (WBCs engulf but cannot kill)

Duffy Blood Group System

• Antigens are well developed at birth

• Destroyed by enzymes

• Fya and Fyb

  • Codominant alleles

  • Most important for transfusion purposes

Fya and Fyb

antigens in Duffy group

Duffy Antibodies

Anti-Fya and anti-Fyb Abs

• IgG

• Do not bind complement

• Stimulated by transfusion or pregnancy (not a common cause of HDFN)

• Do not react with enzyme-treated RBCs

Duffy System and Malaria

Most African Americans have the Fy(a–b–) phenotype.

• Plasmodium knowlesi and Plasmodium vivax cannot invade Fy(a–b–) red blood cells.

• Fya and Fyb antigens serve as receptors for merozoite on RBCs

• high frequency of Fy(a–b–) in West and Central Africans = selective evolution

Jka, Jkb, and Jk3

antigens in Kidd Blood group

Kidd Blood Group System

• 3 antigens: Jka, Jkb, and Jk3

  • in US: ~51% blacks = Jk(a+b–)

  • In US: ~50.3% whites = Jk(a+b+)

• Jk3 is present whenever Jka and Jkb are present

• Kidd null phenotypes: Jk(a–b–)

• Show Dosage

• Enhanced by enzymes

Kidd null phenotypes: Jk(a–b–)

• Usually seen in individuals from the Far East or Pacific Islands (rare)

• May produce anti-Jk3 antibody

• RBCs are resistant to 2M urea

Kidd Antibodies

Anti-Jk-a & Anti-Jk-b

Kidd Antibodies Key Details

• IgG

• Clinically significant

• May bind complement

• Implicated in HTRs and HDFN

• Common cause of delayed HTRs

• Usually appear with other antibodies when detected

• Use of enhancement enzymes: PEG, LISS

HTR and HDFN are both..

complications involving RBC destruction

Lutheran Blood Group System

• 19 antigens exist (chromosome 19)

• Weakly expressed on cord blood cells

• Most are high-incidence antigens; antibodies are rare

• Primary antigens include Lu-a and Lu-b

  • Lu-null phenotype rare, inherited recessively

• Not affected by enzymes (like kell)

Lutheran Antibodies and Antigens

• Antibodies: Anti-Lu-a, Anti-Lu-b

• Antigens: Lu-a, Lu-b

Anti-Lu-a

• Lutheran Ab

• May occur without RBC stimulation

• IgM and IgG

• Reacts best at room temp.

• Shows mixed-field pattern

• NOT clinically significant

  • low incidence

Anti-Lu-b

• Lutheran Ab

• Rare due to high incidence of antigen

• IgG

• Reacts AHG

• Shows mixed-field pattern

• Associated with transfusion reactions

  (clinically significant)

Lewis Blood Group System

• Lewis antigens are found in secretions (glycoproteins) and plasma (glycolipids)

• glycolipids adsorb onto the RBC membrane

Lewis Antigens

• Le-a and Le-b are not alleles

• Lewis system depends on Hh, Se, and Le genes

• le, h, and se do not produce products

• if the Le gene is inherited → Le-a substance is produced

• Le, H, and Se genes must all be inherited to convert Le-a to Le-bLe(a+b+)

• RBCs are rare

Lewis Genes and Red Cell Phenotypes

Lewis Antibodies

• produced by Le(a–b–)

• IgM

• Not clinically significant

• Agglutination possible at IS, 37°C, and AHG

• Enzymes enhance anti-Leb reactivity

• Anti-Lea binds complement; may cause hemolysis in vitro

• Neutralization confirm presence or eliminate reactions w the Ab

I Blood Group System i Antigen

• NOT antithetical

• form on the precursor A, B, and H chains of RBCs

• Newborns have i antigen

• Adults have I antigen

• i antigen (linear) converts to I antigen (branched) as a child matures (abt 2 yrs)

I Antibodies

• Cold-reacting, IgM, bind complement

• Not clinically significant

• Usually autoantibody (autoanti-I)

• Alloanti-I is rare

• Reactions avoided by prewarming

• Reacts as compound antibody

  • Often found as an anti-IH

  • Stronger agglutination with RBCs having many H sites (O and A2)

Autoanti-I diseases

• Mycoplasma pneumoniae

• Cold hemagglutinin disease

Anti-i diseases

• Infectious mononucleosis

• Lymphoproliferative disease

• Cold hemagglutinin disease (occasionally)

P1PK Blood Group System

• P1PK blood group system: P1 and P-k

• P1 antigen is detected in plasma and hydatid cyst fluid

• Globoside blood group system: P antigen

• Globoside blood group collection: Luke (LKE) and PX2 antigens

• high-frequency antigens: P, Pk, and LKE antigens

P Antigens and Antibodies Characterstics

P Antibodies

MNS Blood Group System

M & N

• Glycophorin A

• Show dosage: Homozygous inheritance

  enhances agglutination [(M+N–) or (M–N+)

S, s, and U

• Glycophorin B

• U antigen: resent when S or s is inherited

MNS Antibodies

• Anti-M

  • IgM & IgG

  • rarely encountered in HDFN

  • rxns depends on pH

• Anti-N

  • Rare IgM

  • N-like Abs in dialysis patients

• Anti-S/s/U

  • Clinically significant IgG

  • Anti U is rare but can be found in S-s- (black pop.)

Miscellaneous Blood Groups and Antigens

HLAs

• Found on leukocytes and tissue ells

• Abs produced from transfusion and/or pregnancy

• refractoriness and transfusion rxns

• assess risk factors for disease susceptibility

• matching for organ and HPC transplants

Inheritance of HLAs

• Genes that code for HLA are part of the MHC

• MHC genes (Class I,II, III)

• Individuals inherit one haplotype (closely linked genes) from each parent

• Ags are # followed by lettered

MHC gene classes

• Class I: platelets, leukocytes, nucleated cells

• Class II: macrophages, dendritic cells, B cells

• Class III: code for complement and cytokines

HLA testing

Serologic HLA identification uses lymphocytotoxicity testing: complement and dye indicate Ag-Ab complex

Antibody Detection and Identification

• Matching HLAs in patients with existing antibodies for graft survival

• Patients sensitized to HLAs by the following exposures:

  • Pregnancy

  • Blood transfusions

  • Previous transplant

HPC Transplants

• HPCS obtained from bone marrow, peripheral blood, and cord blood

• used to treat diseases (ex: aplastic anemia, leukemia, lymphoma and Hodgkin’s disease )

• HLA matching at the allelic level to rejection and GVH disease

Platelet Antigens

• Platelet proteins can elicit immune responses

• Antibodies to platelets →

  • NAIT: destruction of newborn platelets by maternal antibody

  • PTP: destruction of platelets after transfusion

• most common platelet antibody is against HPA-1a (or P1A1)