IMHM311-LEC

WEEK #9: OTHER BLOOD GROUP SYSTEM PART 2

MIDTERM I SECOND SEMESTER
I BLOOD GROUP SYSTEM KELL ANTIGENS
Ii ANTIGENS • Immunogenic, K is rated second only to D in terms of
• At birth, infant red cells are rich in “i” (small letter i); Capital immunogenicity
“I” is almost undetectable. o D antigen - most immunogenic
o The antigens are best introduced by classic serologic o d antigen - least immunogenic
facts. • Well developed at birth: Kell, MNSs, Kidd, Duffy
o Both I and i are high-incidence antigens, but they are o The capital K antigen can be detected on fetal RBCs
expressed in a reciprocal relationship that is as early as 10 weeks (small letter k at 7 weeks)
developmentally regulated. • Not Destroyed by enzymes, but it can be destroyed when
• During the first 18 months of life, the quantity of “i” slowly trypsin and chymotrypsin are used in combination.
decreases as “I” increases until adult proportions are o K = Kell
reached, adult red cells are rich in “I” and only trace amount o k = Cellano
of “i” antigen. o Kpa = Penney
o Capital I is dominant o Kpb = Rautenberg
o Some people appear not to change their i status after o Jsa = Sutter
birth. o Jsb = Matthews
▪ They become the rare adult i or the negative KELL SYSTEM PHENOTYPE FREQUENCIES
phenotype (i-) Phenotype Whites (%) Blacks (%)
o Adult i RBCs generally express more i antigen than K-k+ 91.0 96.5
do cord RBCs. K+k+ 8.8 3.5
Anti-I K+k- 0.2 <0.1
• Common autoantibody that can be classified as benign or Kp(a+b-) <0.1 0
pathologic. Kp(a+b+) 2.3 Rare
• Demonstrates strong reactions with adult cells and weak Kp(a-b+) 97.7 100
reactions with cord cells. Js(a+b-) 0 1
• Not associated with HDN (hemolytic disease of the Js(a+b+) Rare 19
newborn) due to poorly expresses on infant red cells. Js(a-b+) 100 80
BENIGN Anti-I
• Found in serum of normal individual. Anti- K
o Causes interference in reverse typing (since • Other than ABO and Rh antibodies, anti-K is considered as
serum/plasma is the specimen of choice) the most common antibody seen in blood bank.
o Primarily, in reverse typing the benign anti-I would
• Usually an IgG→ reacts at AHG phase.
cause the interfering factors
o Mechanism of IgG → it has the ability to cross with the
• Not associated with in vivo red cell destruction. placenta
• Weak, naturally occurring saline-reactive IgM agglutin that • Severe hemolytic transfusion reaction
reacts at 4°C
• Associated in severe hemolytic disease of the newborn
PATHOLOGIC Anti-I
(HDN) or Erythroblastosis fetalis
• Potent IgM agglutinins, reacting up to 30°C or 32°C Kx Antigen
• Attach in vivo and cause autoagglutination and vascular • Kx is present on all RBCs except those of the rare McLeod
occlusion or intravascular hemolysis phenotype (possible to be encountered in Kell blood group
• Associated with conditions such: system)
o CAD (cold agglutinin disease) • Inverse relationship with K antigen.
o CHD (cold hemagglutinin disease)
• Encoded on the genes located on the X chromosome.
o PAP (primary atypical pneumonia)
McLeod PHENOTYPE
Autoanti-I
• Rare phenotype; unusual phenotype
• Patients with Mycoplasma pneumonia often develop strong
o McLeod Phenotype was named after the donor
agglutinins with I specificity as a cross-reactive response to
• Appeared to Kell null but they demonstrate weak
Mycoplasma antigen
expression of k, Kpb and Jsb detectable by adsorption-
o and can experience a transient episode of acute abrupt
elution methods.
hemolysis just as the infection begins to resolve.
o Walking pneumonia (mycoplasma pneumoniae) • X-linked inheritance through a carrier mother.
• Listeria monocytogenes organism from a patient with cold • Abnormal red cell morphology
autoimmune haemolytic anemia has been reported to absorb o Acanthocytes→ variation in red cell Shape.
anti-I and stimulate its production in rabbits ▪ Patient with Mcleod phenotype have a chronic
but well compensated hemolytic anemia
• Production of autoanti-I is also associated with infectious
characterized by reticulocytosis,
mononucleosis, reticuloses, myeloid leukemias and
bilirubinemia, splenomegaly and reduced
alcoholic cirrhosis.
serum haptoglobin levels.
o The infectious mononucleosis or IM is caused by EBV
infections or Epstein-Barr virus infections • Associated with X-Linked CGD (Chronic Granulomatous
Anti-I Disease)
o CGD is characterized by the inability of phagocytes to
• Most autoanti-I are IgM
make NADH-oxidase, an enzyme important in
• React best with saline suspended cells at 4°C
generating H2O2, which is used to kill ingested
• Seen in: bacteria.
o Infectious mononucleosis (IM) ▪ Phagocyte - cell eating cell
o Disease of RES (Alcoholic Cirrhosis, Myeloid ▪ H2O2 - hydrogen peroxide
Leukemia, Reticuloses) o Afflicted children die at an early age from over-
▪ RES means Reticuloendothelial System whelming infections.
o Not all males with the McLeod phenotype have
KELL BLOOD GROUP SYSTEM CGD, nor do all patients with CGD have the McLeod
• Anti-K was identified in 1946➔ In the serum of Mrs. phenotype.
Kellaher.
o The antibody reacted with the RBCs of her newborn DUFFY BLOOD GROUP SYSTEM
infant, her older daughter, her husband, and about 7 • was named for Mr. Duffy, a multiply transfused hemophiliac
percent of the random population who in 1950 was found to have the first described example
▪ k and K → antithetical antigens or antithetical of anti-Fya.
partners o hemophilia - coagulation disorder
• 1949➔ Levine et al describe anti-k (Cellano) ▪ anti-hemophilic factor na sinasalin or mga
• 1957 and 1958➔ discovery of the antithetical antigens Kpa cryoprecipitated AHF
and Kpb • A year later➔ discovery of its antithetical antigen Fyb.
• 1958➔ Giblett discovered Jsa • Antithetical antigen in Duffy → Fya and Fyb
• 1963→ Walker et al discovered Jsb ➔ antithetical to Jsa Fya and Fyb
• 1957 ➔ null phenotype discovered K0 • Well developed at birth
• 1961➔ Allen et al described Mcleod phenotype • Destroyed by common proteolytic enzymes or inactivate by
o Expression very weak on McLeod phenotype cells proteolytic enzymes: MNSs, Duffy, Xga
•

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 WEEK 9: OTHER BLOOD GROUP SYSTEM PART 2
FREQUENCY OF DUFFY PHENOTYPES Lua and Lub Antigens
Phenotype Whites American blacks Chinese • Although the antigens have been detected on fetal RBCs as
(%) (%) (%)76 early as 10 to 12 weeks of gestation, they are poorly
Fy(a+b-) 17 9 90.8 developed at birth and do not reach adult levels until age
Fy(a+b+) 49 1 8.9 15 years.
Fy(a-b+) 34 22 0.3 Anti-Lua
Fy(a-b-) Very rare 68 0 • Most naturally occurring saline agglutinins that react better
at room temperatures than 37°C
Anti-Fya & Anti-Fyb • Ig class could be of IgA, IgM or IgG in nature.
• Usually IgG and react best at the antiglobulin phase • Associated with mild cases of HDN.
• Activity is enhanced in low ionic strength medium Anti-Lub
o Enhancement medium such as LISS (Low Ionic • Most are IgG that reacts at 37°C
Strength solution) • Associated with mild cases of HDN.
▪ Other enhancement medium: 22% Bovine
Albumin, PEG (Polyethylene Glycol) Diego Blood Group System
• Do not react with enzyme-treated red cells • The Diego system is composed of two sets of independent
• Associated with hemolytic transfusion reactions, pairs of antithetical antigens: Dia/Dib and Wra/Wrb.
although hemolysis is not often severe • Dia antigen is useful tool in anthropologic studies of
Mongolian ancestry.
KIDD BLOOD GROUP SYSTEM • Dia and Dib➔ located on the anion exchange protein (AE-
• Discovered in the serum of a pregnant patient named Mrs. 1).
Kidd, whose infant had HDN. o which is an integral transport protein involved in the
• The antibody, named: Anti-Jka. anion exchange of bicarbonate for chloride in the
o The antithetical partner is: Jkb. RBC membrane.
• Null phenotype➔ Jk (a-b-) o Mutations in AE-1 can result in HS (hereditary
Jka and Jkb Antigens spherocytosis), congenital acanthocytosis,
• Jka can be detected on fetal RBCs as early as 11 weeks Southeast Asian ovalocytosis.
and 7 weeks for Jkb
• Well developed at birth: MNSs, Kell, Kidd, Duffy Cartwright Blood Group system
• The Kidd antigens are not very immunogenic. • Composed of two antigens → Yta and Ytb antigens.
• Enhanced by proteolytic enzyme • Antibodies were IgG in nature
• Associated with transfusion reaction:
FREQUENCY OF KIDD PHENOTYPES o However, cases are documented of Yta antigen–
Phenotype Whites (%) Blacks (%) Asians negative patients receiving Yta antigen–positive
(%) RBCs without adverse consequences.
Jk(a+b-) 28 57 23 • No reports have related YT antibodies to HDN.
Jk(a+b+) 49 34 50
Xg Blood Group System
Jk(a-b+) 23 9 27
• Xga antigen
Jk(a-b-) Exceedingly Exceedingly 0.9<0.1
o Xg Phenotype: Xg(a+) and Xg(a-)
rare rare
• No known antithetical partner.
Anti-Jka and Anti-Jkb • The gene is located on the Short arm of the X
chromosome.
• Have notorious reputation in the blood bank
X-linked inheritance (Kx and Xg)
o Difficult to detect.
• Xga → does not appear to be a good immunogen; clinically
• Demonstrate dosage:
insignificant
o Many anti-Jka and anti-Jkb react more strongly with
RBCs that carry a double dose of the respective antigen • Anti-Xga → IgG
and may not react with Jk (a+b+) RBCs o No known transfusion reaction cases nor HDN.
• IgG in nature
Scianna Blood Group System
• Activity is enhanced by using LISS or PEG ➔ for enhanced
• Sc1 and Sc2 antithetical antigens, Sc3 and Radin (Rd)
IgG attachment
antigen.
• Associated with severe HDN & delayed type of HTR o The SC system is composed of the Sc1 and Sc2
(hemolytic transfusion reaction) antithetical alleles, the high-incidence Sc3, and the low-
• Autoantibodies to Kidd ➔ rare but they have been associated incidence Radin (Rd) antigen.
with AIHA (autoimmune hemolytic anemia) • The Scianna antigens are shown to be expressed by the
o Some are drug induced: Patient taking RBC adhesion protein ERMAP in humans
METHYLDOPA or Chlorpropamide-dependent o ERMAP (Erythroblast membrane Associated
patients. protein)
▪ Methyldopa - hypertension medicine
▪ Chlorpropamide - used as a diabetes medication Dombrock Blood Group
• Doa, Dob, Hy (Holley), Gya (Gregory), Joa
LUTHERAN BLOOD GROUP SYSTEM • The null phenotype in the Dombrock system demonstrates
• The new antibody was named Lutheran, a misinterpretation an absence of Doa, Dob, Gya, Hy, and Joa antigens.
of the donor’s name, Luteran. • Antigens resides on the glycosylphosphatidylinositol
• 1945 - First recognized when an antibody (anti-Lua) was (GPI)-linked glycoprotein that anchors them to the RBC
discovered in the serum of a patient with Lupus membrane.
Erythematosus following transfusion of a unit of blood o Total absence of DO expression is observed in
carrying the corresponding antigen. paroxysmal nocturnal hemoglobinuria III RBCs,
o A year after, antithetical antigen was discovered → which are deficient in all GPI-anchored
anti-Lub glycoproteins, DAF (Decay accelerating factor), as
o Most individuals are Lub+ (dominant) and only a few well as CDw108.
Lua+ ▪ CDw108 (cluster of differentiation w108)
• 1956 → Cutbush and Chanarin described anti-Lub, which • Associated with PNH: Dombrock, Cromer, JMH (John
defined the antithetical partner to Lua. Milton Hagen)
• 1961➔ Crawford et al discovered the first Lu(a-b-)
phenotype. Colton Blood Group System
• Coa, Cob, and Co3
FREQUENCY OF • These antigens are located on the integral transmembrane
LUTHERAN PHENOTYPES protein known as Aquaporin-1 (AQP1)
Phenotype Whites (%) o which forms primary plasma membrane water
Lu(a+b-) 0.15 channels for the regulation of osmotic water transport.
Lu(a+b+) 7.5
Lu(a-b+) 92.35 Chido/Rodgers Blood Group System
Lu(a-b-) Very rare • Nine antigens → six Chido antigens, two Rodgers
antigens, and the WH antigen.
• Major blood group system: ABO, RH, KELL, KIDD, o CH1, CH2, CH3, RG1, and RG2 are described as high-
DUFFY, MNSs, p, LEWIS, LUTHERAN incidence antigens
• Not an integral red cell membrane antigen

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 WEEK 9: OTHER BLOOD GROUP SYSTEM PART 2
o Reside on C4 complement component
o Antibody reactions seen in transfusion of
plasma/platelets
• Null CH and RG phenotypes→ seen in patient with C4
deletion
o Associated with a number of autoimmune diseases
such as systemic lupus erythematosus, Graves’
disease, and rheumatoid arthritis

Gerbich Blood Group System

• Consist of three high-incidence antigens (Ge2, Ge3, and
Ge4) and four low-incidence antigens (Wb, Lsa, Ana, and
Dha).
• Expressed on RBC membrane sialoglycoproteins
glycophorins C (GPC) and/or glycophorin D (GPD)
o GPC and GPD are associated with the RBC membrane
band 4.1, which is integral for maintaining normal
erythrocyte skeleton and shape.

Cromer Blood Group System

• Composed of 8 high-incidence antigen and three low-
incidence antigens.
o 8 high-incidence: Cra, Tca, Dra, Esa, IFC, UMC, Wesp,
GUTI
o 3 low-incidence: Tcb, Tcc, and WESa
• Null phenotypes “Inab(-)” → no CROM antigens,
deficient/absent DAF
o A total absence of Cromer expression is also observed
in paroxysmal nocturnal hemoglobinuria III RBCs,
which are deficient in all GPI anchored
glycoproteins, DAF (Decay accelerating factor), as
well as CDw108.
▪ paroxysmal nocturnal hemoglobinuria is
associated with Dombrock, Cromer, JMH (John
Milton Hagen)

Knops and Indian Blood Group System

• Knops Blood Group System➔ Composed of eight
antigens.
o 8 antigens: Kna (Knops), Knb, McCa (McCoy), Sl1
(Swain-Langley), Yka (York), McCb, Sl2 (Vil), and Sl3.
o Three pairs of antithetical alleles:
▪ Kna and Knb
▪ McCa and McCb
▪ Sl1 and Sl2
• Indian Blood Group System➔ Composed of two
antithetical antigens.
o Ina→ low-incidence antigen
o Inb→ high-incidence antigen
▪ Inb is noted in 96 percent of whites and 96 percent
of Indians.
• In (Lu) gene → depressed expression of Inb in individual
presenting with Lu (a-b-) phenotype.
• The IN antigens are carried on the the CD44 glycoprotein,
which is present on most tissues.

John Milton Hagen Blood Group System

• Only one antigen ➔ JMH antigen
• A total absence of JMH expression is also observed in
paroxysmal nocturnal hemoglobinuria III RBCs, which are
deficient in all GPI anchored glycoproteins, DAF (Decay
accelerating factor), as well as CDw108.
o paroxysmal nocturnal hemoglobinuria is associated
with Dombrock, Cromer, JMH (John Milton Hagen)

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