(pt 2) exam #3 - immunohematology (cls 544)

other common blood group systems

where are most blood group genes located?

on autosomal chromosomes

• Some genes code for structures carrying more than one antigen

• Most blood group systems alleles exhibit co-dominant expression

  • Antigen expressed when gene present and one gene does not suppress another

    • ex: inheritance of K/k alleles will result in both being expressed on the individual's RBCs

phenotype

• The result obtained from testing RBCs with known reagent antisera

• Phenotype results estimate genotype

alleles vs antithetical

• Alleles

  • Alternative alleles at a single gene locus

  • Designated by italics

• Antithetical

  • When locus can have different alleles, there are corresponding antigens

null phenotype 

occurs when RBC has no detectable antigens in system

• where paired chromosomes carry the same silent allele → e.g. Lu (a-b-)

• in some blood group systems, the null phenotype may result in RBC abnormalities

silent/amorphic alleles

rare—alleles exist but do not produce any antigen

regulator/modifying genes

• Seen in some blood groups—alter antigen expression

  • e.g. dominant type of Lu(a-b-) suppresses expression of all other Lutheran blood group antigens including other blood group antigens P1 and I

    • This gene is inherited independently from genes coding for Lutheran, P1, and i antigens

writing convetions for genes and antigens

• Genes

  • Written in italics or underlined; their allele number or letter is always superscript

• Antigen names

  • Regular type without italics or underlining

  • Some antigens have numbers or superscript letters

antigen and phenotype nomenclature

• For letter antigens, a plus sign (+) or minus (-) written on the same line as the antigen is used to designate that the antigen is present or absent

  • e.g., M+, K-

• For antigens that have superscripts: the letter of the superscript is placed in parentheses on the same line as the letter defining the antigen

  • e.g., Fy^a -> Fy (a+), Jk^a -> Jk (a-)

• For antithetical antigens: both results are written with the parentheses

  • e.g., Fy^a and Fy^b -> Fy(a-b+)

antigen/antibody nomenclature

• antigens with a numerical designation, the letters(s) defining the system is followed by a colon, then the number representing the antigen. No plus sign written to denote presence of antigen, but a minus sign is written before the negative result. Multiple results are separated by a comma

  • e.g. Sc: -1,2

• Antibodies are described by their antigen notation with the prefix "anti-," including a hyphen before the antigen symbol

  • e.g., anti-C, anti-k

history of ISBT nomenclature

• Related antigens placed in blood group system once genetic basis confirmed

• Antigens where genetic basis unknown placed in collections

• Each antigen given a six-digit number

  • First three digits – identify the system, collection, or series

  • Second three digits – identify the antigen

  • Numbered sequentially in order of discovery

  • Each system has an alphabetical symbol

• To date, 48 blood group systems have been identified 

antigen collections

antigens that have a biochemical, serologic, or genetic relationship but do not meet the criteria for a system

• Antigens classified as a collection are assigned a 200 number

• All remaining RBC antigens that are not associated with a system or collection are catalogued into the 700 series of low-prevalence antigens or the 901 series of high-prevalence antigens

  • Low prevalence antigens occur in less than 1-2% of the population

  • High prevalence antigens occur in greater than 90% of the population

clinically significant antibodies

• can cause shortened survival of transfused RBCs

  • Hemolytic transfusion reaction (HTR)

  • Hemolytic disease of the fetus and newborn (HDFN)

list of commonly encountered antibodies

• Rh, Kell, Duffy, Kidd, MNS, and Lutheran

• Lewis, P1, I

carbohydrate blood groups (3)

include: Lewis, P, and I

• Like ABH antigens, these are NOT encoded directly by genes

• The genes encode specific glycosyltransferases that in turn synthesize the carbohydrate epitopes by sequential addition of sugars to a precursor

• Carbohydrates (sugars) attached to glycoproteins or glycolipids

(general) lewis blood group system (LE)

• ISBT system symbol: LE, Number: 007

• Lewis antigens are NOT intrinsic to RBC membrane (unique)

  • Adsorbed from plasma onto RBC membrane

• Le gene (FUT3) codes for L-fucosyltransferase = adds L-fucose to type 1 precursor chains

  • Le gene needed for expression of Le^a substance

  • Le and Se genes (FUT2) needed for formation of Le^b substance

• Antigens result from presence of Lewis gene

  • Poorly expressed at birth, 6 antigens

(LE blood group) where are the lewis ANTIGENS located?

on Type 1 glycosphingolipids that are passively adsorbed onto the RBC membrane from the plasma

• Lewis antigens of primary concern: Le^a and Le^b

  • Not antithetical antigens (not alternative alleles of a single gene)

• Result from the interaction between two fucosyltransferases encoded by independent genes → Le (FUT3) and Se (FUT2)

  • Two alleles at the Lewis locus

    • Le + amorph le

  • Two alleles at the Secretor locus

    • Se + amorph se

(LE blood group) where are the Le and Se GENES located?

CHROMOSOME 19

• Le gene must be present for a precursor substance to be converted to Le^a

• Se gene must be present for conversion to Le^b

• Individuals with Le(a+) mostly non-secretors of ABH antigens

(LE blood group) possible phenotypes

caused by interaction between Le and Se gene 

• Le(a+b-): ABH non-secretors

• Le(a-b+): ABH secretors

• Le(a-b-): More frequent among African American population, either secretors or non-secretors

• Le(a+b+): More frequent among Asian population

(LE blood group) expression of lewis antigens

• Depending upon the genes inherited, both Le^a and Le^b glycoproteins will be present in the saliva of newborns

  • Lewis glycolipids are NOT detectable in the plasma until about 10 days after birth

  • Not expressed on cord RBCs and diminished on maternal RBCs during pregnancy

• Found on lymphocytes, platelets and other tissues such as pancreas, stomach, intestine, skeletal muscle, renal cortex, and adrenal glands

• Soluble Le antigens found in saliva as glycoproteins (RBC antigens are glycolipids)

(LE blood group) effect of enzyme treatment on lewis antibodies?

reactivity of Lewis antibodies enhanced by testing with enzyme-treated RBCs

(LE blood group) development/inheritence of lewis antigens

• Inheritance of Le and Se gene

  • Inherit BOTH Le and Se genes

    • Le(a-b-) at birth →Le(a+b-) after 10 days →Le(a+b+) → Le(a-b+) also known as the “true Lewis phenotype” after 6 years

  • Inherit Le and sese genes

    • Le(a-b-) at birth →Le(a+b-) after 10 days

    • Le(a+b-) persists through rest of life

  • Inherit lele genes

    • Le(a-b-) phenotype at birth and throughout rest of life

(LE blood group) changes in lewis phenotype may be caused by?

• Pregnancy

  • Decreased Lewis antigens on RBC

  • Le(a-b-)

  • Increased incidence of formation of Lewis antibodies

  • Transient change 

  • Lewis antigens easily dissociate from red blood cell membrane

(LE blood group) lewis blood group antibodies

• Frequently naturally occurring antibodies made by Le(a-b-) persons

  • Occur without any known RBC stimulus

• Generally IgM, do not cross placenta, and can activate complement

• Anti-Le^a and Anti-Le^b may occur together

  • May be seen in pregnant women who transiently exhibit Le(a-b-) phenotype

• Anti-Le^a more commonly encountered, can be clinically significant, may cause in vitro hemolysis

• Lewis antibodies neutralized by Lewis substances in plasma or saliva

(general) P blood group system (P1Pk)

• Traditionally comprised of P, P1, and P^k and later, Luke (Lke), PX2, ExtB, and NOR

• Currently the ISBT nomenclature are assigned as follows:

  • P1, P^k and NOR assigned to P1PK blood group system (P1Pk, 003)

  • P, ExtB, and PX2 to Globoside Blood Group System (GLOB, 028)

  • LKE is assigned to the 901 series (901017)

• Overall, referred to as the "P blood group"

• Two common phenotypes in the P blood group system are P₁ and P₂

  • Three rare phenotypes: p, P₁^k, and P₂^k

(P blood group) main phenotypes associated with this system (3)

• P₁ Phenotype (P1, P, P^k antigens)

  • RBCs react with anti-P1 and anti-P

• P₂ Phenotype (P, P^k antigens)

  • RBCs react with anti-P

• p (P null) Phenotype

  • Rare, RBCs do not react with anti-P1, anti-P, or anti-P^k

  • Make anti-P, P1, P^k

(P blood group) where are the P1Pk and P genes located?

• P1PK (located on chromosome 22) and P (located on chromosome 3) genes are inherited independently

• Antibodies can be clinically insignificant OR potently hemolytic

(P blood group) P1 antigen

• poorly expressed at birth—can take up to 7 years to be fully expressed on RBCs

  • Strength of antigen expression may vary based on ethnicity → stronger expressed noted in AA population

  • Deteriorates rapidly in storage

(P blood group) anti-P1 antibody

• Common, naturally occurring IgM antibody in the sera of P1 individuals

• Reacts below 37C = clinically insignificant

  • IgG forms are rare = not associated with HDFN

  • Rare reactions at 37C may result in both immediate and delayed HTRs

  • Neutralized by P1 substance, hydatid cyst fluid

• Transfusion considerations

  • Provide units crossmatch-compatible at 37C/AHG without typing for P1 is acceptable!

(P blood group) expression of P blood group antigens

• Similar to ABH antigens, synthesized by sequential action of glycosyltransferases--exist as glycosphingolipids

• P₁, P, or P^k may be found on RBCs, lymphocytes, granulocytes, and monocytes

• P can be found on platelets, epithelial cells, and fibroblasts

• P and P^k found in plasma as glycosphingolipids and as glycoproteins in hydatid cyst fluid

• Antigens have NOT been identified in secretions

(P blood group) effect of enzyme treatment

reactivity of P blood group antibodies enhanced with enzyme treated RBCs

(P blood group) luke (LKS) antigen

• Phenotypically-related because the antibody reacts with all RBCs except 2% of P₁ and P₂ phenotypes and rare p and P^k phenotypes

• All individuals with the p and P^k phenotype are referred to as Luke(-)

(P blood group) disease associations

• Parasitic infections → anti-P1

• Early abortion → anti-PP1P^k or anti-P

• PCH → autoanti-P

• P is the receptor of human parovirus B19

• P^k provides some protection against HIV infection of PMNs, Shiga toxin receptor

(P blood group antibodies) anti-PP1P^k

• Produced by p individuals early in life without RBC sensitization

• Reacts with all RBCs except those of the p phenotype

• IgM and IgG--react at a wide thermal range

• Can bind complement--cause severe HTRs and HDFN

• Associated with increased incidence of spontaneous abortions early in pregnancy

(P blood group antibodies) alloanti-P

naturally occurring alloantibody in the sera of P^k individuals—-rare but clinically significant in transfusion

(P blood group antibodies) autoanti-P

associated with paroxysmal cold hemoglobinuria (PCH)

• Anti-P associated with the cold-reactive IgG autoantibody in patients with PCH (biphasic)

• Does not react in routine serological testing—identified via the Donath-Landsteiner test

• Post viral infection or tertiary syphilis

(P blood group) testing considerations

• Soluble P1 antigen is available as a reagent

  • Can be used in antibody identification to neutralize (inhibit) anti-P1

• Anti-P1 is considered a RT-nuisance antibody

  • Elimination of IS phase

  • Use of monospecific anti-IgG in IAT

  • Use of non-tube testing techniques

(general) I blood group system (I) & i antigen

• "I" stands for "individuality", symbol I, system number 027; i antigen, Ii Collection 207

  • Located on chromosome 6

• I and i antigens are NOT antithetical, reciprocal relationship

• Most adult RBCs are rich in I antigen--trace amounts of i antigen

• At birth, infant RBCs are rich in i antigen--I antigen undetectable

  • The i antigen on infant RBCs convert to I antigen over an 18 month period

• Antibodies usually IgM autoantibodies, enhanced by enzyme treatment

• Soluble substances in plasma, secretions such as milk and amniotic fluid

(I blood group antibodies) anti-I

benign, weak, naturally occurring IgM autoagglutinin that is usually detectable at 4 C

• Anti-I = common autoantibody that can be found virtually all sera

  • Testing the sera at 4C and against enzyme-treated RBCs may be required to detect the reactivity

• The production of autoanti-I may be stimulated by microorganisms carrying I-like antigen on their RBC surface

  • e.g. patients with mycoplasma pneumoniae

• Anti-I is NOT associated with HDFN

(I blood group antibodies) pathogenic autoanti-I

• Strong IgM cold agglutinin that reacts at 4C and over a wide thermal range up to 30C

• Existence of cold agglutinins in the serum of normal individuals and in patients with acquired hemolytic anemia

• May mask clinically significant antibodies

(I blood group antibodies) autoanti-i

• may present as a rare IgM agglutinin that reacts at 4C

  • Potent examples associated with infectious mononucleosis (Epstein-Barr virus infection)

(reactivity patterns of cold autoantibodies) anti-I

• O, A1, A2, B cells = 4+

• Cord O & A cells: 0

• Bombay (H-): 4+

• I negative cells: 0

(reactivity patterns of cold autoantibodies) anti-i

• O, A1, A2, B cells: 0

• Cord O & A cells: 4+

• Bombay (H-): 0

• I negative cells: 4+

(reactivity patterns of cold autoantibodies) anti-H

• O cells; cord O cells; I neg cells: 4

• A1 cells: 0

• A2 cells: 2

• B cells: 1

• Cord A cells: 2

• Bombay (H-): 0

(reactivity patterns of cold autoantibodies) anti-IH

• O cells: 4

• A1 cells: 0

• A2 cells: 2

• B cells: 1

• Cord O & A cells: 0

• Bombay (H-) & I negative cells: 0

(general) MNS blood group system (MNS)

• includes 50 antigens ; on chromosome 4

• ISBT assigned symbol MNS and number 002

• M and N antigens are found on glycoprotein structures also referred to as glycophorins

  • GYPA gene controls M and N antigen production, antithetical antigens

  • GYPB gene controls S,s, and U antigen production

• MNS antigens are well developed at birth

• MNS antigens all show dosage

(MNS blood group) where are the M and N antigens located?

on Glycophorin A (GPA)

• M & N give a stronger reaction when homozygous, (M+N-) or (M-N+)

• Weaker reactions occur when in the heterozygous state (M+N+)

(MNS blood group) where are S, s, and U antigens located?

• on a smaller glycoprotein called Glycophorin B (GPB)

  • Differentiated by the amino acid at positive 29 on GPB

• U antigen is ALWAYS present when S and s are inherited (high prevalence)

  • About 85% of S-s- individuals are U-negative (RARE)

  • U-negative cells are only found in the African American population

(MNS blood group) effect of enzyme treatment on M & N antigens

due to location on the outer end of GPA, M & N antigens easily destroyed by ficin, papain, bromelin, trypsin, and pronase

(MNS blood group) effect of enzyme treatment on S & s antigens

• Less easily destroyed by enzyme treatment since they are located further down the glycoprotein (less accessible)

  • Can be destroyed by ficin, papain, bromelin, pronase, and chymotrypsin

    • NOT destroyed by trypsin, DTT, AET, chloroquine or glycine-acid EDTA treatment

MNS blood group antibodies (general)

• M and N antibodies are heterogenous

  • Some recognize only specific amino acids; others recognize both amino acids and carbohydrate chains

• Anti-M and Anti-N are cold-reactive saline agglutinins

  • Many examples are naturally occurring saline agglutinins that react below 37C

• Usually IgM

• Do NOT bind complement

• Not clinically significant unless antibodies react at 37C

• Demonstrate dosage

  • e.g. strong anti-M reactions are seen with M+N- RBCs vs M+N+ RBCs

(MNS blood group antibodies) anti-M

• Rarely causes HTRs, HDFN, or decreased red blood cell survival

• More common in children than in adults

• Seen in patients with bacterial infections

(MNS blood group antibodies) anti-N

• Seen in renal patients who were dialyzed on equipment sterilized with formaldehyde (anti-N^f)

• Antibody titer decreased with dialysis treatment stops

(MNS blood group antibodies) anti-S & anti-s

• IgG antibodies

• Reactive at 37C and the antiglobulin (AHG) phase

• Can bind complement—associated with HDFN and HTR

• Dosage effect can be exhibited

• May or may not react with enzyme-treated RBCs

(MNS blood group) transfusion considerations 

• 11% Caucasian and 3% Afriacan American (AA) populations are s-

• 45% Caucasian and 69% AA populations are S-

  • Notably, S-s-U- phenotype is found in AA populations (<1% of AA)

(MNS blood group) GPA- & GPB- deficient phenotypes (3)

RBCs of three rare phenotypes lack either GPA or GPB or both and, consequently lack all MNS antigens that are normally expressed on those structures

• U- phenotype: S-, s-, cells lack GPB

  • U antigen located on GPB; high prevalence antigen

  • U antigen resistant to enzyme treatment

  • Anti-U (IgG) assoc with both HTR and HDFN

• En(a-) phenotype: M-, N-, cells lack GPA

  • En^a located on GPA (high prevalence antigen)

  • Most produce anti-En^a; has caused severe HTRs and HDFN

• M^k phenotype: cells lack both GBA and GPB

  • Rare silent gene (M and N alleles not produced, null phenotype in MNS system)

  • Single, near-complete deletion of both GYPA and GYPB

(MNS blood group) other antibodies

• can usually be grouped into two categories:

  1. Those directed against high-prevalence antigens

  2. Those directed against low-prevalence antigens

• Autoantibodies

  • U and En^a more common

  • Associated with warm-type autoimmune hemolytic anemia

• Disease associations

  • GPA^M receptor for pyelonephritogenic strains of E coli

  • Plasmodium falciparum uses receptors for cell invasion

(general) kell blood group system (KEL)

• ISBT symbol KEL, number 006

  • 38 antigens

  • Kell antigens present on the single gene, KEL located on chromosome 7

  • k (cellano) antigen is high prevalence

• Kx Blood Group System

  • ISBT symbol KX, Number 019, located on X chromosome

  • Kx = high frequency antigen

  • Only known antigen in the Kx blood group system

  • Kell antigens expression greatly reduced when Kx protein is absent

(KEL blood group) kell antigen characteristics

• Cellular distribution of the antigen

  • Found only on RBCs

  • K can be detected on fetal RBCs as early as 10 weeks (!!)

  • Well developed at birth

• Cannot be destroyed with routine blood bank enzymes

  • Can be destroyed with 0.2M DTT, ZZAP, 2-ME, 2-AET, and glycine-acid EDTA

• With the exclusion of ABO, the K antigen is rated second to the D antigen in terms of immunogenicity

(KEL blood group) list of high incidence antigens (3)

k, Kp^b and Js^b antigens all high incidence

(KEL blood group) Kp^a and Kp^c antigens

• Rarely encountered and not routinely tested with antibody identification panels

• Most often detected through incompatible crossmatches of HDFN

• Kp^a and Kp^c are low prevalence mutations of their high-prevalence partner, Kp^b

(KEL blood group) Js^a and Js^b antigens

• Js^a antithetical to the high prevalence antigen, Js^b

• Found in 20% Black population (less than 0.1% Caucasian population)

• Both antigens linked to the Kell system due to K₀ RBCs phenotype of Js(a-b-)

(KEL blood group) major antigens encoded by kell gene

• K1 = K = Kell = 9%

• K2 = k = Cellano = 99.8%

• K3 = Kp^a = Penney = 2%

• K4 = Kp^b = Rautenberg = >99%

• K6 = Js^a = Sutter = <0.1% W 20% B

• K7 = Js^b = Matthews = 99.9 %

• K17 = Wk^a = Weeks = 0.3

• K11 = Cote = >99.9%

• K10 = Ula no allele

• Most common: k/Kp^b/Js^b/K11

kell blood group system antibodies (general)

• Outside of ABO and Rh antibodies, anti-K is the most common antibody encountered in the blood bank

• Anti-K is usually IgG antibody

  • Reactive in the AHG phase

• Most anti-K appear to be induced by pregnancy and transfusion

  • Implicated in severe HDFN (attributed to suppression of erythropoiesis) and severe HTR

• Naturally occurring IgM anti-K is rare and associated with bacterial infection

• Antibodies to k antigen are seldom encountered

(KEL blood group) biochemistry of kell antigens

• Located on a glycoprotein that consists of 731 amino acids and spans the RBC membrane once

• Kell antigen expression dependent on the presence of the Xk protein

• Located on chromosome 7

(KEL blood group) Kx antigen

• Present on all RBCs except those with rare McLeod phenotype

• Expression of Kx increases with denaturing of Kell antigens by AET or DTT

(KEL blood group) K₀ phenotype + anti-Ku (K5)

lacks expression of all Kell antigens and produces anti-Ku(K5), causes HDFN and HTRs

(KEL blood group) McLeod phenotype + syndrome

• Rare phenotype with decreased Kell system antigen expression that ONLY AFFECTS MALES

  • Some males with this phenotype have the X-linked chronic granulomatous disease (CGD)

• Clinical Manifestations

  • Abnormal RBC morphology (acanthocytes)

  • Associated with hemolytic anemia

  • Neurological and muscular abnormalities

  • McLeod males with CGD make anti-Kx + Km (lack Kx and Km antigens)

  • McLeod males without CGD make anti-Km

(kell blood group) altered antigen expression + autoantibodies assoc w kell antigens

• Altered expressions of Kell antigens

  • Weaker than normal Kell antigen expression with McLeod phenotype

  • K_mod phenotype

• Autoantibodies associated with Kell antigens

  • Directed against undefined high prevalence Kell antigens

    • K, Kp^b, and K13

(general) duffy blood group system (FY)

• ISBT symbol FY, number 008, chromosome 1

  • 5 antigens—Fya and Fyb, Fy3, Fy5, and Fy6

• Most important antigens: Fy^a and Fy^b

  • Majority of AA population duffy null Fy(a-b-) (FY genotype)

  • FyFy common genotype in the AA population, especially in West Africa

  • Fy gene exceedingly rare in white population

• Disease association

  • Fy(a-b-) RBCs resist infection by Plasmodium knowlesi and vivax

(FY blood group) duffy antigen phenotypes

Fy^a and Fy^b are receptors for Plasmodium vivax and knowlesi, may offer protection against malaria

• Fy(a+b-) 17% Whites, 9% Blacks, 91% Chinese

• Fy(a+b+) 49% Whites, 1% Blacks, 9% Chinese

• Fy(a-b+) 34% Whites, 22% Blacks, 0.3 Chinese

• Fy(a-b-) very rare Whites, 68% Blacks, 0% Chinese

(FY blood group) expression + effect of enzyme treatment

• Well developed at birth

  • Detected on fetal RBCs as early as 6 weeks (gestation)

• Enzyme treatment

  • Destroyed by enzymes and ZZAP

(FY blood group) antibodies of concern (anti-Fya + Fyb)

• Usually IgG antibodies & react at the AHG phase (Anti-Fya > anti-Fyb)

• Rarely bind complement

• Do not react with enzyme treated RBCs

• Show dosage (RBCs react strongly with double dose)

• Both antibodies implicated in acute and delayed HTRs; associated with HDFN

 

(FY blood group) other antigens (Fy^x, Fy3, Fy5)

• Fy^x – does not produce an antigen but an inherited weak form of Fy^b

  • Individuals type as Fy(b-)

  • No anti-Fy^x

• Fy3

  • not destroyed by enzymes

  • Rare anti-Fy3 found in serum of Fy(a-b-) phenotype

• Fy5

  • appears to be an interaction between Rh complex and Fy glycoprotein

  • Fy5 not destroyed by enzymes

  • Fy(a-b-) and Rh_null do not produce Fy5 antigen

(general) kidd blood group system (JK)

• ISBT symbol JK, number 009, chromosome 18

  • Glycoprotein carrying antigens transports urea across RBC membrane

  • Three antigens

    • Jk^a, Jk^b, and high incidence antigen, Jk3 (Jka and Jkb one or the other present for Jk3)

  • Anti-Jka and anti-Jkb are NOTORIOUS for causing delayed HTRs

    • Titers go away very quickly

(kidd blood group) Jka + Jkb antigens

•  commonly found on the RBCs of most individuals

  • well developed at birth

  • Jka detected on fetal RBCs as early as 11 weeks (Jkb = 7 weeks)

• Not very immunogenic

• Rarely indicated in HDFN

• Enzyme/chemical treatment

  • Not denatured with routine blood bank enzymes (enhanced)

  • Not affected by DTT, AET, chloroquine, or glycine-acid EDTA

(kidd blood group system) phenotypes

• Jk(a+b-) 28% White, 57% Black, 23% Asian

• Jk(a+b+) 49% White, 34% Black, 50% Asian

• Jk(a-b+) 23% White, 9 Black, 27% Asian

• Jk(a-b-) rare in white and Black ppl; more common in Polynesians

kidd blood group system antibodies (anti-Jka/Jkb)

• Can be difficult to detect (weak) and often found in combination with other antibodies; Anti-Jka more common than anti-Jkb

• Typically, IgG and react at the AHG phase

• Bind complement + demonstrate dosage

• Reactivity enhanced with enzymes, LISS, and PeG

• Produced in response to foreign RBC exposure during pregnancy or transfusion

• Common cause of delayed HTRs

• Antibody tiers decline quickly in vivo

(kidd blood group system) Jk(a-b-)

aka Jk null phenotype

• most abundant among Polynesian population

• Delayed lysis of null RBCs in 2M urea (used to screen families for phenotype)

• No associated clinical abnormalities

(kidd blood group system) anti-Jk3 + autoantibodies

• Anti-Jk3

  • Associated with severe immediate and delayed HTRs, mild HDFN

• Autoantibodies

  • Associated with AIHA

(general) lutheran blood group system (LU)

• ISBT symbol LU, number 005

• LU gene located on chromosome 19

• Linkage exist between the LU and Se gene

  • First example of autosomal linkage described in humans

• Three genetic explanations for the Lu(a-b-) phenotype

  • Dominant type, recessive type, and recessive X linked inhibitor type

• Lu(a-b-) phenotype = rare

  • Only individuals with the recessive type Lu(a-b-) produce anti-Lu3

LU blood group system antigens

• 29 antigens in Lutheran system

• Lu^a and Lu^b (more common) produced by codominant alleles

• Poorly developed at birth

• Most individuals are Lu^b pos = low number of antigen sites

• Lu (a-b-) null phenotypes arises from genetic situations

• Enzyme treatment

  • Resistant to ficin, papain, glycine-acid EDTA

  • Destroyed by trypsin, alpha-chymotrypsin

 

(LU blood group antibodies) anti-Lu^a

• Naturally occurring IgM saline agglutinins

• React better at room temp (IS) than at 37°C

• Some capable of binding complement

• In vitro hemolysis not reported

• Often undetected bc most reagent RBCs are Lu^a neg

• Characterized by loose, mixed-field reactivity

• Rare and mild delayed HTRs

(LU blood group antibodies) anti-Lu^b

• Most are IgG – reactive at 37°C & AHG phase

• Produced in response to pregnancy or transfusions of foreign RBCs

• Shortens survival of transfused cells and may cause post-transfusion jaundice

• RARE DONOR BANK of Lu^b antigen negative units!

(LU blood group antibodies) anti-Lu3

• Rare antibody – reacts with all RBCs except for Lu(a-b-) RBCs

• Usually reacts at the AHG phase

• Antibody produced by individuals with recessive type Lu(a-b-)

effect of enzyme treatment for the common blood group antigens

• ehanced by papain, bromelian, ficin, trypsin: Kidd, Rh, Lewis, I, P

• destroyed by enzymes: Duffy, MN, Xg^a

• unaffected by treatment: K, U, Lutheran

list of antigens that show dosage

• Jk^a + Jk^b

• Fy^a + Fy^b

• C, c; E, e

• M, N, S, s