MLSP 5513: Other Blood Groups Part 2

P system contains

P1 and Pk antigens

-encoded by the A4GALT gene

Globoside system (028) contains

only the P antigen

-encoded by the B3GALT1 gene

Globoside collection (209) contains

LKE antigens

P system characteristics

-biochemically related to ABH

-formed by glycosyltransferase enzymes

-antigen expression originates from 2 independent genes

Type 2 precursor chain is substrate for

P1 antigen

-not in secretions

P1 and P2 phenotypes are analogous to

A1 and A2 phenotypes

P1 phenotype: antigens & antibodies

P1, P, Pk

-no antibodies

- 79% white 94% black

P2 phenotype: antigens & antibodies

P, Pk

-anti-P1

-21% white 6% black

Tja phenotype: antigens & antibodies

no antigens

-anti- P, P1, Pk

P1 antigen characteristics

-poorly developed at birth

-fully developed by 6

-adults have variable antigen expression

-expressed stronger in blacks

-antigen deteriorates rapidly

Which gene inhibits expression of P1

In(Lu)

P1 antibodies are neutralized by

hydatid cyst fluid, pigeon/turtle dove droppings

Anti-P1 characteristics

-common in P2 people

-usually weak, cold agglutinin, IgM, naturally occurring

-reactivity enhanced with enzymes

Anti-Tja characteristics

-reacts with P, P1, Pk positive cells

-naturally occurring in all Tja people early in life

-Both IgM and IgG

What makes anti-Tja clinically significant

-reacts with all other RBC except other Pnull

-wide thermal range

-potent hemolysin (binds complement)

-can cause severe HTR and HDFN

-associated with spontaneous abortion

Alloanti-P characteristics

-naturally occurring in all Pk people

-reacts with all red cells except Pnull and Pk positive cells

-wide thermal range

-potent hemolysin binding complement

-transfusion reactions and HDFN

Autoanti-P characteristics

-paroxysmal cold hemoglobinuria

-cold reactive IgG autoantibody

-Bi-phasic antibody

Autoanti-P: Bi-phasic antibody

-binds to RBC in the cold

-complement is activated

-Red cells hemolyze when warmed to 37C

-use Donath-Landsteiner test to ID

Autoanti-Pk characteristics

-rare

-P1 people with biliary cirrhosis or autoimmune hemolytic anemia

-neutralized with hydatid cyst fluid

Luke antigen and antibody

-independent of P system

-only 5 alloantibodies found

-saline agglutinin

-clinically insignificant

Disease associations of P blood group

-P antigens associated with UTI

-P antigen is receptor for human parvovirus

-anti-PP1Pk and anti-P with early abortions

-autoanti-P with PCH following viral infection

I system: genetics

-I and i are not alleles

-just one allele = I

-i antigen remained in the li collection

What is the gene responsible for expression of the I antigen

GCNT2

-production of a glycosyltransferase

I glycosyltransferase modifies

the type 2 precursor chain found on the red cell surface

The i antigen consists of

a linear chain of sugars

Th expression of I and i antigens are

variable but inversely proportional to each other

Cord and neonatal RBCs express

only i

During the first 18 months of life, what happens to the i antigen

i decreases while I increases

Benign autoanti-I

-common in healthy people

-natural and benign cold antibody

-IgM

-reactively enhanced with enzymes

-compound antibody with anti-IH

Pathogenic autoanti-I

-potent IgM

-higher titers

-broad thermal range

-may be produced by microorganisms with I-like antigens

Alloanti-I

-IgG or IgM

-naturally occurring in i individuals

-clinically insignificant unless reactive at 37C

Autoanti-i

-IgM, cold reactive

-associated with EBV, myeloid leukemia, and alcoholic cirrhosis

-IgG forms can cause HDFN

Anti-It

-recognizes the I antigen in transition from i to I

-associated with Hodgkins lymphoma

KEL gene

-chromosome 7

-encodes a glycoprotein with enzymatic activity

Kell protein is covalently linked to

Kx protein via disulfide bond

Which Kell system antigen is very immunogenic

K antigen

K: frequency

low frequency

-easy to find compatible donors

k: frequency

high frequency

-hard to find compatible donors

Kpa: frequency

low frequency

Kpb: frequency

high frequency

Jsa: frequency

low frequency

Jsb: frequency

high frequency

K-k+ race stats

-91% white

-96.5% black

Kp(a-b+) race stats

-97.7% white

-100% black

Js(a-b+) race states

-100% white

-80% black

Kell system antigens characteristics

-on the surface of RBCs and testicular cells

-developed at birth

-not affected by enzymes to enhance/destroy agglutination

-denatured by DTT

Kp antigens include

Kpa, Kpb, Kpc

Which of the Kp antigens are low frequency alleles

Kpa and Kpc

Which of the Kp antigens are high frequency alleles

Kpb

Inheritance of the Kpa allele results in

decreased expression of Jsb, k and other Kell system antigens if present on the same chromosome

Kpc has a high frequency in what population

japanese population

Which J antigen has a low frequency

Jsa

Which J antigen has a high frequency

Jsb

Anti-K

-3rd most common antibody

-IgG

-rare IgM forms with bacterial infections

-formed after pregnancy or transfusion

-may bind complement

-high titers

Anti-K serological activity is decreased with

disulfide reducers

Anti-K is stronger with

PEG

Is Anti-K clinically significant

yes

associated with HTR and HDFN

How common are antibodies to Kpa and Jsa

uncommon

-often not on screening cells

Antibodies to Kpa and Jsa

-clinical similar to anti-K

-may be naturally occurring but most are acquired

-HDFN usually milder

How common are antibodies to high frequency antigens (k, Kpb, Jsb)

-rare

-easy to detect

-difficult to ID

Antibodies to k, Kpb, and Jsb

-clinical significance similar to anti-K

-HDFN mild

-compatible donors difficult to find

-use autologous blood

Autologous blood

-blood donation from family members

-individual who is registered as a rare donor

K (null) phenotype

-results by mutations in the Kel gene

-rare

-no RBC abnormality

If two mutated copies of the KEL gene are inherited, what happens

no Kell antigens are expressed on the cell surface

If K(null) phenotype is immunized, what could happen

-make anti-Ku

-can cause HDFN and HTR

How can you make K null cells

treating them with disulfide reducers

The antigens of the Kx system is controlled by

XK gene

-X chromosome

Kx antigens are found on

all normal cells

-linked to Kell system proteins

McLeod Phenotype (Kx negative)

-rare X-linked recessive

-XK gene mutaiton

-poor to no expression of Kell antigens

-acanthocytes

-decreased deformability of RBC

-chronic anemia

Mcleod syndrome

-muscle wasting, cardiomyopathy, psychiatric disorders

-elevated creatine phosphokinase

-premature death

Chronic granulomatous disease

-60% of mutations are X-linked

-No NADH-oxidase made by phagocytes

-severe susceptibility to infection

-formation of granulomas

-deletion of part of X chromosome (contains genes for CGD and McLeod syndrome)