Ii and P blood Group

Question 1

Talk about the I and i antigens

Answer 1

They are both considered uncompleted ABH active chains

i is linear/non branched -> adds on last 2 sugars but in a straight line

All cord blood is i+ I-, i is gradually converted to I as we age

Question 2

What blood group has the most I antigen sites

Answer 2

Bombay -> no H antigen at all -> therefore lots of unfinished chains

Question 3

Talk about the genetics of the I/i system

Answer 3

I and i genes found on chromosome 6

Their products are transferase enzymes that attach repeating units of Gal and GlcNAc to the ABO Precursor substance

Big I gene encodes for branching of the polysaccharide

Question 4

Talk about the presence of i vs I, frequency etc

Answer 4

i gradually converted to I within the first 18 months of life

Not all is converted to I, some still prsent on adult cells

Question 5

Talk about anti-I

Answer 5

Its a common cold autoantibody

We used to use cord blood to identify these (i positive)

but we were unsure if cord blood was HIV negative so we switched over to adult little i to test cells in lab etc

Question 6

Where are the Ii antigens found?

Answer 6

Saliva
Human milk
On leukocytes
On platelets
In amniotic fluid
Urine

Question 7

How are I/i antigens affected by enzymes?

Answer 7

Enhanced by enzyme treatment

Question 8

When might you see i in adults?

Answer 8

i antigen persisting into adulthood without conversion to I is very rare

Question 9

Talk about anti-I antibody

Answer 9

Common autoantibody -> nearly everyone has a cold reactive anti-I -> but its IgM and only reactive at low temps so not clinically significant

It will react with virtually all adult red blood cells but not cord cells

Used to cause unwanted positivity in DAT in donor units

Question 10

Talk about anti-I DAT interference, how do we avoid this?

Answer 10

Nearly everyone has an anti-I antibody that reacts at cold temperatures

This doesnt cause any problems in patient but will cause complement binding when donor packs are refrigerated

We now use monospecific IgG AHG (wont pick up IgM anti-I) because of this

DAT+ unit -> then do IgG vs complement -> if complement only not concerned

Question 11

How do we investigate an alli anti-I, which are clinically significant

Answer 11

Can remove by pre-warming everything or reduce activity

Cold technique will enhance any weak reactions

If anti-I reacts at 30 degrees and titre is greater than 1000 then antibody is pathologic

Question 12

Talk about pathologic anti-I

Answer 12

Reactive at 30 degrees and titre > 1000

Wide thermal range of reactivity and high titre -> will react at 4 degrees and higher temps (30)

Good at complement binding

This is true cold agglutinins disease

Question 13

What causes pathologic anti-I

Answer 13

Cold agglutinin syndrome secondary to M. pneumoniae infectons

anti-i in IMS???

Question 14

What do we do with a pathoogic anti-I in the lab?

Answer 14

These will be pan reactive
Can mask clinically significant allo-antibodies
-> auto adsorption may be necessary to remove reactivity

Question 15

How do we carry out cold adsorption for investigation of anti-I

Answer 15

We use REST - rabbit erythrocyte stroma ___
-> lysed rabbit rbcs, conventraed stroma
-> cells covered in H and I antigens

Incubate patient plasma with these REST cells and then spin down

Take off plasma and test again

Auto-reactivity decreases with each cycle

Question 16

How do we carry out cold adsorption for investigation of anti-I

Answer 16

We use REST - rabbit erythrocyte stroma ___
-> lysed rabbit rbcs, conventraed stroma
-> cells covered in H and I antigens

Incubate patient plasma with these REST cells and then spin down

Take off plasma and test again

Auto-reactivity decreases with each cycle

Question 17

What is ati-IH, where is it found?

Answer 17

Found in the serum of A1 phenotype

These antibody will reacts strongly with RBCs high in H as well as I antigens

Reacts strongly with O cells

Question 18

Talk about anti-i

Answer 18

Fabian has never seen this

Antibody will react with cord cells

IgM antibody - reacts best at 4 degrees

Potent auto anti-i in children with IMS
- transient

Question 19

Talk about the history of the PIPK system

Answer 19

Landsteiner and levine discovered anti-P first in 1927

Question 20

What antigens are part of the PIPk system?

Answer 20

P1 and Pk

Question 21

Talk about the genetics of the PIPK system

Answer 21

Locus is on chromosome 22

Gene encodes enzymes that suquentially add sugars to precursor subatance -> related to ABO, Le and Ii systems

Question 22

What antigens are part of the GLOB system

Answer 22

P and p

• p is the amorph of P and was originally called Tj(a)

Question 23

Where is the GLOB locus

Answer 23

Chromosome 3

Question 24

Talk about the expression of PIPK and GLOB antigens

Answer 24

All antigens (P, Pk and P1) are expressed in glycosphingolipids on rbcs, not in glycoproteins

Antigens are built through the addition of sugars to precursor glycosphingolipids, analogous to A, B and H antigens

Question 25

Talk about expression of P1 antigens

Answer 25

P1 antigens are built y adding Gal in a alpha(1->4) linkage to the same precursor substance (paragloboside) as H, A, B, I and i antigens are built

Question 26

Where is P1 antigen found and why?

Answer 26

Only found on red cells as type 2 chains needed Millions of copies on red cell

Question 27

What is complicated about the genetics of PIPK and GLOB antigens

Answer 27

Chr 22 and 3 involved in formation of antigens Some overlap between these

Question 28

Talk about the frequency of P and p

Answer 28

Vast majority of people are P+ p similar to Bombay -> as your both blood group negative P and PIPK are separate blood group systems but both rely on similar base structure -> if p then equivalent to Bombay -> these produce an anti-PIPPK

Question 29

What are the enzymes resposible for P1, PK and P

Answer 29

P1 and Pk = alpha4GalT1 P = B3GalNAcT1

Question 30

What is the basic precursor structure for Pk, P1 and P

Answer 30

Cerimide = basic sugar on rbc Cetrimide + glucose GlcCer -> LacCer LC3 -> P1 OR LacCer -> Pk -> P

Question 31

Talk about P2

Answer 31

Theres no P2 antigen it is just a lack of P1 -> P2 individuals produce an anti-P1

Question 32

Talk about P2

Answer 32

Theres no P2 antigen it is just a lack of P1 -> P2 individuals produce an anti-P1

Question 33

If P2 individuals lack a P1 how can they still have a pK

Answer 33

This is due to splice variants in the alpha galatsoyl transferase enzyme -> P2 are not deficient in the enzyme they just have a modified version This splice variant favours making Pk and not P1 Splice variants are quite common but deficiency very rare

Question 34

Talk about the p phenotype

Answer 34

These lack P, P1 and Pk Called p phenotype These produce an anti-P, P1 and Pk

Question 35

Talk about anti-P1PkP

Answer 35

igG antibody Very strong Can cause HDFN Everything in panel comes up positive but auto negative Rare but IBTS got one last year

Question 36

Talk about the Pk phenotype

Answer 36

Only the second enzyme missing in chain i.e. still have Pk and P1 P- -> anti P1 produced

Question 37

PIPK Antigen frequencies in Caucasians

Answer 37

P1 = 79% P2 = 21% p = rare P1k = very rare P2k = most rare

Question 38

PIPK frequencies in Blacks

Answer 38

P1 = 94% P2 = 6% p = rare P1k = very rare P2k = most rare

Question 39

What are the general characteristics of the P1 antigen

Answer 39

Deteriorates durin storage - similar to dufy in that you might need to use fresh panel if query an anti-P1 Variable antigen expression between individuals -> often graded on antibody panels (1-5) Not well developed at birth -> no HDN

Question 40

Talk about anti-P1

Answer 40

Found in P2 phenotype Weak, cold reacting antibody IgM antibody that reacts best <25 Naturally ocuring Enhanced with enzymes Causes problems in reverse group or room temp crossmatch

Question 41

Talk about allo anti-P

Answer 41

Allo anti-P is naturally occuring in Pk phenotype (rare) Its clinically significant Can cause HDN and HTR Complement activation at 37 degrees

Question 42

Talk about auto anti-P

Answer 42

IgG found in PcH Called the Donath-Landsteiner antibody Biphasic haemolysin: binds complement at cold tem and activates complement in warm temo to lyse red blood cells Fouond in children <14 following viral infection and in tertiary syphilis

Question 43

Talk about auto anti-P

Answer 43

IgG found in PcH Called the Donath-Landsteiner antibody Biphasic haemolysin: binds complement at cold tem and activates complement in warm temo to lyse red blood cells Fouond in children <14 following viral infection and in tertiary syphilis