Ii and P blood Group Flashcards
Talk about the I and i antigens
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
What blood group has the most I antigen sites
Bombay -> no H antigen at all -> therefore lots of unfinished chains
Talk about the genetics of the I/i system
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
Talk about the presence of i vs I, frequency etc
i gradually converted to I within the first 18 months of life
Not all is converted to I, some still prsent on adult cells
Talk about anti-I
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
Where are the Ii antigens found?
Saliva
Human milk
On leukocytes
On platelets
In amniotic fluid
Urine
How are I/i antigens affected by enzymes?
Enhanced by enzyme treatment
When might you see i in adults?
i antigen persisting into adulthood without conversion to I is very rare
Talk about anti-I antibody
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
Talk about anti-I DAT interference, how do we avoid this?
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
How do we investigate an alli anti-I, which are clinically significant
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
Talk about pathologic anti-I
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
What causes pathologic anti-I
Cold agglutinin syndrome secondary to M. pneumoniae infectons
anti-i in IMS???
What do we do with a pathoogic anti-I in the lab?
These will be pan reactive
Can mask clinically significant allo-antibodies
-> auto adsorption may be necessary to remove reactivity
How do we carry out cold adsorption for investigation of anti-I
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
How do we carry out cold adsorption for investigation of anti-I
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
What is ati-IH, where is it found?
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
Talk about anti-i
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
Talk about the history of the PIPK system
Landsteiner and levine discovered anti-P first in 1927
What antigens are part of the PIPk system?
P1 and Pk
Talk about the genetics of the PIPK system
Locus is on chromosome 22
Gene encodes enzymes that suquentially add sugars to precursor subatance -> related to ABO, Le and Ii systems
What antigens are part of the GLOB system
P and p
- p is the amorph of P and was originally called Tj(a)
Where is the GLOB locus
Chromosome 3
Talk about the expression of PIPK and GLOB antigens
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
Talk about expression of P1 antigens
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
Where is P1 antigen found and why?
Only found on red cells as type 2 chains needed
Millions of copies on red cell
What is complicated about the genetics of PIPK and GLOB antigens
Chr 22 and 3 involved in formation of antigens
Some overlap between these
Talk about the frequency of P and p
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
What are the enzymes resposible for P1, PK and P
P1 and Pk = alpha4GalT1
P = B3GalNAcT1
What is the basic precursor structure for Pk, P1 and P
Cerimide = basic sugar on rbc
Cetrimide + glucose
GlcCer -> LacCer
LC3 -> P1
OR
LacCer -> Pk -> P
Talk about P2
Theres no P2 antigen it is just a lack of P1
-> P2 individuals produce an anti-P1
Talk about P2
Theres no P2 antigen it is just a lack of P1
-> P2 individuals produce an anti-P1
If P2 individuals lack a P1 how can they still have a pK
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
Talk about the p phenotype
These lack P, P1 and Pk
Called p phenotype
These produce an anti-P, P1 and Pk
Talk about anti-P1PkP
igG antibody
Very strong
Can cause HDFN
Everything in panel comes up positive but auto negative
Rare but IBTS got one last year
Talk about the Pk phenotype
Only the second enzyme missing in chain i.e. still have Pk and P1
P-
-> anti P1 produced
PIPK Antigen frequencies in Caucasians
P1 = 79%
P2 = 21%
p = rare
P1k = very rare
P2k = most rare
PIPK frequencies in Blacks
P1 = 94%
P2 = 6%
p = rare
P1k = very rare
P2k = most rare
What are the general characteristics of the P1 antigen
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
Talk about anti-P1
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
Talk about allo anti-P
Allo anti-P is naturally occuring in Pk phenotype (rare)
Its clinically significant
Can cause HDN and HTR
Complement activation at 37 degrees
Talk about auto anti-P
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
Talk about auto anti-P
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
