4. erythrocyte antigens & antibodies
Post on 18-Nov-2014
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• Discovered in 1900• On RBC’s, platelets &
endothelial cells• Considered also in solid
organ & BM transfusion• A, B & H Ag’s• A, B, AB, O phenotypes• Autosomal dominant –
A, B, AB• Autosomomal recessive
- O
ABO
MNSs
P
• 700 erythrocyte antigens
• 29 blood group systems by ISBT
• Usually high frequency and expressed by most donors (>90-99%)
• Some are private Ag’s• See Table 34-6 (JBH)
Intro1.Ag’s & Ab’s2.Ig class3.Serologic Phase of Det’n4.CS5.Stat
• ISBT 001• Ab’s against missing
antithetical Antigen• Null & weak phenotypes:–A2 (A1 are agglutinated by
Dolichos biflorus)–A2 may have anti-A1–Acquired B – bacteria or
Ca w/c deacetylates A Ag–Cis AB - single autosomal
allele for both A & B
ABO
MNSs
P
• Biochemistry:–CHO Ag’s, post
translation modification of glycoproteins & glycolipids–Type 2 oligosaccharide
precursor (repeating galactosaminyl motifs) & sphingolipids (type 1, 2, 3, 4)–FUT 1 (bld) & FUT 2
(sec) – alpha 1-2 H Ag
ABO
MNSs
P
• Biochemistry:–B Ag – alpha 1-3 Gal–A Ag – alpha 1-3 N-
acetylGal–Decreased Ag’s in
malignancy– Increased incidence of
diseases (autoimmune, neoplastic & infectious diseases)
ABO
MNSs
P
• Antibodies:–Naturally occuring
(IgM)–Absent 3-6 mts–Stable 5-10 yrs–Decreases with age–Anti-A,B is in grp O–RT saline 4 deg C– IgA & IgG – infrequent– IgG at 37, after stim–Can fix C’, HDN, HtR
ABO
MNSs
P
• Antibodies:–Rej’n of organs & BM
(due to delayed engraftment)–Anti-A1 in A2, A2B,
Ax, A3–Anti-H in A1 & A1B
non secretors, autoantibody usually, alloanti-H in Bombay & para
ABO
MNSs
P
• ISBT 002• 43 Ags• M/N & S/s – common• Only on RBC’s• Null phenotypes:–U – most common in
blacks–MkMk – lacks all–En (a-) – M-N- pheno
due to loss of glycophorin A
ABO
MNSs
P
• Antigens–Glycophorin A• 31 kDa• 131 aa• Type I glycoprotein• 72 a.a extracellular
domain• Transmembrane
domain• Major sialomucin on
RBC (zeta potential)• M & N reside here
ABO
MNSs
P
• Antigens–Glycophorin B• 20 kDa• 72 aa• extracellular N-
terminal domain• S/s & U reside here
ABO
MNSs
P
• Antibodies–Naturally occurring–RT saline– IgM–Anti M & N – show dosage–Destroyed by pre-
treatment of RBC’s with enzymes or neuraminidase
– Enhanced by pH 6.5 albumin, preincubation of RBC in a glucose sol’n
ABO
MNSs
P
• Antibodies–Anti M – common–Anti N – uncommon–Auto anti-N – dialysis
(due to formaldehyde neoantigen)
–Anti-S,s, U – always significant• IgG, 37, immune• May show dosage• U – unaffected by
enzymes• P. falciparum resistance
in glycophorin deficient En(a-)
ABO
MNSs
P
• ISBT 003 & 028• Pk, P, P1 – high
frequency, major Ag’s• Glycosphingolipids like
Lewis• RBC’s are rich in P Ag• Pk & P – also on WBC,
plasma, kidney, lungs, heart, placenta, uroepith, fibroblasts & synovium
• P1 on RBCs only
ABO
MNSs
P
QUIZ
1. ISBT No. of ABO2. ISBT No. of MNSs3. ISBT No. of P4. ISBT No. of Rh5. Autosomal recessive ABO
blood type6. High frequency P antigen7. Most common MNSs Ab8. Naturally/Immune: ABO9. Naturally/Immune: MNSs10.Naturally/Immune: Rh
Happy New Year!!!
QUIZ
11. ABO/MNSs/P: bombay12. ABO/MNSs/P:
formaldehyde neoantigen13. ABO/MNSs/P: glycophorins
A & B14. ABO/MNSs/P: weakened by
37 degrees incubation15. ABO/MNSs/P: Henshaw16. IgM/G/A/D/E: 80% of total
Ig in serum17. IgG1/G2/G3/G4: most
predominant18. IgG1/G2/G3/G4: most
efficient in complement fixation
Happy New Year!!!
ANSWERS
1. ISBT 001 ABO2. ISBT 002 MNSs3. ISBT 003 P4. ISBT 004 Rh5. Autosomal recessive ABO
blood type – TYPE O6. High frequency P antigen -
Pk/P/P17. Most common – anti-M 8. Naturally: ABO9. Naturally: MNSs10.Immune: Rh
Happy New Year!!!
ANSWERS
11. ABO: bombay12. MNSs: formaldehyde
neoantigen 13. MNSs: glycophorins A & B14. ABO: weakened by 37
degrees incubation15. MNSs: Henshaw16. IgG: 80% of total Ig in
serum17. IgG1: most predominant18. IgG3: most efficient in
complement fixation
Happy New Year!!!
• ISBT 004• Landsteiner & Wiener
immunized guinea pigs & rabbits with Rhesus monkey RBCs
• Antibody produced agglutinated 85% of human RBCs
• Similar to Levine & Stetson’s earlier studies
• Later proven to be Lw
Rh
Lutheran
Kell
Lewis
Duffy
• Most complex• 50 antigens• Wiener nomenclature (8
possible combinations of three-factor complexes
• Fisher-Race (genetic evidence of the antithetical or allelic nature of C/c or E/e Ags)
• Rosenfeld (numerical)• ISBT
Rh
Lutheran
Kell
Lewis
Duffy
• (3) integral membrane proteins – RHD, RHCE, RHAG
• Weak D Antigen–Former Du–1%–Causes: • Trans, two weak alleles • Partial D (RHD proteins
w/ missing D epitopes)
Rh
Lutheran
Kell
Lewis
Duffy
• Weak & Deletion C/c and E/e phenotypes
• Rh Null–Lack Fy5 and Lw–Markedly decreased
expression of S/s and U–Amorph & regulator
type–Stomatocytes &
spherocytes• Rh Mod
Rh
Lutheran
Kell
Lewis
Duffy
• Immune antibodies• IgG1 and IgG3 mostly• IgA and IgM also
known• Enhanced by enzyme
treatment, temp…• Immunogenecity of
Abs: D > c > E > C > e
• Anti-Cw and E can be naturally occurring
Rh
Lutheran
Kell
Lewis
Duffy
• Ubiquitously found on human tissues
• 18 antigens• ISBT 005• Antibodies are not CS• Mixed field: Anti-Lua
• Enzyme pre treatment• Null/weak phenotypes:–Autosomal recessive–Autosomal dominant–X-linked
Rh
Lutheran
Kell
Lewis
Duffy
• High affinity receptor for laminin
• Overexpression is hypothesized to play a role in metastasis of cancer (esp ovarian)
• Migration of erythrocytes
Rh
Lutheran
Kell
Lewis
Duffy
• Kell and Kx• ISBT 006 and 019• Racial differences• RBCs, erythroid and
megakaryocyte progenitors, skeletal muscle and testis
• KoKo – autosomal recessive, true null phenotype
Rh
Lutheran
Kell
Lewis
Duffy
• McLeod – antigens are depressed/absent
• X-linked recessive phenotype – XK protein is absent in RBCs, acanthocytes & neuromuscular disorders
• Transient depression of Kell antigens in septic & AIHA due to anti-Kell ab’s
Rh
Lutheran
Kell
Lewis
Duffy
• Clinically significant• HDN –
reticulocytopenia & little or no bilirubinemia
• Possible role in erythroid development
Rh
Lutheran
Kell
Lewis
Duffy
• Not of erythroid origin• Produced by GI and
passively absorbed by RBC
• Le(a_b_)• Naturally occurring• Important in disease
(H. pylori, Candidial vaginitis, heart disease)
Rh
Lutheran
Kell
Lewis
Duffy
• ISBT 008• Fya, Fyb – autosomal
codominant• Fy3, Fy5, Fy6 – high
incidence on all RBCs except Duffy null
• Fy4 – found to be unrelated
• Fyx – low expression of Fyb
Rh
Lutheran
Kell
Lewis
Duffy
• RBCs, purkinje’s cells, postcapillary venule & endothelial cells
• Clinically significant• IgG• Receptor for P. vivax
Rh
Lutheran
Kell
Lewis
Duffy
• ISBT 009• Jka and Jkb• Jk(a-b-) or null is rare
except in Polynesians and Finns
• In RBCs, descending vasa recta endothelial cells of renal medulla, heart, skeletal muscle, colon, SI, thymus, brain, pancreas, spleen, prostate, bladder, liver
Kidd
Diego
Cartwright
Xg
• Facilitates transport of urea
• Delayed HTR• IgG1 and IgG3 and
capable of activating complement
• Transient and disappear after stimulation
Kidd
Diego
Cartwright
Xg
• ISBT 010• RBCs and along the
collecting ducts• No racial differences
in expression• Immune, stimulated
or naturally occurring• Plays role in acid-
base equilibrium and gas transport
Kidd
Diego
Cartwright
Xg
• ISBT 011• On neural synapses
and neuromuscular junctions
• Clinically benign antibodies
• Associated with shortened red cell survival
Kidd
Diego
Cartwright
Xg
• ISBT 012• Single antigen Xga
• Two phenotypes• Mostly in men• HTR and HDN• Stimulated or
naturally occurring• IgG, can sometimes
fix complement
Kidd
Diego
Cartwright
Xg
• ISBT 013• Specific for RBCs and
erythropoietic tissues• ERMAP (in adhesion
and signaling) • Antibodies are rare
and usually benign• Usually IgG
Scianna
Dombrock
Colton
LW
• ISBT 014• RBCs, fetal liver,
spleen• Integrin-associated
adhesion & circulating NAD+
Scianna
Dombrock
Colton
LW
• ISBT 015• Coa and Cob
• Coa – high incidence antigen present on 99.7% of donors
• Rare Co (a-b-) null phenotype
Scianna
Dombrock
Colton
LW
• RBC’s, PCT, descending LOH, renal vasa recta endothelium, chroid plexus, ciliary body, microvessels, gall bladder, placenta, some epithelial cells
Scianna
Dombrock
Colton
LW
• Antibodies are clinically significant
• Associated with shortened RBC survival, HTR and HDN
• Usually IgG isotype• Immune antibodies• Enhanced by AHG,
protease treatment, can sometimes bind C’
Scianna
Dombrock
Colton
LW
• Null phenotypes can make anti-Co3 or Anti-Coa+b
• Antigens reside on aquaporins, therefore, null cells have residual water permeability
Scianna
Dombrock
Colton
LW
• Null phenotypes can make anti-Co3 or Anti-Coa+b
• Antigens reside on aquaporins, therefore, null cells have residual water permeability
Scianna
Dombrock
Colton
LW
• ISBT 016• Landsteiner-Wiener• LWa & LWb
• Antigen exp is dependent on Rh exp
• Role in adhesion during erythroid early dev’t
• Clinically benign Ab’s• Plasma origin,
absorbed on RBC’s
Scianna
Dombrock
Colton
LW
• ISBT 017• 10 antigens• Ch/Rg• Plasma origin, passively
absorbed onto RBCs• Do not cause HDN nor
HTR, however, anaphylaxis w/ plasma & plts.
• IgG isotype• Bacterial meningitis
susceptibility in C4 deficiency
Ch/RdGerbichCromerIndianOKRAPHJMHGIL
• ISBT 020• Glycoproteins are on
fetal RBCs, platelets, kidney & fetal liver
• Usu clinically significant
• Null/weak phenotypes–Yus (Ge -2,3,4)–Gerbich (Ge-2,-3,4)–Leach (Ge-2,-3,-4)
Ch/RdGerbichCromerIndianOKRAPHJMHGIL
• Biological role: cytoskeleton formation
• Delayed HTR• Severe HDN• Low RBC viability• IgM or IgG• Both immune &
naturally occurring• Resistant to enzymes
Ch/RdGerbichCromerIndianOKRAPHJMHGIL
• ISBT 021• Present on Decay
accelerating factor present on tissues & secretions–All hematopoietic
stem cells, vascular endothelium, GI & GU epithelium, brain & body fluids–Cord RBCs
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• May cause HTR & low RBC viability
• IgG isotype• Null phenotypes: rare
autosomal recessive–Suffer from GI
disorders
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• ISBT 022• Adult & cord RBCs,
neutrophils, B lymphocytes & dendritic cells
• Vary in strength between individuals: Knb, Mcb, Sla
• Antibodies are clinically insignificant
• HTLA (high titer, low avidity)
• Plays role in phagocytosis of Leishmenia, Legionella & Mycobacteria, P. falciparum
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• ISBT 023• Inb common in whites• Ina & AnWj only among
Indians & Arab populations
• Carried by CD44 on hematopoietic cells, epithelial cells & neural tissue (thus, adhesion of WBC)
• AnWj transiently depressed during pregnancy & AIHA
• In(Lu) is an ex of weak phenotype
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• ISBT 024• Single high frequency
antigen, Oka
• RBCs, WBCs, hematopoietic progenitors
• Anti-Oka is described only in Japan
• IgG immune isotype
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• ISBT 025• Single antigen RAPH
or MER2• Decreases in
expression with erythroid maturation
• IgG immune isotype• Does not cause HTR
or HDN
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• ISBT 026• John Milton Hagen• Single high incidence
antigen JMH• RBCs, lymphocytes,
activated macrophages, thymus, brain, respiratory epithelium, placenta, testes & spleen
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• Carried on CD108, a semaphorin (cell signaling) family glycoprotein
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• ISBT 029• GIL (100% in donors)• Associated with HTR• Not HDN• Causes +DAT• Resistant to
proteases, sialidases & DTT
• Transportation of urea & glycerol
Ch/RdGerbichCromerKnopsIndianOKRAPHJMHGIL
• ISBT 027• I and i • i (cord cells, precursor
of I)• 18 months of age, I
increases• Both are ubiquitously
found on glycoproteins & glycolipids of all cell types
I
• The iadult is a rare, autosomal recessive phenotype associated with congenital cataracts
• Elevated i Ag is also observed on cord RBCs, reticulocytes, PNH and HEMPAS
• IgM, low titered cold agglutinins, may cross react
I
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