Transfusion Science 2

Rh Antibodies in vivo

Mostly IgG Ab ]→ enhanced in vitro by enzyme treated RBCs and with other potentiators - no complement activation (intravascular hemoloysis - extravascular hemolysis removes sensitized RBCs) *Clinical significance - transfusion reactions/HDFN

Rh Blood group Genetics

No allele to the D gene → locus RHD gene (presence of RhD protein) and locus for RHCE gene (RhCe/RhcE/Rhce/RhCE

Rh Blood Group System Nomenclature: Rosenfield vs. ISBT vs. Fisher-race vs. Wiener

Rosenfield: numbered antigen → serological PHENOTYPES - D=Rh1, C=Rh2, E=Rh3, c=Rh4, e=Rh5 (add a negative if missing) vs. ISBT: numeric genetics - Rh = 004, D = 001, C = 002… (Rosenfield for phenotype) vs. Fisher-Race: D for Rh+ and d/nothing for Rh- → C/E/c/e ]→ haplotype combinations vs. Wiener: shorthand notation - R = D and r = d, 0/nothing = ce, 1/’ = Ce, 2/” = cE, Z/y = CE

Common Haplotypes of Rh blood group system

R1r for Rh Positive vs. rr for Rh negative

D Antigen Strength

R2R2 has stronger reactions compared to R1R1 (C in cis to D)

Other Rh Antigen: Cw vs. f vs. G vs. Lw

Cw: Rh8 → Cc locus inherited - RhCE*Ce associated with R1 haplotypes ]- low frequency - anti-Cw natural occurrence and shows dosage (increase amount to increase strength) vs. f: Rh6 - compound Ag with ce in cis - Dce or dce → anti-f develops with negative c or e - receive either c- or e-negative blood (=f-negative) vs. G: Rh12 - D or C inherited code for G → anti-G mimics anti-D and anti-C (cannot separate activity of anti-G) - receive D- and C- RBCs vs. Lw: similar to Rh phenotype differ genetically → rhesus monkeys and human RBCs → anti-Lw reacts more strongly with D positive than D negative ]- clinical significance (rare)

Very Rare Unusual Phenotypes: Rh null vs. Rh mod vs. D-depletion vs. Partial Deleted

Rh null: No Rh on RBC due to amorphic (RHD absent → no RHCE expression ]- parents give one haplotype of Rh deletion each) OR regulatroy (gene inherited and normal but not expressed - RHAG missing for Rh Ag expression) vs. Rhmod: partial suppression of RH gene expression → RHAG mutations vs. D-Deletion: inherit RHD gene but nothing at RHCE locus → more D Ag than normal ]- transfuse only other D-deletion RBCs vs. Partial Deleted: inherit RHD gene with only part of RHCE locus → more D Ag than normal and reacts more strongly with anti-D ]- caused by inbreeding

Other Blood Group Systems: Kell vs. Duffy vs. Kidd

Kell: K <9% and immunogenic vs. k >99% (b = high frequency)]- codominant and antithetical → large protein with disulfide bonds - sulfhydryl sensitivity - destroys Kell Ag/dosage (stronger reactions with homozygous over heterozygous)/enzyme treated RBCs wont be reacted

Duffy: Fya and Fyb → codominant (born with the genes) → enzymes denature the genes ]- Malaria parasites use Duffy Ag as receptors (if negative for Duffy - they resist malaria) ]→ IgG/significant/37C/AHG/dosage/enzymes render the Ag nonreactive

Kidd: Jka and Jkb - dosage/weak/combine Ab/difficult to detect/common cause of hemolytic transfusion reactions (delayed)/enhanced reaction with enzyme