review for quiz 2

• Prevalence of Rh

  • caucasians of European descent: 15-17% are Rh-
  • 5% of Africa is Rh-
  • In the US: 15% is Rh-, while 85% is Rh+
  • Other common and significant Rh antigens are C, c, E, e
• Prevalence of Rh

  • there are actually more than 50 other Rh antigens, but not clinical significance
  • we only routinely test for presence of D
• Genes

  • the Rh proteins RhD and RhCE differ by 32-35 amino acids, so they are considered very different
  • Rh negative phenotypes are the result of the complete deletion of the RHD gene
• RHCE and RHD genes

  • RHCE encodes
  • C and c antigens, which differ by 4 amino acids
  • E and e which differ by one amino acid
• Fisher and Race

  • Fisher and Race believed that the Rh system consisted of three closely linked genes or alleles
  • D at one locus
  • C or c at the second
  • E or e at the third
  • Used the terminology DCE
  • This is most frequently used in written discussions of Rh
• Weiner Terminology

  • Weiner terminology is based on the belief that the Rh antigens were the product of a single gene coding for an "agglutinogen" composed of multiple blood factors
  • these were named: Rh0, rh', rh", hr', and hr"
  • The original version is obsolete
• Weiner Terminology - Rh positive

  • R = D
  • r = absent D
  • Rh-positive = used when D is present
  • Dce = R0
  • DCe = R1
  • DcE = R2
  • DCE = Rz
• Weiner Terminology - Rh negative

  • Rh-negative (d), no D
  • dCe = r'
  • dcE = r"
  • dCE = ry
  • dce = r
• Rosenfeld 1962

  • a numerical nomenclature gave each Rh antigen a number based on the order of its discovery
  • not in wide use
• Rosenfeld 1962

  D = Rh1
• Rosenfeld 1962

  C = Rh2
• Rosenfeld 1962

  E = Rh3
• Rosenfeld 1962

  c = Rh4
• Rosenfeld 1962

  e = Rh5
• Dce is not common among white/asian populations, but is common (44%) amongst black populations
• DCe is not very common in black populations, but is more common in white (42) and Asian (70) populations
• DcE is not common amongst any groups, but is most prevelent in Asian population (21)
• ce is most common amongst whites (37), then black (26) pop
• RHD and RHCE encode 417 amino acid proteins
• RHCE gene is found in all but rare cases, called D--
• Their antigenicity from highest to least: D>c>E>C>e
• Less D is expressed when the C antigen is present - this is called the Ceppellini Effect
• The D antigen is made of 30 or more epitopes
• D variants

  Weak D - a decrease in the amount of normal D
• D variants

  Weak D due to C - can occur when Ce is on the other allele
• D variants

  Partial D - lack of portions of the D antigen
• D variants

  Del - near complete absence of normal D
• D variants

  D el

  • will type as D-neg in the lab, even with IAT (indirect antiglobulin testing)
  • need to do an elution test
  • Found in 10-30% of Asians, will usually be found by molecular RHD genotyping
• • Weak D type 1 is most common in European ancestry
  • only about 1-2% of individuals with European ethnicity carry weak or partial D
• • Weak D is higher in African ethnicity
  • "Psi" - pseudogene-premature stop; there is no viable transcribed D antigen
• Weak D types 1, 2, and 3 make up about 90% of the weak D types, can be further weakened by Ceppellini effect
• Donor Blood and Weak D

  • AABB standards require donor blood at the site of collection to be weak D typed, if it is D-negative on the immediate spin
  • if it is positive after weak D testing, it must be labeled as "Rh positive"
  • Units that arrive at the positive labeled "Rh negative" must be retyped, but don't need to do weak D testing again
• C and c antigens

  • these are encoded by RHCE gene
  • it is codominant, so if you have genes for both you will have both antigens on the red cell surface
  • both antigens are less immunogenic than D
  • C: about 68% in whites; higher in eastern Asians; lower in African blacks
  • c: about 80% in whites
• Altered C and c Antigens

  • there are low frequency alterations:
  • Cw: (Rh8)
  • only one amino acid different from regular C
  • found in 1% of the US populations
• Altered C and c Antigens

  • there are low frequency alterations:
  • Cx (Rh9)
  • May see anti-C in these patients after a transfusion even though they type positive for C antigen
• E and e antigens

  • These are encoded by the RHCE gene
  • they are codominant
  • e is more frequent than E in all populations
  • E is more antigenic than e
  • alterations exist, but they are very rare
• Deleted/Partially deleted phenotypes

  • in rare cases, people inherit inactivated or partially active RHCE genes - they may not encode E or e; or C or C
  • This is found in whites whose parents are distant cousins
  • D antigen will be present, usually in decreased amounts
  • types described: D--, Dc-, DCw
• The G antigen

  • it is a product of 2 RHD genes or the product of 2 RHCE-Ce genes
  • Therefore, red cells that are D or C positive are also G positive
  • antibodies to G appear as anti-D and anti-C that cannot be separated
  • Biochemically, the expression of the G antigen depends on the presence of a common amino acid (serine) present on the surfac eof both D and C antigens
• Rh antibodies

  • Rh system is primarily red cell stimulated
  • either through transfusion or pregnancy, or even need sharing
  • most are IgG1 or IgG3 (some are IgM)
  • appear 6 weeks to 6 months after exposure
  • usually found after IAT, they react best at 37 degrees
  • antibodies usually do not bind complement ( they are probably too far apart on the RBC to bind C1q)
• Rh immune globulin

  • they figured this out from ABO incompatibilities that were not severe because moms naturally occurring antibodies wiped out babies' cells before IgG antibodies developed
  • it is given to Rh-negative moms who carry Rh-positive babies
  • Rh immune globulin is human IgG anti-D
  • in the US, it is administered at the 28thw eek of pregnancy and again after delivery of Rh-positive infant, or at the time of spontaneous or induced abortion
  • it only prevents anti-D HDFN