1 / 25

Rh BLOOD GROUP SYSTEM

Rh BLOOD GROUP SYSTEM. AHLS 311. HISTORY. Ab in serum of mother of stillborn child; responsible for the death of fetus? (1939, Levine and Stetson) Rb-derived Ab to Rhesus monkey RBCs reacts with 85% of human subjects; same Ab as reported by Levine? (1940, Landsteiner and Weiner)

dustin-carlson
Download Presentation

Rh BLOOD GROUP SYSTEM

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Rh BLOOD GROUP SYSTEM AHLS 311

  2. HISTORY • Ab in serum of mother of stillborn child; responsible for the death of fetus? (1939, Levine and Stetson) • Rb-derived Ab to Rhesus monkey RBCs reacts with 85% of human subjects; same Ab as reported by Levine? (1940, Landsteiner and Weiner) • Erythroblastosis fetalis (HDN) linked with Anti-Rh (1941, Levine et al)

  3. NOMENCLATURE: 4 VERSIONS • Fisher Race • Suggested 3 sets of closely linked alleles (D and d, C and c, E and e) • Each gene (except d, which is an amorph) causes production of an Ag • Inherited from parents in linked fashion as haplotypes • See Tables 6-1 and 6-2

  4. NOMENCLATURE • Weiner • Multiple alleles at 1 complex locus • 1 locus encodes for production of an agglutinogen which has 3 factors (antigens or epitopes) • Abs can recognize single or multiple factors • See Table 6-3

  5. WEINER’S THEORY

  6. WEINER & FISHER-RACE TERMINOLOGY

  7. WEINER & FISHER-RACE TERMINOLOGY D = R 1 ( C) Z (both C & E ) 2 ( E ) 0 (neither C or E ) D c e D C E D C D c E d = r ‘( C) y (both C & E ) ‘’ ( E ) (neither C or E ) d c e d C E d C e d cE

  8. NOMENCLATURE • Rosenfield • No genetic assumptions made • Numerical system • If listed alone, the Ag is present (Rh:1 = D Ag) • If listed with a “-”, the Ag is not present (Rh:1, -2, 3 = DcE) • If not listed, the Ag status was not determined • Adapts well to computer entry

  9. COMMON Rh TYPES BY 3 NOMENCLATURES

  10. NOMENCLATURE • Internatl. Soc. of Blood Transfusion • 6 digit number for each Ag specificity • First 3 indicate the blood group, eg., 004 = Rh • Last 3 indicates the Ag specificity, eg., 004001 = D Ag of Rh system • For recording of phenotypes, the system adopts the Rosenfield approach

  11. Rh PHENOTYPING • Uses • Parentage testing • Predicting hemolytic disease of the newborn (HDN) • Confirmation of Rh Ab specificity • Locating compatible blood for recipients with Rh Abs • Protocol • Mix unknown RBCs with Rh antisera • Take tubes through phases (IS, heat/potentiator, AHG, CCC); record data • Use published frequencies and subject information to determine genotype

  12. GENOTYPE FREQUENCIES • Dce (R1) 0.42 • dce (r) 0.37 • DcE (R2) 0.14 • Dce (R0) 0.04 • dCe (r’) 0.02 • dce (r”) 0.01 • DCE (Rz) <0.01 • dCE(ry) <0.01 The probability of 2 frequencies appearing together = the product of those 2 frequencies. For example, DCe/dce occurs with a frequency of 0.42 X 0.37 or 0.155.

  13. Rh ANTIGENS • Nonglycosylated proteins (A,B,H are CHOs) • Transmembrane molecules • D and CE are epitopes of proteins with 417 Aas that traverse the membrane 12 X • DNA sequences of D and CE differ by only 44 base pairs; CE, Ce, cd and cE are even more similar to D • Integral part of RBC membrane (Rhnull people have mild hemolytic anemia) • Density of Rh Ags on RBCs varies by phenotype (see Table 6-7)

  14. MODEL OF Rh PROTEIN

  15. D ANTIGEN VARIATIONS • Weak D • Some cells require addition of AHG (IDAT) to demonstrate agglutination with Anti-D • 3 mechanisms causing weak D expression • Genetic - inheritance of D genes which result in lowered densities of D Ags on RBC membranes • C trans - position effect; the D gene is in trans to the C gene, eg., Dce/dCe (C and D Ag arrangement causes steric hindrance weakening D expression) • D mosaic - 1 or more parts of the D Ag is missing; may result in production of Anti-D • People with weak D are considered Rh+ and receive Rh+ blood (except mosaics)

  16. D ANTIGEN VARIATIONS • Enhanced D • When c and D are in double doses, eg., cDe/cDe, (C has limiting effect on expression of D) • D-- or D .. represent partial locus deletions; usually seen in consanguinous situations

  17. D TESTING • Anti-D reagents • Saline-based - Low protein (fewer false positives); long incubation times; cannot convert to weak D testing • Protein-based - Faster, increased frequency of false positives; requires use of Rh control tube, converts to weak D testing • Chemically modified - “Relaxed” form of Anti-D in low protein medium; few false positives; saline control performed; converts to weak D testing • Blends of mAbs

  18. D TESTING • Protocol • Add Anti-D to “D” tube; Rh control to “C” tube • Spin, read and record • If “D” is positive, cells are Rh positive • If “D” is negative, continue testing • Add 22% albumin and incubate for 20” at 37oC • Spin, read, and record • Wash 3 X in saline • Add AHG, spin, read, and record • If “D” is positive after heat/albumin or AHG  cells are weak D positive; if negative, cells are Rh negative; “C” should always be negative • Add check cells to neg. tubes; spin, read & record

  19. WEAK D Ag IN THE LAB • Differences from normal D expression • Quantitative (inherited weak D or position effects) • Qualitative (mosaic D; could produce Anti-D) • If cells are weak D, consider the person to be Rh + • Dwnot given to D negative recipients • D positives usually OK for Dw recipients • Dw mothers do not receive RhoGAM • Donors and expectant mothers should be tested for weak D; transfusion recipiencts +/- for weak D testing (Dw people may receive D negative blood)

  20. OTHER ALLELES AND ANTIGENS • Weak C (Cw) • Not allelic to C and c (C and Cw usually seen together) • 2% of whites; very rare in blacks • Anti-Cw may be naturally occurring and shows dosage • f (ce) • When c & e are in cis, eg., dce/DCe • Combination Ag • Anti-f may be helpful in phenotyping

  21. OTHER ALLELES AND ANTIGENS • Ce • When C and e in cis • Compound Ag • Ab helpful in phenotyping • G • Always found with C-positive RBCs; usually with D-positive cells • Anti G appears to bind to D, C, and G • Many others

  22. ALLELIC DELETIONS • No Cc and/or Ee epitopes • DC-, Dc-, D-E, D-- • Enhanced or exalted D Ag expression • Rhnull (no Rh Ag expression at all) • ---/--- (double bar rr) • Or, because of independently inherited suppressor genes • If exposed to any Rh Ags, make Abs to those and to Rh 29 (“pan” or “total” Rh) • Causes a mild hemolytic anemia • Rhmod - weakened expression of all Rh Ags

  23. Rh ANTIBODIES • Immune IgG Abs (IgG1 and IgG3 most important) • React optimally at 37oC or with AHG • Order of immunogenicity: D > c > E > C > e • Do not bind complement (RBC destruction by Rh Abs is extravascular)

  24. Rh Abs: CLINICAL SIGNIFICANCE • Severe HDN • Severe transfusion reactions

More Related