MIDTERM - RH GROUP

• Rh blood group system


  A red cell antigen with clinical importance because of its role in Hemolytic Disease of the Newborn and other hemolytic transfusion reactions
• Before 1939, the only significant blood group antigens were those of ABO groups
• Levine and Stetson discovered the first human Ab directed against the D Ag


  1939
• This was detected in the serum of a woman whose fetus had fatal Hemolytic Disease of the Newborn (HDN)
• Landsteiner and Wiener reported on an Ab made by guinea pigs and rabbits when they are transfused with rhesus monkey RBCs

  1940
• 85% human RBCs agglutinated: Rh positive
• 15% no agglutination: Rh negative
• Hemolytic Disease of the Fetus and the Newborn


  The condition wherein the mother is forming antibodies directed to the antigen present in the infants/neonates
• IgG


  Capable of crossing the placenta
• Anti-D


  Refers to D antigen present in red cell surface which is the basis whether an individual is Rh positive or Rh negative
• Immunologic reaction


  • Antibodies formed in women (anti-D or anti-Rh) are not identical with those formed by rabbits and guinea pigs (anti-LW)
• Rh Ag


  Non-glycosylated CHON in the red cell membrane inherited as autosomal dominant
• Rh locus


  Chromosome no. 1
• Nomenclature of the Rh System

  • Fisher-Race/DCE terminology
  • Wiener/Rh-Hr terminology
  • Rosenfield/Alpha-Numeric terminology
  • ISBT/Numeric terminology
• Two of the terminologies are based on the postulated genetic mechanisms of the Rh system
• The 3rd terminology describes only the presence or absence of a given antigen
• The 4th is the result of the effort of the International Society of Blood Transfusion (ISBT) Working Party on Terminology for Red cell Surface antigens
• Fisher-Race (DCE terminology)


  Investigated the antigens found on human red cells including the newly defined Rh antigen
• Fisher-Race proposal


  • Each person inherits a set of Rh genes from each parent (one D, or d, one C or c, and one E or e)
  • Rh genes are co-dominant, each inherited gene expresses its corresponding antigen on the red cell
• Phenotype


  Blood type observed during testing
• According to the Fisher-Race proposal, d doesn’t represent an antigen but simply the absence of the D antigen
• Rh genes


  • D
  • d
  • C
  • c
  • E
  • e
• Immunogenicity


  • D>c>E>C>e (most to least)
• Production pathway


  1. Antigens D

  2. C/c

  3. E/e
• Wiener (The Rh-Hr terminology)


  Believed that the gene responsible for defining Rh produced an agglutinogen that contained a series of blood factors
• Agglutinogen


  A substance that stimulates the production of an agglutinin, thereby acting as an antigen
• Fisher-Race nomenclature may be converted to Wiener nomenclature and vice versa
• Rosenfield (Alpha numeric terminology)


  Proposed a system that assigns a number to each antigen of Rh system in order of its discovery or recognized relationship to the Rh system
• A minus (-) sign preceding a number designates the absence of the Ag
• Rosenfield designation


  • Rh1: D
  • Rh2: C
  • Rh3: E
  • Rh4: c
  • Rh5: e
• All Rh system antigens have been assigned a number
• ISBT Numeric terminology


  Adapted a six-digit number for each blood group
• The first three numbers represent the system and the remaining three represent the antigenic specificity
• Weak D


  Variations of the Rh D Antigen Expression
• Weak D variations


  • C-trans
  • Partial D
  • Genetic weak D
• 1. trans


  Inheritance of the Ce (r’) gene in trans to the RHD gene
• Mosaic/Partial D/D variant


  Structure of D antigen is in mosaic structure, composed of 4 fragments
• 1. trans (Position effect)


  Inheritance of the Ce (r’) gene in trans to the RHD gene
• Inheritance of C in trans position to D weakens expression of the D antigen in red cells
• Dce/dCe


  • Trans position: steric arrangement interferes with D expression
  • DCe/dce: cis position