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Lecture 4 bb The Rhesus (Rh) Blood Group system By Dr. Dalia Galal Hamouda The Rh(D) Antigen Rh is the most complex system, with over 45 antigens. The complexity of the Rh blood group Ags is due to the highly polymorphic genes that encode them. Discovered in 1940 after work on Rhesus monkeys. The 2nd most important after ABO in the cross-match test. Rh Genetics The genes that control the system are autosomal codominant located on the short arm of chromosome 1. The RhD gene encoding the D antigen is the most important which is a large protein on the red blood cell membrane Rh Antigen Frequency D antigen – 85% d antigen – 15% C antigen – 70% c antigen – 80% E antigen – 30% e antigen – 98% Rh Positive Rh Negative The presence or absence of D Ag determines if the person is Rh+ or Rh- Rh antigens are highly immunogenic, the D antigen is most potent D c E C e Highly Rarely Immunogenic Exposure to less than 1 ml of Rh positive red cells can stimulate Ab production in an Rh negative person. Nomenclature of the RH system 3 Different nomenclatures: 1- Fisher-Race 2- Weiner 3- Rosenfield Nomenclature 1- Fisher-Race Theory Rh inheritance is controlled by 3 closely linked loci on each chromosome.(crossing over does NOT occur) and the 3 genes on one chromosome are always inherited together Each locus has its own set of alleles which are: Dd , Cc , and Ee . The D gene is dominant to the d gene, but Cc and Ee are co-dominant. Fisher-Race Example: DCe/DCe individual is homozygous for D, C, and e genes DCe/dcE individual is heterozygous for D, C, e, d, c, and E genes 2- Wiener Theory There is one Rh locus at which occurs one Rh gene, but this gene has multiple alleles. For example, one gene R1 produces one agglutinogen (antigen) Rh1 which is composed of three "factors" The three factors are analogous to C, D, and e respectively The main difference between the Fisher-Race and Wiener theories is that the: – – Fisher-Race theory has three closely linked loci, the Wiener theory has only one gene locus at which multiple alleles occur. 3- Rosenfield Nomenclature Each antigen assigned a number Rh 1 = D Rh 2 = C Rh 3 = E Rh 4 = c Rh 5 = e In writing the phenotype, the prefix “Rh” is followed by colon, then number (if negative, number is preceded by -) Example: D+, C+, E-, c+, e+ is written as Rh:1,2,-3,4,5 Significance of Rh system After ABO, the Rh system is the second most important system. This is because: The D antigen is extremely immunogenic (activate the antibody production). It causes the production of anti-D in 50 - 70% of Rh(D) negative people who are exposed to the D antigen. Anti-D is the most common cause of severe hemolytic disease of newborn (HDN) and can cause in Utero death. Because of this, in blood transfusion, the patient and donor must be matched for Rh(D) type as well as ABO groups. The C and E Ags are not as immunogenic as D, routine typing for these Ags is not performed Rh antibodies Result from the exposure to Rh antigens IgG form Bind at 37°C and form agglutination Clinical important of Rh antibodies • • • • Related to Hemolytic and transfusion reactions Re-exposure to antigen cause rapid secondary response If any donor blood sample that types Rho(D) negative by either slide or rapid method must be tested further by indirect anti-globulin test (IDAT). If both test results are negative, the donor sample is considered Rh negative Hemolytic disease of the Newborn (HDN) Usually related to D antigen exposure and the formation of anti-D Usually results from D negative female and D positive male. – The baby will probably be D positive. 1st pregnancy not effected, the 2nd pregnancy and on will be effected-results in still birth, severe jaundice, anemia related to HDN. To prevent this occurrence the female is administered RHimmunoglobulin (IG). Rh factor Rh factor can cause complications in some pregnancies. Mother is exposed to Rh antigens at the birth of her Rh+ baby. First pregnancy Placenta Rh+ antigens Mother makes anti-Rh+ antibodies. Anti-Rh+ antibodies During the mother’s next pregnancy, Rh antibodies can cross the placenta and endanger the fetus. Possible subsequent pregnancies Weak D Phenotype Most D positive rbc’s react macroscopically with Reagent anti-D at immediate spin – – These patients are referred to as Rh positive Reacting from 1+ to 3+ or greater HOWEVER, some D-positive rbc’s DO NOT react (do NOT agglutinate) at Immediate Spin using Reagent Anti-D. These require further testing (37oC and/or AHG) to determine the D status of the patient.