Rh BLOOD GROUP SYSTEM

History

In 1939, Hemolytic Disease of the Newborn was first described by Levine and Stetson. The cause of hemolytic disease of the cause was not specifically identified but maternal antibody suspected. A year later 1940 Karl Landsteiner and Alexander Wiener injected animals with Rhesus monkey cells to produce an antibody which reacted with 85% of human red cells, which they named anti-Rh. 

Within a year Levine made connection between maternal antibody causing HDN and anti-Rh. Between 1943-1945 the other common antigens of the Rh system were identified. For many years the exact inheritance of the Rh factor were debated Weiner promoting ‘Rh’ and ‘hr’ terminology and Fisher-Race utilizing DCcEe for the various Rh antigens. In 1993, Tippett discovered true mode of Rh inheritance using molecular diagnostics.

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RhD antigen

The Rh (Rhesus) blood group system is clinically the most important blood group system after ABO. The Rh blood group system currently consist of 50 defined blood group antigens, among which the 5 antigens (alleles) D, C, c, E and e the most important one. The most commonly-used terms Rh factor, Rh positive, and Rh negative refer to the D antigen only.

The status is usually indicated by Rh positive (Rh+, does have the D antigen) or Rh negative (Rh-, does not have the D antigen) suffix to the ABO blood type. 

Rh positive means that D antigen is detected on the red cell surface. The status is usually indicated by Rh positive (Rh+, does have the D antigen) or Rh negative (Rh-, does not have the D antigen) suffix to the ABO blood type.

D is the most important antigen after A and B, but those lacks D antigen do not have natural alloanti-D. D antigen is highly immunogenic. It is because  majority of RhD negative person transfused with RhD positive blood would develop anti-D.

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5 Principle Antigens That May Be Found in Most Individual

üD found in 85% of the population

üC found in 70% of the population

üE  found in 30% of the population

üc found in 80% of the population

üe found in 98% of the population

ü(d) which has never been identified but refers to the 15% of the population who has no D antigen.

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Nomenclature of Rh System

Fisher – Race : DCE terminology

           Presence of 3 separate genes D, C and E and their alleles c and e and the absence of D since an anti–d has never been found. It closely linked on the same chromosome and are inherited as a group of 3. For example : CDe.

Rh Nomenclature using Fisher-Race Terminology

D positiWiener : Rh–Hr  terminology

One gene complex with a number of alleles resulting in the presence of various Rh antigens.  It consist of 8 alleles R0,  R1, R2, Rz, r, r’, r”, ry.ve

Rosenfield and coworkers : Alpha/Numeric terminology

In, 1960 Rosenfield proposed a system that assigns a number to each Rh antigen. This system has no genetic basis but simply demonstrates the presence or absence of the antigens on the red cells. A minus sign preceding a number designates absence of antigen.

D = Rh1, C = Rh2, E = Rh3, c = – 4 , e = –5  

ISBT : Numeric terminology

International Society of Blood Transfusion use numeric terminology to classify the Rhesus.  They adapted a six digit number  for each blood group. The first three number represent the system and the  remaining three represent the antigenic  specific.

Example: D – 004001 (004 – sy tem, 001 – antigenic specificity) 

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Variation of Rh Gene Expression

        When Rh–positive red cell are type for D antigen, they are expected to react strongly with anti–D reagent. During antiglobulin test if the result show D negative antigen after immediate spin, it must be proceed with indirect antiglobulin test. It used to know whether the individual inherit weak expression of the D antigen or the individual is negative D–antigen. A weak expression of the D antigen was referred to as (Du) .

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Weak D caused by:

Inherit genetic weak D

Individual inherit D gene that code for weakened D antigen.

Frequently happen among blacks population.

Steric hindrance

Position effect gene interaction. 

When allele carrying D is in trans position (opposite chromosome) towards allele carrying C gene.

Refer to mosaic model

D antigen is thought to be a mosaic model that consist of several individual part or epitope. 

Weak D typing due to one or more parts is missing. Typing serum designed to react with all part. 

When have missing parts results of weak reaction. 

Weak recipient of a normal D blood transfusion could potentially make an antibody to the part of they 

lack.

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Adverse effects

         The Rh antigen pose a danger for the Rh-negative person, who lacks the antigen, if the Rh-positive blood is given in transfusion. Adverse effects may not occur the first time Rh-incompatible blood is given, but the immune system responds to the foreign Rh antigen by producing anti Rh-antibodies. If Rh-positive blood is given again after the antibodies form, they will attack the foreign red blood cells, causing them to clump together, or agglutinate. The resulting hemolysis, or destruction of the red blood cell, causing serious illness and sometimes death.

       A similar hazard exist during pregnancy for the Rh-positive offspring of Rh-incompatible parents, when the mother is Rh-negative and the father is Rh-positive. The first child of such parents is usually in no danger unless the mother has acquired anti Rh-antibodies by virtue of incompatible blood transfusion. During labour, however, a small amount of the fetus’s blood may enter the mother bloodstream. The mother will then produce anti-Rh antibodies, will attack any Rh-incompatible fetus in subsequence pregnancies.

Rh positive offspring with Rh negative mother

     This process produces erythroblastosis fetalis, or hemolytic diseases of the newborn, which can be fatal to the fetus or to the infant shortly after birth. Treatment of erythroblastosis fetalis usually entails one or more exchange transfusions. The disease can be avoided by  vaccinating the mother with Rh immunoglobulin after delivery of her firstborn if there is Rh incompatibility. The Rh vaccine destroy any fetal blood cells before the mother’s immune system can develop antibodies.

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