Blood Groups and Serologic Testing PDF

 Chapter 7 The Rh Blood Group System 151 Antigens Agglutinogen Rh Factor...

 Chapter 7 The Rh Blood Group System 151 Antigens Agglutinogen Rh Factor D Gene D Close Production Factor Rh0 Rh0 Linkage C / c Gene C/c Rh° gene Factor hr' hr' Pathway E / e Gene E/e Factor hr'' hr'' RBC Surface RBC Surface Figure 7–1. Fisher-Race concept of Rh (simplified). Each gene produces one Figure 7–2. Wiener’s agglutinogen theory. Antibody will recognize each factor product. within the agglutinogen. continue to use the letter d with Fisher-Race terminology as of the haplotype. Each factor is an antigen recognized by an a placeholder for D-negative individuals. antibody. The original Wiener nomenclature named the five According to the Fisher-Race theory, an individual inherits common Rh antigens as Rho, rh9, rh0, hr9, and hr0, but these a set of RH genes from each parent (i.e., one D or d, one C or terms are no longer used in favor of a modified form of c, and one E or e). The combination of genes inherited from Wiener notation. one parent is called a haplotype. For example, if one parent In the modified Wiener nomenclature, an agglutinogen is has the genes D, C, and e, then the haplotype is written as described by a letter and symbol assigned based on the fac- DCe. The pairing of maternal and paternal haplotypes deter- tors present. The uppercase R denotes the presence of the mines the offspring’s genotype (the RH genes inherited from D antigen. The lowercase r indicates the absence of D antigen. each parent). The genotype is written as two haplotypes sep- The presence of the C antigen is indicated by a 1 or a single arated by a / (i.e., DCe/Dce). There are rare phenotypes that prime (9). The c antigen is implied when there is no 1 or 9 involve deletions of specific genes, and in those cases the indicated. The E antigen is indicated by a 2 or double prime deletion is represented with a dash. For example an individ- (0) and the e antigen is implied when no 2 or 0 is indicated. ual having only D and no C/c and E/e, the Fisher-Race haplo- That is, R1 is the same as DCe; r′ denotes Ce; and Ro is equiv- type is written as D–. Placing parenthesis around (D), (C), alent to Dce. The presence of E is indicated by the Arabic and (e) indicates weakened antigen expression. Table 7-1 number 2 or double prime (0). Lowercase e is implied when compares serologic reactions to Fisher-Race nomenclature for there is no 2 or 0 indicated—that is, R2 is the same as DcE; r0 haplotypes. denotes cE, and r is equivalent to ce (again, it is assumed that a c antigen is present). When both C and E are present, the Wiener: Rh-Hr Terminology letter z or y is used. Rz denotes DCE, whereas ry represents CE. Phenotypes of less common Rh types such as Rhnull In his early work defining the Rh antigens, Wiener believed and Rhmod are written as stated. The genotype for the Rhnull there was one gene responsible for defining Rh that produced that arises from an amorphic gene at both Rh loci is written an agglutinogen containing three Rh factors5 (Fig. 7–2). The 5 and pronounced “little r double bar.” These will be as rr agglutinogen may be considered the phenotypic expression discussed later in this chapter. See Table 7–2 for a sum- mary of this shorthand nomenclature for the common agglutinogens. Table 7–1 Fisher-Race Haplotype Modified Wiener terminology allows one to convey Rh Terminology antigens inherited on one chromosome or haplotype and Designation makes it easier to discuss a genotype. Fisher-Race nomen- clature may be converted to Wiener nomenclature and vice Phenotype Reaction With Antisera versa. It is important to remember that an agglutinogen in D C E c e Wiener nomenclature actually represents the presence of a single haplotype expressing three different antigens. In the + + 0 0 + DCe Wiener nomenclature, there is no designation for the ab- 0 + 0 0 + Ce sence of D antigen. By using these designations, the labora- torian should be able to recognize immediately which + 0 + + 0 DcE antigens are present on the RBCs. 0 0 + + 0 cE Rosenfield and Coworkers: Alphanumeric + + + 0 0 DCE Terminology 0 + + 0 0 CE In the early 1960s, Rosenfield and associates proposed a sys- + 0 0 + + Dce tem that assigned a number to each antigen of the Rh system 0 0 0 + + ce in order of its discovery or recognized relationship to the Rh system.6 This system has no genetic basis, nor was it proposed 152 PART II Blood Groups and Serologic Testing Table 7–2 Wiener Haplotype Terminology Shorthand Symbol D C E c e Designation R 1 + + 0 0 + R1 r 9 0 + 0 0 + r9 R 2 + 0 + + 0 R2 r 0 0 0 + + 0 r0 R Z + + + 0 0 Rz r y 0 + + 0 0 ry R 0 + 0 0 + + R0 r 0 0 0 + + r based on a theory of Rh inheritance, but it simply demon- Table 7–3 Rh Genotypes by Three strates the presence or absence of the antigen on the RBC. Nomenclatures Each antigen is assigned a number. A minus sign preceding a number designates the absence of the antigen. If an antigen Wiener Fisher-Race Rosenfield has not been phenotyped, its number will not appear in the R 1r DCe/ce Rh:1, 2, –3, 4, 5 sequence. An advantage of this nomenclature is that the RBC phenotype is thus succinctly described. R 1R 1 DCe/DCe Rh:1, 2, –3, –4, 5 For the five major antigens, D is assigned Rh1, C is Rh2, R 1R 2 DCe/DcE Rh:1, 2, 3, 4, 5 E is Rh3, c is Rh4, and e is Rh5. For RBCs that type D- positive, C-positive, E-positive, c-negative, and e-negative, R 2r DcE/ce Rh:1, –2, 3, 4, 5 the Rosenfield designation is Rh: 1, 2, 3, –4, –5. If the sample R 2R 2 DcE/DcE Rh:1, –2, 3, 4, –5 was not tested for e, the designation would be Rh: 1, 2, 3, –4. The numeric system is well suited to electronic data process- R or Dce/ce Rh: 1,-2, -3, 4, 5 ing. Its use expedites data entry and retrieval. Its primary R oR o Dce/Dce Rh: 1,-2, -3, 4, 5 limiting factor is that there is a similar nomenclature for nu- merous other blood groups, such as Kell, Duffy, Kidd, and R zr DCE/ce Rh:1, 2, 3, 4, 5 more. Therefore, when using the Rosenfield nomenclature rr ce/ce Rh: –1, –2, –3, 4, 5 on the computer, one must use both the alpha (Rh:) and the numeric (1, 2, –3, etc.) to denote a phenotype. Table 7-3 lists r9r Ce/ce Rh: –1, 2, –3, 4, 5 common Rh genotypes comparing the nomenclatures of r9r9 Ce/Ce Rh: –1, 2, –3, –4, 5 Wiener, Fisher-Race, and Rosenfield. r0r cE/ce Rh: –1, –2, 3, 4, 5 International Society of Blood Transfusion r 0r 0 cE/cE Rh: –1, –2, 3, 4, –5 Committee: Updated Numeric Terminology r9r0 Ce/cE Rh: –1, 2, 3, 4, 5 As the world of blood transfusion began to cooperate and share data, it became apparent there was a need for a univer- (ryr) CE/ce Rh: -1, 2, 3, 4, 5 sal language. The International Society of Blood Transfusion (ISBT) formed the Committee on Terminology for Red Cell Surface Antigens. Its mandate was to establish a uniform unchanged but were converted to all uppercase letters (e.g., nomenclature that is both eye- and machine-readable and is Rh, Kell became RH, KELL). Therefore, D is RH1, C is RH2, in keeping with the genetic basis of blood groups.7 The ISBT and so forth. (Note: There is no space between the RH and adopted a six-digit number for each authenticated antigen the assigned number.) The phenotype designation includes belonging to a blood group system. The first three numbers the alphabetical symbol that denotes the blood group, represent the system, and the remaining three the antigenic followed by a colon and then the specificity numbers of the specificity. Number 004 was assigned to the Rh blood group antigens defined. A minus sign preceding the number in- system, and then each antigen assigned to the Rh system was dicates that the antigen was tested for but was not present. given a unique number to complete the six-digit computer The phenotype D + C – E + c + e + or DcE/ce or R2r would number. Table 7–4 provides a listing of these numbers. be written RH:1, –2, 3, 4, 5. When referring to individual antigens, an alphanumeric When referring to a gene, an allele, or a haplotype, the designation similar to the Rosenfield nomenclature may symbols are italicized. A haplotype is followed by a space or be used. The alphabetic names formerly used were left an asterisk, and the numbers of the specificities are separated  Chapter 7 The Rh Blood Group System 153 Table 7–4 Antigens of the Rh Blood Group System in Four Nomenclatures Rosenfield Fisher-Race Wiener ISBT Number Other Names or Comment Rh1 D Rh0 004001 Rh2 C rh9 004002 Rh3 E rh0 004003 Rh4 c hr9 004004 Rh5 e hr0 004005 Rh6 ce hr 004006 f Rh7 Ce rhi 004007 Rh8 Cw rhw1 004008 Rh9 Cx rhx 004009 Rh10 V hrv 004010 ceS Rh11 Ew rhw2 004011 Rh12 G rhG 004012 Rh17† Hr0 004017 Rh18 Hr 004018 HrS (high prevalence) Rh19 hrs 004019 Rh20 VS es 004020 Rh21 CG 004021 Rh22 CE Rh 004022 Jarvis Rh23 Dw 004023 Wiel Rh24† ET 004024 Rh26 c-like 004026 Deal Rh27 cE rhii 004027 Rh28 hrH 004028 Hernandez Rh29 004029 Total Rh Rh30 Dcor 004030 Goa (low prevalence) DIVa Rh31 hrB 004031 Rh32 RN 004032 Troll (low prevalence) Rh33 R0Har 004033 DHAR (low prevalence) Rh34 HrB 004034 Bastiaan Rh35 004035 (low prevalence) Rh36 004036 Bea (Berrens; low prevalence) Rh37 004037 Evans (low prevalence) Rh38† Formerly Duclos Rh39 C-like 004039 Rh40 Tar 004040 Targett (low prevalence) Continued 154 PART II Blood Groups and Serologic Testing Table 7–4 Antigens of the Rh Blood Group System in Four Nomenclatures—cont’d Rosenfield Fisher-Race Wiener ISBT Number Other Names or Comment Rh41 Ce-like 004041 Rh42 CeS , CceS rhis 004042 Thornton Rh43 004043 Crawford (low prevalence) Rh44 004044 Nou (high prevalence) Rh45 004045 Riv Rh46 004046 Sec (high prevalence) Rh47 “Allelic” to RN 004047 Dav (high prevalence) Rh48 004048 JAL (low prevalence) Rh49 004049 Stem Rh50 004050 FPTT (low prevalence) Rh51 004051 MAR (high prevalence) Rh52 004052 BARC (low prevalence) Rh53 004053 JAHK (low prevalence) Rh54 004054 DAK (low prevalence) Rh55 004055 LOCR (low prevalence) Rh56 004056 CENR (low prevalence) Rh57 004057 CEST (high prevalence) RH58 004058 CELO (high prevalence) RH59 004059 CEAG (high prevalence) RH60 004060 PARG (low prevalence) RH61 004061 CEVf by commas. The R1 haplotype or DCe would be RH 1,2,5 or Rhce, or RhCE proteins (Fig. 7–3). RHD and RHCE are RH*1,2,5. codominant, which means that all products inherited typi- cally produce antigens detectable on RBCs. RHD and RHCE Rh Nomenclatures Overview genes each have 10 exons and are 97% identical. Each gene has a number of alleles, most of which have been identified Tables 7–3, 7–4, and 7–5 summarize the data presented in through molecular testing techniques. this section. As the genetics and biochemistry of the Rh Numerous mutations have been described in the RH blood group system continue to be investigated, so too does genes. Greater than 250 alleles have been determined in the the terminology continue to change. For consistency of use, RHD gene, and 50 alleles have been found in the RHCE allele RHD and RHCE, all uppercase and in italics, will be used and the number continues to grow. A complete list of the from this point forward in the text to indicate genes. RhD, alleles found on the RHD and RHCE genes can be found on RhCe, RhcE, Rhce, and RhCE will be used to designate pro- the Rhesus-data base and the website for the National Center teins on which the Rh antigens reside. for Biotechnology Information (NCBI), which maintains a database for human blood group mutation.10,11 Fortunately Genetics for the medical laboratory scientist, many of these mutations are rare and do not change the serology observed in day-to- Rh Genes day testing. RHD and RHCE are two closely linked genes located on chro- Rh-Associated Glycoprotein (RHAG) mosome 1 that control expression of Rh proteins.8,9 The gene RHD codes for the presence or absence of the RhD protein, Another gene important to Rh antigen expression is RHAG, and the second gene RHCE codes for either RhCe, RhcE, and it resides on chromosome 6.12 The product of this gene  Chapter 7 The Rh Blood Group System 155 Table 7–5 Prevalence of the Principal Rh Haplotypes Fisher-Race Nomenclature Modified Wiener Nomenclature Prevalence (%) White African American Asian DCe R1 42 17 70 DcE R2 14 11 21 Dce Ro 4 44 3 DCE Rz