Antigen-fact-book

Rh blood group system epE1 Cat EI Cat EII Cat EIII Cat EIV epE2 epE3 ϩ ϩ ϩ ϩ epE4 ϩ 0 0 ϩ 0 0 ϩ ϩ 0 ϩ ϩ ϩ Many examples of anti-E appear to be naturally-occurring. Anti-E is often present in sera containing anti-c. Not found on RBCs from non-human primates. References 1 Cartron, J.-P. (1994) Blood Rev. 8, 199–212. 2 Noizat-Pirenne, F. et al. (1998) Br. J. Haematol. 103, 429–436. 3 Kashiwase, K. et al. (2001) Transfusion 41, 1408–1412. c ANTIGEN Terminology Rh4 (004.004) hrЈ ISBT symbol (number) Briefly reported in 1941 when it was recog- Other names nized that, in addition to D, the Rh system History had four other common antigens; named when the antithetical relationship to C was Occurrence recognized Caucasians 80% Blacks 96% [97–98% if d(C)ceS (rЈS) phenotype Asians included] 47% Antithetical antigen Expressed C (RH2) See system pages for unusual Rh complexes Expression Cord RBCs Altered 135

Rh blood group system Molecular basis associated with c antigen1,2 Amino acid Pro 103 (and Pro 1023) on Rhce and RhcE protein are critical but requirements for expression of c antigen are not fully understood. RhD with a substitution of Ser103Pro expresses a weak c antigen. Effect of enzymes/chemicals on c antigen on intact RBCs Ficin/papain Resistant (↑↑) Trypsin Resistant (↑) ␣-Chymotrypsin Resistant (↑) Pronase Resistant (↑↑) Sialidase Resistant DTT 200 mM Resistant Acid Resistant In vitro characteristics of alloanti-c Immunoglobulin class Most IgG, some IgM Optimal technique IAT; enzymes Complement binding No Clinical significance of alloanti-c Transfusion reaction Mild to severe/immediate or delayed/ HDN hemoglobulinuria Mild to severe Autoanti-c Yes, may be mimicking alloantibody. Comments Expressed on RBCs from apes. References 1 Faas, B.H.W. et al. (2001) Transfusion 41, 1136–1142. 2 Cartron, J.-P. (1994) Blood Rev. 8, 199–212. 3 Westhoff, C.M. et al. (2000) Transfusion 40, 321–324. 136

Rh blood group system e ANTIGEN Rh5 (004.005) hrЉ Terminology Named in 1945 when its antithetical rela- tionship to E was recognized. ISBT symbol (number) Other names History Occurrence 98% 98% Caucasians 96% Blacks Asians Antithetical antigen E (RH3) Expression Expressed See system pages for unusual Rh complexes Cord RBCs See table for reactions of monoclonal anti-e Altered with unusual Rh complexes Molecular basis associated with e antigen1 Amino acid Ala 226 on Rhce and RhCe protein is critical but requirements for expression of e antigen are not fully understood The presence of Cys 16 in Rhce weakens the expression of e antigen2. Effect of enzymes/chemicals on e antigen on intact RBCs Ficin/papain Resistant (↑↑) Trypsin Resistant (↑) ␣-Chymotrypsin Resistant (↑) Pronase Resistant (↑↑) Sialidase Resistant DTT 200 mM Resistant Acid Resistant 137

Rh blood group system In vitro characteristics of alloanti-e Immunoglobulin class Most IgG, some IgM Optimal technique IAT; enzymes Complement binding No Clinical significance of alloanti-e Transfusion reaction Mild to moderate/delayed/hemoglobinuria HDN Rare, usually mild Autoanti-e Common. Comments Alloanti-e-like antibodies may be made by people with eϩ RBCs lacking some e epitopes. This occurs more frequently in Blacks than in Caucasians3. Several e variants, in people at risk of immunization against lacking Rh epitopes, have been defined with monoclonal anti-e and molecular studies4,5. Reaction of monoclonal anti-e with RBCs expressing e-variant haplotypes2,4 Haplotype MS16 MS21 MS62/MS63 MS69 MS70 hrSϪ (ceMo) W W 0 00 Wϩ hrSϪ (ceAR) ϩ ϩ 0 ϩϩ ϩ0 hrSϪ (ceEK) ϩ ϩ ϩ 0 NT W0 hrBϪ (ceS) ϩϩ ϩ C=RNys16 (ce) 0ϩ W W0 0 Not expressed on RBCs from non-human primates. References 1 Cartron, J.-P. (1994) Blood Rev. 8, 199–212. 2 Westhoff, C.M. et al. (2001) Br. J. Haematol. 113, 666–671. 3 Issitt, P.D. (1991) Immunohematology 7, 29–36. 4 Noizat-Pirenne, F. et al. (2002) Blood 100, 4223–4231. 5 Noizat-Pirenne, F. et al. (2001) Br. J. Haematol. 113, 672–679. 138

Rh blood group system f ANTIGEN Terminology RH6 (004.006) ce, hr ISBT symbol (number) Reported in 1953 and named with the next Other names letter of the alphabet when it was thought History that c and e in cis were required for its expression Occurrence 65% Caucasians 92% Blacks 12% Asians Expressed Expression See system pages for unusual Rh complexes Cord RBCs Altered Molecular basis associated with f antigen Requirements for expression of antigen are not understood. Effect of enzymes/chemicals on f antigen on intact RBCs Ficin/papain Resistant Trypsin Resistant ␣-Chymotrypsin Resistant Pronase Resistant Sialidase Resistant DTT 200 mM Resistant Acid Resistant In vitro characteristics of alloanti-f Immunoglobulin class Most IgG, some IgM Optimal technique RT; IAT; enzymes Complement binding No Clinical significance of alloanti-f Transfusion reaction Mild/delayed/hemoglobinuria HDN Mild 139

Rh blood group system Autoanti-f Yes. Comments The f antigen, an example of a compound antigen, is expressed on RBCs having c (RH4) and e (RH5) antigens in the same haplotype (in cis), for example, R1r (DCe/dce), R0R0 (Dce/Dce), etc. The antigen is not expressed when c and e occur on separate haplotypes (in trans), e.g., R1R2 (DCe/DcE). However, RBCs of some people with the Dc- phenotype express f. Anti-f is frequently a component of sera containing anti-c or anti-e. Anti-f is useful in distinguishing DCE/dce from DCe/DcE. Apparent anti-f in Blacks may be anti-hrS (see RH19). Anti-f frequently fade in vitro and in vivo. Ce ANTIGEN RH7 (004.007) rhi Terminology Reported in 1958 when it was observed that C and e in cis were required for its ISBT symbol (number) expression Other names History 68% 27% Occurrence 92% Caucasians Blacks Asians Expression Expressed Cord RBCs Molecular basis associated with Ce antigen Requirements for expression of antigen are not understood. 140

Rh blood group system Effect of enzymes/chemicals on Ce antigen on intact RBCs Ficin/papain Resistant (↑↑) Trypsin Resistant (↑) ␣-Chymotrypsin Resistant (↑) Pronase Resistant (↑↑) Sialidase Resistant DTT 200 mM Resistant Acid Resistant In vitro characteristics of alloanti-Ce Immunoglobulin class IgG more common than IgM Optimal technique IAT; enzymes Complement binding No Clinical significance of alloanti-Ce Transfusion reaction Mild/delayed HDN Mild Comments Ce is a compound antigen expressed on RBCs with C and e in the same haplotype (in cis), for example, on DCe/dce (R1r) RBCs but not on DCE/dce (Rzr) RBCs. Anti-Ce is usually found in sera containing anti-C. Apparent anti-Ce in a Cϩ Black may be anti-hrB (see RH31). CW ANTIGEN RH8 (004.008) Willis, rhw Terminology Reported in 1946 and named because of the association with C and ‘W’ from ISBT symbol (number) ‘Willis’, the first proband whose RBCs Other names carried the antigen. For years was thought History to be antithetical to C. The weak C antigen on CW ϩ RBCs is due to an altered expres- sion of C rather than to ‘cross-reactivity’ of anti-CW. 141

Rh blood group system 2% 1% Occurrence 4% 9% Caucasians Blacks Finns Latvians Antithetical antigens CX (RH9), MAR (RH51)1 Expression Cord RBCs Expressed Altered Weaker on DCW See system pages for unusual Rh complexes Molecular basis associated with CW antigen2 Amino acid Arg 41 Nucleotide G at bp 122 in exon 1 CWϪ RBCs have Gln 41 and A at bp 122. See system pages. Effect of enzymes/chemicals on CW antigen on intact RBCs Ficin/papain Resistant (↑↑) Trypsin Resistant (↑) ␣-Chymotrypsin Resistant (↑) Pronase Resistant (↑↑) Sialidase Resistant DTT 200 mM Resistant Acid Resistant In vitro characteristics of alloanti-CW Immunoglobulin class IgG and IgM Optimal technique RT; IAT; enzymes Complement binding No Clinical significance of alloanti-CW Transfusion reaction Mild to severe; immediate/delayed HDN Mild to moderate 142

Rh blood group system Comments Anti-CW are often naturally-occurring and found in multi-specific sera. Most CWϩ are Cϩ; rare examples are CϪ. CW has been associated with D(C)CWe, D(C)CWE, (C)CWe, (C)CWE, DCW- and CWce haplotypes. References 1 Sistonen, P. et al. (1994) Vox Sang. 66, 287–292. 2 Mouro, I. et al. (1995) Blood 86, 1196–1201. CX ANTIGEN RH9 (004.009) rhX Terminology Reported in 1954 and named because of ISBT symbol (number) Other names the association with C and ‘X’ because X History was the next letter in the alphabet and the antigen had characteristics similar to CW. Was thought to be antithetical to C. The weak C antigen on CXϩ RBCs is due to an altered expression of C rather than to ‘cross-reactivity’ of anti-CX. Occurrence Less than 0.01%; more common in Finns. Antithetical antigens CW (RH8), MAR (RH51)1 Expression Expressed Cord RBCs 143

Rh blood group system Molecular basis associated with CX antigen2 Amino acid Thr 36 on RhCe and rarely Rhce Nucleotide A at bp 106 in exon 1 CXϪ RBCs have Ala 36 and G at bp 106 Effect of enzymes/chemicals on CX antigen on intact RBCs Ficin/papain Resistant (↑↑) Trypsin Resistant (↑) ␣-Chymotrypsin Resistant (↑) Pronase Resistant (↑↑) Sialidase Resistant DTT 200 mM Resistant Acid Resistant In vitro characteristics of alloanti-CX Immunoglobulin class IgG and IgM Optimal technique 37ЊC; IAT; enzymes Complement binding No Clinical significance of alloanti-CX Transfusion reaction No to moderate; immediate/delayed HDN Mild to moderate Comments Anti-CX are often naturally occurring and found in multi-specific sera. CXϩ are Cϩ except in the rare haplotype dCXces V Ϫ VSϩ found in Somalia. CX has been associated with D(C)CXe, (C)CXe and CXces haplotypes. References 1 Sistonen, P. et al. (1994) Vox Sang. 66, 287–292. 2 Mouro, I. et al. (1995) Blood 86, 1196–1201. V ANTIGEN RH10 (004.010) ces, hrV Terminology ISBT symbol (number) Other names 144



































































Rh blood group system Riv ANTIGEN Terminology RH45 (004.045) Reported in 1983 and named for the ISBT symbol (number) Puerto Rican family in which the antigen History and antibody were identified Occurrence Six propositi are known. Expression Expressed Cord RBCs Effect of enzymes/chemicals on Riv antigen on intact RBCs Ficin/papain Resistant (↑) Trypsin Presumed resistant ␣-Chymotrypsin Presumed resistant Pronase Presumed resistant Sialidase Presumed resistant DTT 200 mM Presumed resistant Acid Presumed resistant In vitro characteristics of alloanti-Riv Immunoglobulin class IgG Optimal technique 37ЊC; IAT; enzymes Complement binding No Clinical significance of alloanti-Riv HDN Mild; caused by the only example of anti-Riv in a serum which also contained anti-Goa (see RH30)1 Comments The Riv antigen is encoded by the rare gene complex DIVa(C)Ϫ; this complex also produces Goa (RH30), Rh33 (RH33), FPTT (RH50), the D antigen (RH1) characteristic of category DIVa, G (RH12), Nou (RH44), and very weak C (RH2), but no c (RH4), E (RH3), e (RH5) or f (RH6) antigen. Reference 1 Delehanty, C.L. et al. (1983) Transfusion 23, 410 (abstract). 178