Antigen-fact-book

Colton blood group system Autoanti-Co3 One example described as mimicking anti-Co3 made by non-Hodgkins lymphoma patient. Comments Poor immunogen, rarely found as a single specificity. RBCs from a baby with congenital dyserythropoietic anemia (CDA) were Co(aϪbϪ), In(aϪbϪ), AnWj– and had a weak expression of LW1,2. References 1 Parsons, S.F. et al. (1994) Blood 83, 860–868. 2 Agre, P. et al. (1994) J. Clin. Invest. 94, 1050–1058. 371

LW Landsteiner–Wiener blood group system Number of antigens 3 Terminology LW 016 ISBT symbol CD242 ISBT number ICAM-4 CD number Anti-LW, or ‘anti-Rh’ as it was called, was Other name produced in 1940. However, the phenotypic History relationship between LW and the RhD anti- gen delayed recognition that LW was an Phenotypes independent blood group system until 1963 Obsolete when it was named to honor Landsteiner LWϩ, Dϩ and Wiener who made anti-LW in rabbits LWϩ, DϪ and guinea pigs after immunizing them LWϪ, Dϩ or DϪ with blood from Macacus rhesus. In 1982, it LWϪ, Dϩ or DϪ became a three-antigen system. The LW1, LWϪ, Rhnull LW2, LW3 and LW4 terminology was changed when it was realized that anti-Nea (now called anti-LWb) detects an antigen antithetical to that recognized by anti-LW made by LW3 people (now called anti-LWa)1 Obsolete Current LW1 LW(aϩbϪ) or LW(aϩbϩ) LW2 LW(aϩbϪ) or LW(aϩbϩ) LW3 LW(aϪbϩ) LW4 LW(aϪbϪ) LW0 LW(aϪbϪ) Expression May be found in placenta Tissues 19p13.3 LW Gene2 3 exons distributed over 2.6 kbp of gDNA LW glycoprotein Chromosome Name Organization Product 372

Landsteiner–Wiener blood group system Gene map 3Ј * STOP ATG * LW 5/LW 7 (308A>G) encodes LWa/LWb (Gln70Arg) 100 bp Database accession numbers GenBank X93093 www.bioc.aecom.yu.edu/bgmut/index.htm Amino acid sequence MGSLFPLSLL FFLAAAYPGV GSALGRRTKR Ϫ01 AQSPKGSPLA PSGTSVPFWV RMSPEFVAVQ PGKSVQLNCS NSCPQPQNSS 50 LRTPLRQGKT LRGPGWVSYQ LLDVRAWSSL AHCLVTCAGK TRWATSRITA YKPPHSVILE PPVLKGRKYT LRCHVTQVFP VGYLVVTLRH GSRVIYSESL 100 ERFTGLDLAN VTLTYEFAAG PRDFWQPVIC HARLNLDGLV VRNSSAPITL 150 MLAWSPAPTA LASGSIAALV GILLTVGAAY LCKCLAMKSQ A 200 241 Antigen mutation(s) are numbered by counting Arg as 1. LW encodes a leader sequence of 30 amino acids. Carrier molecule3 1 NH2 I-set IgSF 70 LWa/LWb Gln/Arg I-set IgSF 208 RBC lipid bilayer 229 241 COOH 373

Landsteiner–Wiener blood group system Mr (SDS-PAGE) 37 000–43 000 CHO: N-glycan Four potential sites at residue 38, 48, 160, 193 CHO: O-glycan Present Cysteine residues Three pairs at residues 39/83, 43/87 and 123/180 Copies per RBC4 Dϩ 4400 (Adult) 5150 (cord) DϪ 2835 (Adult) 3620 (cord) Molecular basis of antigens5 Antigen Amino acid Exon Nt change Restriction LWa/LWb change 1 308AϾG enzyme Gln70Arg PvuϾII (ϩ/Ϫ) Function The LW glycoprotein is an intercellular adhesion molecule (ICAM-4) and a ligand for integrins. LW has 30% sequence identity with other ICAMs. ICAM-4 binds to CD11/CD18 (␣1␤2) integrin and LFA-1 leukocyte integrins ␣4␤1, ␣v␤1, ␣v␤5 and maybe ␣v␤36–8. Possible marker for lymphocyte matura- tion or differentiation. May assist in stabilizing erythroblastic islands during erythropoiesis. May be involved in removal of senescent RBCs3. Disease association LW antigens may be depressed during pregnancy and some diseases, for example, Hodgkin’s disease, lymphoma, leukemia and sarcoma3. Autoanti- LW is common in patients with warm AIHA. Expression of ICAM-4 is elevated on sickle RBCs and interaction between ICAM-4 and vascular endothelial cells may be involved in microvascular occlusions during painful crises of SCD. Phenotypes (% occurrence) Most populations Finns LW(aϩbϪ) 97% 93.9% LW(aϩbϩ) 3% 6.0% LW(aϪbϩ) Rare 0.1% Null: LW(aϪbϪ). Rhnull RBCs type LW(aϪbϪ) although LW is normal. 374

Landsteiner–Wiener blood group system There is a phenotypic relationship between LW and D antigens: In adults, DϪ RBCs have lower expression of LW antigens than Dϩ RBCs (ratio 1:1.5). In cord RBCs LW is strongly expressed in DϪ and Dϩ RBCs. Molecular basis of phenotypes2 Phenotype Basis LW(aϪbϪ) 346delACCTGCGCAG in exon 1 (codons 86–89); frameshift; Stop Comments LW antigens require intramolecular disulfide bonds and the presence of diva- lent cations, notably Mgϩϩ for expression9. Since Rhnull RBCs were the only cells that failed to elicit an antibody response in animals, they are presumed to be the only true LW(aϪbϪ). LW antigens have been detected on RBCs of chimpanzee, gorilla, orangutan, baboon and various species of monkey but not on RBCs of rabbit, mouse, rat, sheep, goat, horse and cattle. References 1 Sistonen, P. and Tippett, P. (1982) Vox Sang. 42, 252–255. 2 Hermand, P. et al. (1996) Blood 87, 2962–2967. 3 Parsons, S.F. et al. (1999) Baillieres Clin. Haematol. 12, 729–745. 4 Mallinson, G. et al. (1986) Biochem. J. 234, 649–652. 5 Hermand, P. et al. (1995) Blood 86, 1590–1594. 6 Bailly, P. et al. (1995) Eur. J. Immunol. 25, 3316–3320. 7 Spring, F.A. et al. (2001) Blood 98, 458–466. 8 Zennadi, R. et al. (2002). Blood 100 (Suppl., Part 1), 118a (abstract). 9 Bloy, C. et al. (1990) J. Biol. Chem. 265, 21482–21487. LWa ANTIGEN LW5 (016.005) LW, LW1 in Dϩ, LW2 in DϪ Terminology Named LWa in 1982 when the antithetical relationship to Nea (LWb) was recognized. ISBT symbol (number) LW1 to LW4 were made obsolete because Other names they had been used to designate phenotypes History 375

Landsteiner–Wiener blood group system Occurrence 100% All populations Antithetical antigen LWb (LW7) Expression Well expressed on D-positive and D-negative Cord RBCs Weak on DϪRBCs from adults Weak or absent on RBCs stored in EDTA Altered Molecular basis associated with LWa antigen1 Amino acid Gln 70 Nucleotide A at bp 308 in exon 1 Restriction enzyme Pvu II site Effect of enzymes/chemicals on LWa antigen on intact RBCs Ficin/papain Resistant Trypsin Resistant ␣-Chymotrypsin May be weakened Pronase Sensitive Sialidase Resistant DTT 200 mM/50 mM Sensitive/sensitive Acid Resistant In vitro characteristics of alloanti-LWa Immunoglobulin class IgG (usually); IgM Optimal technique RT or IAT Complement binding No Clinical significance of alloanti-LWa Transfusion reaction No to mild/delayed (Rare; DϪ, LWaϩ HDN RBCs survive well) No to mild (very rare) 376

Landsteiner–Wiener blood group system Autoanti-LWa Autoanti-LWa with suppression of LW antigens has been reported. Common in serum of patients with warm AIHA. Comment Antigen expression requires Mgϩϩ. Reference 1 Hermand, P. et al. (1995) Blood 86, 1590–1594. LWab ANTIGEN LW6 (016.006) Bigelow, Big, LW Terminology LW4 was renamed LWab when the LW blood group system was established ISBT symbol (number) Other names Well expressed on D-positive and History D-negative Weak on DϪ RBCs from adults Occurrence Weak or absent on RBCs stored in EDTA All populations: 100%. Expression Cord RBCs Altered Molecular basis associated with LWab antigen Not known. See system pages for molecular basis of LW(aϪbϪ) phenotype. Effect of enzymes/chemicals on LWab antigen on intact RBCs Ficin/papain Resistant Trypsin Resistant 377

Landsteiner–Wiener blood group system ␣-Chymotrypsin May be weakened Pronase Sensitive Sialidase Resistant DTT 200 mM/50 mM Sensitive/sensitive Acid Resistant In vitro characteristics of alloanti-LWab Immunoglobulin class IgG; IgM Optimal technique 37ЊC; IAT Complement binding No Clinical significance of alloanti-LWab Transfusion reaction No data HDN Mild Autoanti-LWab Autoanti-LWab with suppression of LW antigens occurs1. Common in serum of patients with warm AIHA. Comments Only one alloanti-LWab has been described in an LW(aϪbϪ) person with an LW(aϪbϪ) brother. When LW antigens are suppressed, the anti-LWab may mimic an alloantibody and is a more common specificity than autoanti-LWa. Antigen expression required Mgϩϩ. Reference 1 Storry, J.R. (1992) Immunohematology 8, 87–93. LWb ANTIGEN LW7 (016.007) Nea, LW3 Terminology Name changed from Nea when the anti- thetical relationship to LWa was recog- ISBT symbol (number) Other names nized in 1982 History 378

Landsteiner–Wiener blood group system Occurrence Estonians 8%, Finns 6%, Latvians and Lithuanians 5%, Poles and Russians 2% and other Europeans less than 1%1. Antithetical antigen LWa (LW5) Expression Well expressed on D-positive and D-negative Cord RBCs Weak on DϪ RBCs from adults Weak or absent on RBCs stored in EDTA Altered Molecular basis associated with LWb antigen2 Amino acid Arg 70 Nucleotide G at bp 308 in exon 1 Restriction enzyme Pvu II site last Effect of enzymes/chemicals on LWb antigen on intact RBCs Ficin/papain Resistant (↑↑) Trypsin Resistant (↑↑) ␣-Chymotrypsin May be weakened Pronase Sensitive Sialidase Resistant DTT 200 mM/50 mM Sensitive/sensitive Acid Resistant In vitro characteristics of alloanti-LWb Immunoglobulin class IgG; IgM Optimal technique 37ЊC; IAT Complement binding No Clinical significance of alloanti-LWb Transfusion reaction No to mild HDN No to mild 379

Landsteiner–Wiener blood group system Comment Antigen expression requires Mgϩϩ. References 1 Sistonen, P. et al. (1999) Hum Hered. 49, 154–158. 2 Hermand, P. et al. (1995) Blood 86, 1590–1594. 380

CH/RG Chido/Rodgers blood group system Number of antigens 9 Terminology CH/RG 017 ISBT symbol Named after the first antibody producers, ISBT number Chido and Rodgers. Anti-Ch was reported History in 1967 and when anti-Rg was described in 1976, there were obvious similarities between them. Ch and Rg appeared to be RBC antigens and were given blood group system status. However, the antigens were later located on the fourth compo- nent of complement (C4), which becomes bound to RBCs from the plasma Expression In plasma or serum GPA-deficient RBCs have a weak expres- Soluble form sion of Ch and Rg antigens Altered Gene 6p21.3 CH (C4B); RG(C4A) Chromosome C4A 41 exons distributed over 22 kpb of Name gDNA Organization C4B 41 exons distributed over 22 or 16 kbp of gDNA after loss of a 6.8 kbp intron Product C4A complement component (Rg) C4B complement component (Ch) Database accession numbers GenBank K02403; M59815; M59816; U24578 http://www.bioc.aecom.yu.edu/bgmut/index.htm Carrier molecule C4A and C4B are glycoproteins which are adsorbed onto the RBC membrane. C4A binds preferentially to protein and C4B to carbohydrate. C4A migrates 381

Chido/Rodgers blood group system more quickly in electrophoresis than C4B. C4A and C4B are 99% identical in their amino acid sequences. Ch and Rg antigens are located in the C4d region of C4B or C4A, respec- tively. C4d is a tryptic fragment of C4. The different antigens are usually identified in plasma by hemagglutina- tion inhibition studies. Molecular basis of antigens1 Ch/Rg Phenotype Amino acid residue Allotype Type 1054 1101 1102 1105 1106 1157 1188 1191 C4A*3 ChϪRgϩ Ch:Ϫ1,Ϫ2,Ϫ3, D P C L D N V L Ϫ4, Ϫ5,Ϫ6 Rg:1,2 C4A*1 ChϩRgϪ Ch:1,Ϫ2,3,Ϫ4, G P C L D S A R 5,6 Rg:-1,-2 C4A*3 ChϪRgϩ Ch:Ϫ1,Ϫ2,Ϫ3, D P C L D S V L WHϩ Ϫ4Ϫ5,6 Rg: 1,Ϫ42 C4B*3 ChϩRgϪ Ch:1,2,3,4,5, GL S I HSAR 6 Rg:Ϫ1,Ϫ2 C4B*1 ChϩRgϪ Ch:1,2,-3,4,5, G L S I HNA R Ϫ6 Rg:Ϫ1,Ϫ2 C4B*2 ChϩRgϪ Ch:1,Ϫ2,3,4,Ϫ5, D L S I H S A R 6 Rg:Ϫ1,Ϫ2 C4B*5 ChϩRgϩ Ch:Ϫ1,Ϫ2,Ϫ3,4, D L S I H S V L WHϩ Ϫ5, 6 Rg:1,Ϫ2 Function There are functional differences between C4A and C4B allotypes: C4A is more effective than C4B at solubilizing immune complexes and inhibiting immune precipitation. C4B binds more effectively to the RBC surface (through sialic acid) and thus is more effective at promoting hemolysis. A single amino acid substitution at position 1106 (aspartic acid for histidine) converts the func- tional activity of C4B to C4A2, whereas the substitution of cysteine for serine at position 1102 affects hemolytic activity and IgG binding. Disease association Inherited low levels of C4 may be a predisposing factor for diseases such as insulin-dependent diabetes and autoimmune chronic active hepatitis. Specific C4 allotypes and null genes have been associated with numerous autoimmune disorders including Graves’ disease and rheumatoid arthritis 382

Chido/Rodgers blood group system (for list, see reference 3). Lack of C4B (ChϪ) gives increased susceptibility to bacterial meningitis in children. RgϪ individuals (lack of C4A) have a much greater susceptibility for SLE. Phenotypes (% occurrence) Chido Most Rodgers Most antigens populations Japanese populations Japanese antigens CH/RG:1,2,3 88.2 75 CH/RG:11,12 95 100 0 CH/RG:1,Ϫ2,3 4.9 24 CH/RG:11,Ϫ12 3 0 CH/RG:1,2,Ϫ3 3.1 0 CH/RG:Ϫ11,Ϫ12 2 CH/RG:Ϫ1,Ϫ2,Ϫ3 3.8 1 CH/RG:Ϫ1,2,Ϫ3 rare 0 CH/RG:1,Ϫ2,Ϫ3 rare 0 Null: C4-deficient RBCs. Comments Antigens of this system are stable in stored serum or plasma. Phenotypes and antibodies of this system are most accurately defined by hemagglutination inhibition tests. RBCs coated with C4 (ϩC3) by use of low ionic strength 10% sucrose solu- tion give enhanced reactivity with anti-Ch and anti-Rg. Sialidase-treated RBCs do not take up C4. C4 molecule (adapted from Daniels4) C4a C4d α S S S S β S S γ References 1 Yu, C.Y. et al. (1988) Immunogenetics 27, 399–405. 2 Carroll, M.C. et al. (1990) Proc. Natl. Acad. Sci. USA 87, 6868–6872. 3 Moulds, J.M. (1994) In: Immunobiology of Transfusion Medicine (Garratty, G. ed) Marcel Dekker, Inc., New York, pp. 273–297. 4 Daniels, G. (1995) In: Molecular Basis of Human Blood Group Antigens (Cartron, J.-P. and Rouger, P. eds) Plenum Press, New York, pp. 397–419. 383

Chido/Rodgers blood group system Ch1 ANTIGEN CH/RG1 (017.001) Ch; Cha; Chido Terminology Named in 1967 after Mrs. Chido who made “anti-Chido” (considered a nebu- ISBT symbol (number) lous antibody) Other names History Occurrence 96% 99% Most populations Japanese Expression Absent or weak Weak on some dominant Lu(aϪbϪ) and Cord RBCs on GPA-deficient RBCs Altered Molecular basis associated with Ch1 antigen Requires alanine at residue 1188 and arginine at 1191 of C41,2. See system pages. Effect of enzymes/chemicals on Ch1 antigen on intact RBCs Ficin/papain Sensitive Trypsin Sensitive ␣-Chymotrypsin Sensitive Pronase Sensitive Sialidase Resistant DTT 200 mM Resistant Acid Resistant In vitro characteristics of alloanti-Ch1 Immunoglobulin class IgG (mostly IgG2 and IgG4) Optimal technique IAT Neutralization Antigen-positive serum or plasma Complement binding No 384