The Gerbich blood group system: a review

Walker, P.S.; Reid, M.E.

doi:10.21307/immunohematology-2019-204

Abstract

Antigens in the Gerbich blood group system are expressed on glycophorin C (GPC) and glycophorin D (GPD), which are both encoded by a single gene, GYPC. The GYPC gene is located on the long arm of chromosome 2, and Gerbich antigens are inherited as autosomal dominant traits. There are 11 antigens in the Gerbich blood group system, six of high prevalence (Ge2, Ge3, Ge4, GEPL [Ge10*], GEAT [Ge11*], GETI [Ge12*]) and five of low prevalence (Wb [Ge5], Ls^a [Ge6], An^a [Ge7], Dh^a [Ge8], GEIS [Ge9]). GPC and GPD interact with protein 4.1R, contributing stability to the RBC membrane. Reduced levels of GPC and GPD are associated with hereditary elliptocytosis, and Gerbich antigens act as receptors for the malarial parasite Plasmodium falciparum. Anti-Ge2 and anti-Ge3 have caused hemolytic transfusion reactions, and anti-Ge3 has produced hemolytic disease of the fetus and newborn (HDFN). Immunohematology2010;26:60–65.

References

Rosenfield RE, Haber GV, Kissmeyer-Nielsen F, Jack JA, Sanger R, Race RR. Ge, a very common red-cell antigen. Br J Haematol 1960;6:344–9.10.1111/j.1365-2141.1960.tb06251.x
Search in Google Scholar Back to article
Cleghorn TE. The occurrence of certain rare blood group factors in Britain (thesis). Sheffield, UK: University of Sheffield, 1961.
Search in Google Scholar Back to article
Barnes R, Lewis TLT. A rare antibody (anti-Ge) causing haemolytic disease of the newborn. Lancet 1961;2:1285–6.10.1016/S0140-6736(61)91144-8
Search in Google Scholar Back to article
Booth PB, Albrey JA, Whittaker J, Sanger R. Gerbich blood group system: a useful genetic marker in certain Melanesians of Papua and New Guinea. Nature 1970;228:462.10.1038/228462a05482497
Search in Google Scholar Back to article
Booth PB, McLoughlin K. The Gerbich blood group system, especially in Melanesians. Vox Sang 1972;22:73–84.10.1111/j.1423-0410.1972.tb03968.x5011657
Search in Google Scholar Back to article
Zelinski T, Kaita H, Lewis M, Coghlan G, White L, Cartron JP. Distinction of the glycophorin C locus from the Diego, Dombrock and Yt blood group loci. Vox Sang 1991;61:62–4.10.1111/j.1423-0410.1991.tb00929.x1683068
Search in Google Scholar Back to article
Daniels GL, Anstee DJ, Cartron J-P, et al. Blood group terminology 1995. ISBT Working Party on terminology for red cell surface antigens. Vox Sang 1995;69:265–79.
Search in Google Scholar Back to article
Anstee DJ, Ridgwell K, Tanner MJ, Daniels GL, Parsons SF. Individuals lacking the Gerbich blood-group antigen have alterations in the human erythrocyte membrane sialoglycoproteins beta and gamma. Biochem J 1984;221:97–104.10.1042/bj221009711440076466322
Search in Google Scholar Back to article
el-Maliki B, Blanchard D, Dahr W, Beyreuther K, Cartron JP. Structural homology between glycophorins C and D of human erythrocytes. Eur J Biochem 1989;183:639–43.10.1111/j.1432-1033.1989.tb21093.x2776757
Search in Google Scholar Back to article
Reid ME, Spring FA. Molecular basis of glycophorin C variants and their associated blood group antigens. Transf Med 1994;4:139–46.10.1111/j.1365-3148.1994.tb00255.x7921050
Search in Google Scholar Back to article
Daniels G, King MJ, Avent ND, et al. A point mutation in the GYPC gene results in the expression of the blood group An^a antigen on glycophorin D but not on glycophorin C: further evidence that glycophorin D is a product of the GYPC gene. Blood 1993;82:3198–203.10.1182/blood.V82.10.3198.3198
Search in Google Scholar Back to article
Reid ME, Takakuwa Y, Conboy J, Tchernia G, Mohandas N. Glycophorin C content of human erythrocyte membrane is regulated by protein 4.1. Blood 1990;75:2229–34.10.1182/blood.V75.11.2229.2229
Search in Google Scholar Back to article
Alloisio N, Dalla Venezia N, Rana A, et al. Evidence that red blood cell protein p55 may participate in the skeleton-membrane linkage that involves protein 4.1 and glycophorin C. Blood 1993;82:1323–7.10.1182/blood.V82.4.1323.1323
Search in Google Scholar Back to article
Colin Y, Rahuel C, London J, et al. Isolation of cDNA clones and complete amino acid sequence of human erythrocyte glycophorin C. J Biol Chem 1986;261:229–33.10.1016/S0021-9258(17)42458-6
Search in Google Scholar Back to article
Mattei MG, Colin Y, Le Van Kim C, Mattei JF, Cartron JP. Localization of the gene for human erythrocyte glycophorin C to chromosome 2, q14-q21. Hum Genet 1986;74:420–2.10.1007/BF002804973793105
Search in Google Scholar Back to article
Le Van Kim C, Colin Y, Blanchard D, Dahr W, London J, Cartron JP. Gerbich blood group deficiency of the Ge:-1,-2,-3 and Ge:-1,-2,3 types. Immunochemical study and genomic analysis with cDNA probes. Eur J Biochem 1987;165:571–9.10.1111/j.1432-1033.1987.tb11478.x3595602
Search in Google Scholar Back to article
High S, Tanner MJ, Macdonald EB, Anstee DJ. Rearrangements of the red-cell membrane glycophorin C (sialoglycoprotein beta) gene. A further study of alterations in the glycophorin C gene. Biochem J 1989;262:47–54.10.1042/bj262004711332272818576
Search in Google Scholar Back to article
King M-J, Kosanke J, Reid ME, et al. Co-presence of a point mutation and a deletion of exon 3 in the glycophorin C gene and concomitant production of a Gerbich-related antibody. Transfusion 1997;37:1027–34.10.1046/j.1537-2995.1997.371098016440.x9354820
Search in Google Scholar Back to article
Poole J, Tilley L, Hudler P, et al. Novel mutations in GYPC giving rise to lack of Ge epitopes and anti-Ge production (abstract). Vox Sang 2008;95(Suppl 1):181.
Search in Google Scholar Back to article
Reid ME, Sullivan C, Taylor M, Anstee DJ. Inheritance of human-erythrocyte Gerbich blood group antigens. Am J Hum Genet 1987;41:1117–23.
Search in Google Scholar Back to article
Bloomfield L, Rowe GP, Green C. The Webb (Wb) antigen in South Wales donors. Hum Hered 1986;36:352–6.10.1159/0001536593539763
Search in Google Scholar Back to article
King MJ, Avent ND, Mallinson G, Reid ME. Point mutation in the glycophorin C gene results in the expression of the blood group antigen Dh^a. Vox Sang 1992;63:56–8.10.1111/j.1423-0410.1992.tb01220.x1413665
Search in Google Scholar Back to article
Yabe R, Uchikawa M, Tuneyama H, et al. Is: a new Gerbich blood group antigen located on the GPC and GPD (abstract). Vox Sang 2004;87(Suppl 3):79.
Search in Google Scholar Back to article
Chang S, Reid ME, Conboy J, Kan YW, Mohandas N. Molecular characterization of erythrocyte glycophorin C variants. Blood 1991;77:644–8.10.1182/blood.V77.3.644.644
Search in Google Scholar Back to article
Reid ME, Mawby W, King M-J, Sistonen P. Duplication of exon 3 in the glycoprotein C gene gives rise to the Ls^a blood group antigen. Transfusion 1994;34:966–9.10.1046/j.1537-2995.1994.341195065034.x7526492
Search in Google Scholar Back to article
Daniels GL. Studies on Gerbich negative phenotypes and Gerbich antibodies (abstract). Transfusion 1982;22:405.
Search in Google Scholar Back to article
Issitt P, Combs M, Carawan H, et al. Phenotypic association between Ge and Vel (abstract). Transfusion 1994;34(Suppl):60S.
Search in Google Scholar Back to article
Reid ME, Lomas-Francis C. Blood group antigens and antibodies: a guide to clinical relevance and technical tips. New York, NY: Star Bright Books, 2007.
Search in Google Scholar Back to article
McShane K, Chung A. A novel human alloantibody in the Gerbich system. Vox Sang 1989;57:205–9.10.1111/j.1423-0410.1989.tb00824.x
Search in Google Scholar Back to article
Anstee DJ, Parsons SF, Ridgwell K, et al. Two individuals with elliptocytic red cells apparently lack three minor erythrocyte membrane sialoglycoproteins. Biochem J 1984;218:615–19.10.1042/bj2180615
Search in Google Scholar Back to article
Daniels G, Shaw MA, Judson PA, et al. A family demonstrating inheritance of the Leach phenotype: a Gerbich-negative phenotype associated with elliptocytosis. Vox Sang 1986;50:117–21.10.1111/j.1423-0410.1986.tb04860.x
Search in Google Scholar Back to article
Mochizuki T, Tauxe WN, Ramsey G. In vivo cross-match by chromium-51 urinary excretion from labeled erythrocytes: a case of anti-Gerbich. J Nucl Med 1990;31:2042–4.
Search in Google Scholar Back to article
Hildebrandt M, Hell A, Etzel F, Genth R, Salama A. Determination and successful transfusion of anti-Gerbich-positive red blood cells in a patient with a strongly reactive anti-Gerbich antibody. Infusionsther Transfusionsmed 2000;27:154–6.10.1159/000025261
Search in Google Scholar Back to article
Selleng S, Selleng K, Zawadzinski C, Wollert HG, Yürek S, Greinacher A. Management of emergency cardiac surgery in a patient with alloanti-Ge2. Transfus Med 2009;19:50–2.10.1111/j.1365-3148.2008.00900.x
Search in Google Scholar Back to article
Pearson HA, Richards VL, Wylie BR, et al. Assessment of clinical significance of anti-Ge in an untransfused man. Transfusion 1991;31:257–9.10.1046/j.1537-2995.1991.31391165177.x
Search in Google Scholar Back to article
Micieli JA, Wang D, Denomme GA. Anti-glycophorin C induces mitochondrial membrane depolarization and a loss of extracellular regulated kinase 1/2 protein kinase activity that is prevented by pretreatment with cytochalasin D: implications for hemolytic disease of the fetus and newborn caused by anti-Ge3. Transfusion 2010;50:1761–5.10.1111/j.1537-2995.2010.02640.x
Search in Google Scholar Back to article
Vaughan JI, Warwick R, Letsky E, Nicolini U, Rodeck CH, Fisk NM. Erythropoietic suppression in fetal anemia because of Kell alloimmunization. Am J Obstet Gynecol 1994;171:247–52.10.1016/0002-9378(94)90477-4
Search in Google Scholar Back to article
Arndt PA, Garratty G, Daniels G, et al. Late onset neonatal anaemia due to maternal anti-Ge: possible association with destruction of eythroid progenitors. Transfus Med 2005;15:125–32.10.1111/j.0958-7578.2005.00562.x15859979
Search in Google Scholar Back to article
Blackall DP, Pesek GD, Montgomery MM, et al. Hemolytic disease of the fetus and newborn due to anti-Ge3: combined antibody-dependent hemolysis and erythroid precursor cell growth inhibition. Am J Perinatol 2008;25:541–5.10.1055/s-0028-108507218720327
Search in Google Scholar Back to article
Reynolds MV, Vengelen-Tyler V, Morel PA. Autoimmune hemolytic anemia associated with autoanti-Ge. Vox Sang 1981;41:61–7.10.1111/j.1423-0410.1981.tb01015.x
Search in Google Scholar Back to article
Shulman IA, Vengelen-Tyler V, Thompson JC, Nelson JM, Chen DC. Autoanti-Ge associated with severe autoimmune hemolytic anemia. Vox Sang 1990;59:232–4.10.1111/j.1423-0410.1990.tb00243.x
Search in Google Scholar Back to article
Sererat T, Veidt D, Arndt PA, Garratty G. Warm autoimmune hemolytic anemia associated with an IgM autoanti-Ge. Immunohematology 1998;14:26–9.10.21307/immunohematology-2019-650
Search in Google Scholar Back to article
Poole J, Reid ME, Banks J, Liew YW, Addy J, Longster G. Serological and immunochemical specificity of a human autoanti-Gerbich-like antibody. Vox Sang 1990;58:287–91.10.1159/000461136
Search in Google Scholar Back to article
Göttsche B, Salama A, Mueller-Eckhardt C. Autoimmune hemolytic anemia associated with an IgA autoanti-Gerbich. Vox Sang 1990;58:211–14.10.1111/j.1423-0410.1990.tb02093.x
Search in Google Scholar Back to article
Mudad R, Telen MJ. Biologic functions of blood group antigens. Curr Opin Hematol 1996;3:473–9.10.1097/00062752-199603060-00013
Search in Google Scholar Back to article
Daniels G. Functional aspects of red cell antigens. Blood Rev 1999;13:14–35.10.1016/S0268-960X(99)90020-6
Search in Google Scholar Back to article
Telen MJ, Le Van Kim C, Chung A, Cartron JP, Colin Y. Molecular basis for elliptocytosis associated with glycophorin C and D deficiency in the Leach phenotype. Blood 1991;78:1603–6.10.1182/blood.V78.6.1603.1603
Search in Google Scholar Back to article
Serjeantson SW. A selective advantage for the Gerbich-negative phenotype in malarious areas of Papua New Guinea. P N G Med J 1989;32:5–9.
Search in Google Scholar Back to article
Patel SS, Mehlotra RK, Kastens W, Mgone CS, Kazura JW, Zimmerman PA. The association of the glycophorin C exon 3 deletion with ovalocytosis and malaria susceptibility in the Wosera, Papua New Guinea. Blood 2001;98:3489–91.10.1182/blood.V98.12.3489
Search in Google Scholar Back to article
Maier AG, Duraisingh MT, Reeder JC, et al. Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations. Nat Med 2003;9:87–92.10.1038/nm807372882512469115
Search in Google Scholar Back to article
Mayer DC, Jiang L, Achur RN, Kakizaki I, Gowda DC, Miller LH. The glycophorin C N-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL. Proc Natl Acad Sci U S A 2006;103:2358–62.10.1073/pnas.0510648103141372216461900
Search in Google Scholar Back to article

The Gerbich blood group system: a review

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