The forgotten tale of immunoglobulin allotypes in cancer risk and treatment

Experimental Hematology & Oncology

Zihai Li¹  Janardan P Pandey¹ 

[1] Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29466, USA

关键词: GVL;    Immunosurveillance;    Isoallotypes;    CDC;    ADCC;    IGHG genes;    GM and KM allotypes;   

Others  :  812497
DOI  :  10.1186/2162-3619-2-6

 received in 2013-01-11, accepted in 2013-02-13,  发布年份 2013

【 摘 要 】

Monoclonal antibody (mAb) has fulfilled the promise of being the “Magic Bullet” in oncology with the clinical success of mAbs against CD20, Her-2/neu, epidermal growth factor receptor, vascular endothelial cell growth factor and others in a variety of cancers. Most manufacturers of mouse-human chimeric antibodies (and most immunologists) have treated the constant region of human immunoglobulin (Ig) as if it were naturally monomorphic and therefore not immunogenic in humans. In fact, the constant region of Ig heavy and light chain is highly polymorphic, and yet Ig haplotypes are usually not defined by genome-wide association studies nor are they considered to be important for optimizing mAb therapy. We hereby summarize evidence that Ig allotypes are important and biologically relevant in that they contribute to the etiopathogenesis of many malignant, infectious, and autoimmune diseases. Because Ig allotypes differ from each other in engaging Fc receptor, we argue that future development of effective mAb therapy for cancer should take a patient-specific approach by using the correct allotype for each patient to maximize the efficacy of this therapy.

【 授权许可】

   
2013 Pandey and Li; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Wang AC, Mathur S, Pandey JP, Siegal FP, Middaugh CR, Litman GW: Hv (l), a variable-region genetic marker of human immunoglobulin heavy chains. Science 1978, 200:327-329.
• [2]Lefranc MP, Lefranc G: Human Gm, Km, and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism. Methods Mol Biol 2012, 882:635-680.
• [3]van der Neut KM, Schuurman J, Losen M, Bleeker WK, Martínez-Martínez P, Vermeulen E, den Bleker TH, Wiegman L, Vink T, Aarden LA, De Baets MH, van de Winkel JG, Aalberse RC, Parren PW: Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 2007, 317:1554-1557.
• [4]Brusco A, Saviozzi S, Cinque F, DeMarchi M, Boccazzi C, de Lange G, van Leeuwen AM, Carbonara AO: Molecular characterization of immunoglobulin G4 gene isoallotypes. Eur J Immunogenet 1998, 25:349-355.
• [5]Labrijn AF, Rispens T, Meesters J, Rose RJ, den Bleker TH, Loverix S, van den Bremer ET, Neijssen J, Vink T, Lasters I, Aalberse RC, Heck AJ, van de Winkel JG, Schuurman J, Parren PW: Species-specific determinants in the IgG CH3 domain enable Fab-arm exchange by affecting the noncovalent CH3-CH3 interaction strength. J Immunol 2011, 187:3238-3246.
• [6]Pandey JP: Genetic markers of IgG as potential risk factors for IgG4-related disease. J Rheumatol 2048, 2012:39.
• [7]Lederberg J: J.B.S. Haldane (1949) on infectious disease and evolution. Genetics 1999, 153:1-3.
• [8]Klein G: Toward a genetics of cancer resistance. Proc Natl Acad Sci USA 2009, 106:859-863.
• [9]Nakao Y, Matsumoto H, Miyazaki T, Watanabe S, Mukojima T, Kawashima R, Fujita T, Tsuji K: Immunoglobulin G heavy-chain allotypes as possible genetic markers for human cancer. J Natl Cancer Inst 1981, 67:47-50.
• [10]Pandey JP, Ebbesen P, Bulow S, Svendsen LB, Fudenberg HH: IgG heavy-chain (Gm) allotypes in familial polyposis coli. Am J Hum Genet 1986, 39:133-136.
• [11]Pandey JP, Johnson AH, Fudenberg HH, Amos DB, Gutterman JU, Hersh EM: HLA antigens and immunoglobulin allotypes in patients with malignant melanoma. Hum Immunol 1981, 2:185-190.
• [12]Ilić V, Milosević-Jovcić N, Marković D, Petrović S, Stefanović G: A biased Gm haplotype and Gm paraprotein allotype in multiple myeloma suggests a role for the Gm system in myeloma development. Int J Immunogenet 2007, 34:119-125.
• [13]Pandey JP, Kistner-Griffin E, Iwasaki M, Bu S, Deepe R, Black L, Kasuga Y, Hamada GS, Tsugane S: Genetic markers of immunoglobulin G and susceptibility to breast cancer. Hum Immunol 2012, 73:1155-1158.
• [14]Pandey JP: Immunoglobulin GM and KM allotypes and vaccine immunity. Vaccine 2001, 19:613-617.
• [15]Pandey JP, Astemborski J, Thomas DL: Epistatic effects of immunoglobulin GM and KM allotypes on outcome of infection with hepatitis C virus. J Virol 2004, 78:4561-4565.
• [16]Granoff DM, Boies E, Squires J, Pandey JP, Suarez B, Oldfather J, Rodey GE: Interactive effect of genes associated with immunoglobulin allotypes and HLA specificities on susceptibility to Haemophilus influenzae disease. J Immunogenet 1984, 11:181-188.
• [17]de Vries RRP, Meera Khan P, Bernini LF, van Loghem E, van Rood J: Genetic control of survival in epidemics. J Immunogenet 1979, 6:271-287.
• [18]Deepe RN, Kistner-Griffin E, Martin JN, Deeks SG, Pandey JP: Epistatic interactions between Fc (GM) and FcγR genes and the host control of human immunodeficiency virus replication. Hum Immunol 2012, 73:263-266.
• [19]Pandey JP, Cooper GS, Treadwell EL, Gilkeson GS, St Clair EW, Dooley MA: Immunoglobulin GM and KM allotypes in systemic lupus erythematosus. Exp Clin Immunogenet 2001, 18:117-122.
• [20]Pandey JP, Goust JM, Salier JP, Fudenberg HH: Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis. J Clin Invest 1981, 67:1797-1800.
• [21]Gilhus NE, Pandey JP, Gaarder PI, Aarli JA: Immunoglobulin allotypes in myasthenia gravis patients with a thymoma. J Autoimmun 1990, 3:299-305.
• [22]Dugoujon JM, Cambon-Thomsen A: Immunoglobulin allotypes (GM and KM) and their interactions with HLA antigens in autoimmune diseases: a review. Autoimmunity 1995, 22:245-260.
• [23]Kagnoff MF, Weiss JB, Brown RJ, Lee T, Schanfield MS: Immunoglobulin allotype markers in gluten-sensitive enteropathy. Lancet 1983, 1:952-953.
• [24]Galbraith GMP, Thiers BH, Pandey JP: Gm allotype associated resistance and susceptibility to alopecia areata. Clin Exp Immunol 1984, 56:149-152.
• [25]Pandey JP: Genetic polymorphism of Fc. Science 2006, 311:1376-1377.
• [26]Pandey JP: Candidate gene approach’s missing link. Science 2010, 329:1148.
• [27]Pandey JP: Genomewide association studies and assessment of risk of disease. N Engl J Med 2010, 363:2076-2077.
• [28]Pandey JP: Risk alleles in idiopathic membranous nephropathy. N Engl J Med 2073, 2011:364.
• [29]Buck D, Albrecht E, Aslam M, Goris A, Hauenstein N, Jochim A, Cepok S, Grummel V, Dubois B, Berthele A, Lichtner P, Gieger C, Winkelmann J, Hemmer B, International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium: Genetic variants in the immunoglobulin heavy chain locus are associated with the IgG index in multiple sclerosis. Ann Neurol 2013, 73:86-94.
• [30]Salier JP, Goust JM, Pandey JP, Fudenberg HH: Preferential synthesis of the G1m(1) allotype of IgG1 in the central nervous system of multiple sclerosis patients. Science 1981, 213:1400-1402.
• [31]Lieberman R, Stiffel C, Asofsky R, Mouton D, Biozzi G, Benacerraf B: Genetic factors controlling anti-sheep erythrocyte antibody response and immunoglobulin synthesis in backcross and F2 progeny of mice genetically selected for “high” or “low” antibody synthesis. J Exp Med 1972, 136:790-798.
• [32]Pandey JP, Luo Y, Elston RC, Wu Y, Hite Philp F, Astemborski J, Thomas DL, Netski DM: Immunoglobulin allotypes influence IgG antibody responses to hepatitis C virus envelope proteins E1 and E2. Hum Immunol 2008, 69:158-164.
• [33]Hoffman RW, Sharp GC, Irvin WS, Anderson SK, Hewett JE, Pandey JP: Association of immunoglobulin Km and Gm allotypes with specific antinuclear antibodies and disease susceptibility among connective tissue disease patients. Arthritis Rheum 1991, 34:453-458.
• [34]Kameda H, Pandey JP, Kaburaki J, Inoko H, Kuwana M: Immunoglobulin allotype gene polymorphisms in systemic sclerosis: interactive effect of MHC class II and Km genes on anticentromere antibody production. Ann Rheum Dis 1998, 57:366-370.
• [35]Pandey JP, Page GP, Silver RM, LeRoy EC, Bona CA: Anti-fibrillin-1 autoantibodies in systemic sclerosis are Gm and Km allotype restricted. Exp Clin Immunogenet 2001, 18:123-129.
• [36]Pertovaara M, Hurme M, Antonen J, Pasternack A, Pandey JP: Immunoglobulin KM and GM gene polymorphisms modify the clinical presentation of primary Sjögren’s syndrome. J Rheumatol 2004, 31:2175-2180.
• [37]O’Hanlon TP, Rider LG, Targoff IN, Malley JK, Pandey JP, Schiffenbauer A, Miller FW: Immunoglobulin gene polymorphisms and the idiopathic inflammatory myopathies: GM and KM profiles distinguish patients by age, race, clinical phenotypes and myositis autoantibodies. Arthritis Rheum 2008, 58:3239-3246.
• [38]Goldblatt D, Scadding GK, Lund VJ, Wade AM, Turner MW, Pandey JP: Association of Gm allotypes with the antibody response to the outer membrane proteins of a common upper respiratory tract organism, Moraxella catarrhalis. J Immunol 1994, 153:5316-5320.
• [39]Pandey JP, Shannon BT, Tsang KY, Fudenberg HH, Camblin JG: Heterozygosity at Gm loci associated with humoral immunity to osteosarcoma. J Exp Med 1982, 155:1228-1232.
• [40]Pandey JP, Nietert PJ, Mensdorff-Pouilly S, Klaamas K, Kurtenkov O: Immunoglobulin allotypes influence antibody responses to mucin 1 in patients with gastric cancer. Cancer Res 2008, 68:4442-4446.
• [41]Pandey JP, Nietert PJ, Klaamas K, Kurtenkov O: A genetic variant of immunoglobulin γ2 is strongly associated with natural immunity to mucin 1 in patients with breast cancer. Cancer Immunol Immunother 2009, 58:2025-2029.
• [42]Pandey JP, Namboodiri AM, Kurtenkov O, Nietert PJ: Genetic regulation of antibody responses to human epidermal growth factor receptor 2 in breast cancer. Hum Immunol 2010, 71:1124-1127.
• [43]Pandey JP, Namboodiri AM, Kistner-Griffin E, Iwasaki M, Kasuga Y, Hamada GS, Tsugane S: Racially restricted contribution of immunoglobulin Fcγ and Fcγ receptor genotypes to humoral immunity to human epidermal growth factor receptor 2 in breast cancer. Clin Exp Immunol 2013, 171:273-277.
• [44]Morahan G, Berek C, Miller JFAP: An idiotypic determinant formed by both immunoglobulin constant and variable regions. Nature 1983, 301:720-722.
• [45]Casadevall A, Pirofski LA: A new synthesis for antibody-mediated immunity. Nat Immunol 2012, 13:21-28.
• [46]Torres M, Fernandez-Fuentes N, Fiser A, Casadevall A: The immunoglobulin heavy chain constant region affects kinetic and thermodynamic parameters of antibody variable region interactions with antigen. J Biol Chem 2007, 282:13917-13927.
• [47]Stockmeyer B, Valerius T, Repp IR, Heijnen IA, Bühring HJ, Deo YM, Kalden JR, Gramatzki M, van de Winkel JG: Preclinical studies with FcγR bispecific antibodies and granulocyte colony-stimulating factor-primed neutrophils as effector cells against HER-2/neu over expressing breast cancer. Cancer Res 1997, 57:696-701.
• [48]Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, Laccabue D, Zerbini A, Camisa R, Bisagni G, Neri TM, Ardizzoni A: Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 2008, 26:1789-1796.
• [49]Bibeau F, Lopez-Crapez E, Di Fiore F, Thezenas S, Ychou M, Blanchard F, Lamy A, Penault-Llorca F, Frébourg T, Michel P, Sabourin JC, Boissière-Michot F: Impact of FcγRIIa-FcγRIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 2009, 27:1122-1129.
• [50]Taylor RJ, Chan SL, Wood A, Voskens CJ, Wolf JS, Lin W, Chapoval A, Schulze DH, Tian G, Strome SE: FcgammaRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 2009, 58:997-1006.
• [51]Namboodiri AM, Pandey JP: Differential inhibition of trastuzumab and cetuximab induced cytotoxicity of cancer cells by IgG1 expressing different GM allotypes. Clin Exp Immunol 2011, 166:361-365.
• [52]Lazar GA, Dang W, Karki S, Vafa O, Peng JS, Hyun L, Chan C, Chung HS, Eivazi A, Yoder SC, Vielmetter J, Carmichael DF, Hayes RJ, Dahiyat BI: Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci USA 2006, 103:4005-4010.
• [53]Weiner LM, Surana R, Wang S: Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 2010, 10:317-327.
• [54]Weiner LM, Murray JC, Shuptrine CW: Antibody-based immunotherapy of cancer. Cell 2012, 148:1081-1084.
• [55]Brüggemann M, Williams GT, Bindon CI, Clark MR, Walker MR, Jefferis R, Waldmann H, Neuberger MS: Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med 1987, 166:1351-1361.
• [56]Dziurzynski K, Chang SM, Heimberger AB, Kalejta RF, McGregor Dallas SR, Smit M, Soroceanu L, Cobbs CS: HCMV and Gliomas Symposium: Consensus on the role of human cytomegalovirus in glioblastoma. Neuro-Oncol 2012, 14:246-255.
• [57]Atalay R, Zimmermann A, Wagner M, Borst E, Benz C, Messerle M, Hengel H: Identification and expression of human cytomegalovirus transcription units coding for two distinct Fcgamma receptor homologs. J Virol 2002, 76:8596-8608.
• [58]Namboodiri AM, Pandey JP: The human cytomegalovirus TRL11/IRL11-encoded FcγR binds differentially to allelic variants of immunoglobulin G1. Arch Virol 2011, 156:907-910.
• [59]Atherton A, Armour KL, Bell S, Minson AC, Clark MR: The herpes simplex virus type 1 Fc receptor discriminates between IgG1 allotypes. Eur J Immunol 2000, 30:2540-2547.
• [60]Namboodiri AM, Budkowska A, Nietert PJ, Pandey JP: Fcγ receptor-like hepatitis C virus core protein binds differentially to IgG of discordant Fc (GM) genotypes. Mol Immunol 2007, 44:3805-3808.
• [61]Namboodiri AM, Nietert PJ, Pandey JP: Hepatitis C virus core protein discriminates between the two IgG2 allotypes. Viral Immunol 2008, 21:273-276.
• [62]Maillard P, Lavergne JP, Siberil S, Faure G, Roohvand F, Petres S, Teillaud JL, Budkowska A: Fcγ receptor-like activity of hepatitis C virus core protein. J Biol Chem 2004, 279:2430-2437.
• [63]Schmidt M, et al.: A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors. Clin Cancer Res 2012, 18:2695-2703.
• [64]Ockhuizen T, Pandey JP, Veltri RW, Arlen M, Fudenberg HH: Immunoglobulin allotypes in patients with squamous cell carcinoma of the head and neck. Cancer 1982, 49:2021-2024.
• [65]Czerwinski M, Siemaszko D, Siegel DL, Spitalnik SL: Only selected light chains combine with a given heavy chain to confer specificity for a model glycopeptide antigen. J Immunol 1998, 160:4406-4417.
• [66]Primi D, Drapier AM, Cazenave PA: Highly preferential VH-VL pairing in normal B cells results in antigen-independent selection of the available repertoire. J Immunol 1987, 138:1607-1612.
• [67]Biggar RJ, Pandey JP, Henle W, Nkrumah FK, Levine PH: Humoral immune response to Epstein-Barr virus antigens and immunoglobulin allotypes in African Burkitt lymphoma patients. Int J Cancer 1984, 33:577-580.
• [68]Pandey JP, Baker CJ, Kasper DL, Fudenberg HH: Two unlinked genetic loci interact to control the human immune response to type III group B streptococcal antigen. J Immunogenet 1984, 11:159-163.
• [69]Etto TL, Stewart LA, Muirhead J, Bailey M, Schwarer AP: Kappa immunoglobulin light chain polymorphisms and survival after allogeneic transplantation for B-cell malignancies: a potential graft-vs-leukaemia target. Tissue Antigens 2007, 69:56-61.
• [70]Fudenberg HH, Fudenberg BR: Antibody to hereditary human gamma-globulin (Gm) factor resulting from maternal-fetal incompatibility. Science 1964, 145:170-171.