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Published in: Immunity & Ageing 1/2018

Open Access 01-12-2018 | Research

Association of immunoglobulin GM allotypes with longevity in long-living individuals from Southern Italy

Authors: Annibale A. Puca, Anna Ferrario, Anna Maciag, Giulia Accardi, Anna Aiello, Caterina Maria Gambino, Giuseppina Candore, Calogero Caruso, Aryan M. Namboodiri, Janardan P. Pandey

Published in: Immunity & Ageing | Issue 1/2018

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Abstract

Background

The aim of this study was to analyse the role of GM allotypes, i.e. the hereditary antigenic determinants expressed on immunoglobulin polypeptide chains, in the attainment of longevity. The role played by immunoglobulin allotypes in the control of immune responses is well known as well as the role of an efficient immune response in longevity achievement. So, it is conceivable that particular GM allotypes may contribute to the generation of an efficient immune response that supports successful ageing, hence longevity.

Methods

In order to show if GM allotypes play a role in the achievement of longevity, we typed the DNA of 95 Long-living individuals (LLIs) and 96 young control individuals (YCs) from South Italy for GM3/17 and GM23+/− alleles.

Results

To demonstrate the role of GM allotypes in the attainment of longevity we compared genotype and allele frequencies of GM allotypes between LLIs and YCs. A global chi-square test (3 × 2) shows that the distribution of genotypes at the GM 3/17 locus is highly significantly different in LLIs from that observed in YCs (p < 0.0001). The 2 × 2 chi-square test shows that the carriers of the GM3 allele contribute to this highly significant difference. Accordingly, GM3 allele is significantly overrepresented in LLIs. No significant differences were instead observed regarding GM23 allele.

Conclusion

These preliminary results show that GM3 allotype is significantly overrepresented in LLIs. To best of our knowledge, this is the first study performed to assess the role of GM allotypes in longevity. So, it should be necessary to verify the data in a larger sample of individuals to confirm GM role in the attainment of longevity.
Literature
1.
go back to reference Oxelius VA, Pandey JP. Human immunoglobulin constant heavy G chain (IGHG) (Fcγ) (GM) genes, defining innate variants of IgG molecules and B cells, have impact on disease and therapy. Clin Immunol. 2013;149:475–86.CrossRef Oxelius VA, Pandey JP. Human immunoglobulin constant heavy G chain (IGHG) (Fcγ) (GM) genes, defining innate variants of IgG molecules and B cells, have impact on disease and therapy. Clin Immunol. 2013;149:475–86.CrossRef
2.
go back to reference 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;136:790–8.CrossRef 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;136:790–8.CrossRef
3.
go back to reference Pandey JP, Li Z. The forgotten tale of immunoglobulin allotypes in cancer risk and treatment. Exp Hematol Oncol. 2013;2:6.CrossRef Pandey JP, Li Z. The forgotten tale of immunoglobulin allotypes in cancer risk and treatment. Exp Hematol Oncol. 2013;2:6.CrossRef
4.
go back to reference Accardi G, Caruso C. Immune-inflammatory responses in the elderly: an update. Immun Ageing. 2018;15:11.CrossRef Accardi G, Caruso C. Immune-inflammatory responses in the elderly: an update. Immun Ageing. 2018;15:11.CrossRef
5.
go back to reference Pandey JP, Namboodiri AM, Nietert PJ, Yoshimura R, Hori H. Immunoglobulin genotypes and cognitive functions in schizophrenia. Immunogenetics. 2018;70:67–72.CrossRef Pandey JP, Namboodiri AM, Nietert PJ, Yoshimura R, Hori H. Immunoglobulin genotypes and cognitive functions in schizophrenia. Immunogenetics. 2018;70:67–72.CrossRef
6.
go back to reference Caruso C, Accardi G, Virruso C, Candore G. Sex, gender and immunosenescence: a key to understand the different lifespan between men and women? Immun Ageing. 2013;10:20.CrossRef Caruso C, Accardi G, Virruso C, Candore G. Sex, gender and immunosenescence: a key to understand the different lifespan between men and women? Immun Ageing. 2013;10:20.CrossRef
7.
go back to reference Puca AA, Spinelli C, Accardi G, Villa F, Caruso C. Centenarians as a model to discover genetic and epigenetic signatures of healthy ageing. Mech Ageing Dev. 2018;174:95–102.CrossRef Puca AA, Spinelli C, Accardi G, Villa F, Caruso C. Centenarians as a model to discover genetic and epigenetic signatures of healthy ageing. Mech Ageing Dev. 2018;174:95–102.CrossRef
8.
go back to reference Ferrario A, Villa F, Malovini A, Araniti F, Puca AA. The application of genetics approaches to the study of exceptional longevity in humans: potential and limitations. Immun Ageing. 2012;9:7.CrossRef Ferrario A, Villa F, Malovini A, Araniti F, Puca AA. The application of genetics approaches to the study of exceptional longevity in humans: potential and limitations. Immun Ageing. 2012;9:7.CrossRef
9.
go back to reference Bae H, Gurinovich A, Malovini A, Atzmon G, Andersen SL, Villa F, Barzilai N, Puca A, Perls TT, Sebastiani P. Effects of FOXO3 polymorphisms on survival to extreme longevity in four centenarian studies. J Gerontol A Biol Sci Med Sci. 2018;73:1439–47.CrossRef Bae H, Gurinovich A, Malovini A, Atzmon G, Andersen SL, Villa F, Barzilai N, Puca A, Perls TT, Sebastiani P. Effects of FOXO3 polymorphisms on survival to extreme longevity in four centenarian studies. J Gerontol A Biol Sci Med Sci. 2018;73:1439–47.CrossRef
10.
go back to reference Sebastiani P, Gurinovich A, Bae H, Andersen S, Malovini A, Atzmon G, Villa F, Kraja AT, Ben-Avraham D, Barzilai N, Puca A, Perls TT. Four genome-wide association studies identify new extreme longevity variants. J Gerontol A Biol Sci Med Sci. 2017;72:1453–64.CrossRef Sebastiani P, Gurinovich A, Bae H, Andersen S, Malovini A, Atzmon G, Villa F, Kraja AT, Ben-Avraham D, Barzilai N, Puca A, Perls TT. Four genome-wide association studies identify new extreme longevity variants. J Gerontol A Biol Sci Med Sci. 2017;72:1453–64.CrossRef
11.
go back to reference Carapelli R, Rando A, Iannelli D, Scala F, Chiofalo I. Age influenced IgG3 allotype in sheep. Immunol Lett. 1982;(6):301–4. Carapelli R, Rando A, Iannelli D, Scala F, Chiofalo I. Age influenced IgG3 allotype in sheep. Immunol Lett. 1982;(6):301–4.
12.
go back to reference de Vries RR, Meera Khan P, Bernini LF, van Loghem E, van Rood JJ. Genetic control of survival in epidemics. J Immunogenet. 1979;6:271–87.CrossRef de Vries RR, Meera Khan P, Bernini LF, van Loghem E, van Rood JJ. Genetic control of survival in epidemics. J Immunogenet. 1979;6:271–87.CrossRef
13.
go back to reference Villa F, Carrizzo A, Spinelli CC, Ferrario A, Malovini A, Maciąg A, Damato A, Auricchio A, Spinetti G, Sangalli E, Dang Z, Madonna M, Ambrosio M, Sitia L, Bigini P, Calì G, Schreiber S, Perls T, Fucile S, Mulas F, Nebel A, Bellazzi R, Madeddu P, Vecchione C, Puca AA. Genetic analysis reveals a longevity-associated protein modulating endothelial function and angiogenesis. Circ Res. 2015;117:333–45.CrossRef Villa F, Carrizzo A, Spinelli CC, Ferrario A, Malovini A, Maciąg A, Damato A, Auricchio A, Spinetti G, Sangalli E, Dang Z, Madonna M, Ambrosio M, Sitia L, Bigini P, Calì G, Schreiber S, Perls T, Fucile S, Mulas F, Nebel A, Bellazzi R, Madeddu P, Vecchione C, Puca AA. Genetic analysis reveals a longevity-associated protein modulating endothelial function and angiogenesis. Circ Res. 2015;117:333–45.CrossRef
14.
go back to reference Moraru M, Black LE, Muntasell A, Portero F, López-Botet M, Reyburn HT, Pandey JP, Vilches C. NK cell and Ig interplay in defense against herpes simplex virus type 1: epistatic interaction of CD16A and IgG1 Allotypes of variable affinities modulates antibody-dependent cellular cytotoxicity and susceptibility to clinical reactivation. J Immunol. 2015;195:1676–84.CrossRef Moraru M, Black LE, Muntasell A, Portero F, López-Botet M, Reyburn HT, Pandey JP, Vilches C. NK cell and Ig interplay in defense against herpes simplex virus type 1: epistatic interaction of CD16A and IgG1 Allotypes of variable affinities modulates antibody-dependent cellular cytotoxicity and susceptibility to clinical reactivation. J Immunol. 2015;195:1676–84.CrossRef
15.
go back to reference Di Bona D, Accardi G, Aiello A, Bilancia M, Candore G, Colomba C, Caruso C, Duro G, Gambino CM, Macchia L, Pandey JP. Association between γ marker, human leucocyte antigens and killer immunoglobulin-like receptors and the natural course of human cytomegalovirus infection: a pilot study performed in a Sicilian population. Immunology. 2018;153:523–31.CrossRef Di Bona D, Accardi G, Aiello A, Bilancia M, Candore G, Colomba C, Caruso C, Duro G, Gambino CM, Macchia L, Pandey JP. Association between γ marker, human leucocyte antigens and killer immunoglobulin-like receptors and the natural course of human cytomegalovirus infection: a pilot study performed in a Sicilian population. Immunology. 2018;153:523–31.CrossRef
16.
go back to reference Siscovick DS, Schwartz SM, Corey L, Grayston JT, Ashley R, Wang SP, Psaty BM, Tracy RP, Kuller LH, Kronmal RA. Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults: the cardiovascular health study. Circulation. 2000;102:2335–40.CrossRef Siscovick DS, Schwartz SM, Corey L, Grayston JT, Ashley R, Wang SP, Psaty BM, Tracy RP, Kuller LH, Kronmal RA. Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults: the cardiovascular health study. Circulation. 2000;102:2335–40.CrossRef
17.
go back to reference Savva GM, Pachnio A, Kaul B, Morgan K, Huppert FA, Brayne C, Moss PA. Medical Research Council cognitive function and ageing study. Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell. 2013;12:381–7.CrossRef Savva GM, Pachnio A, Kaul B, Morgan K, Huppert FA, Brayne C, Moss PA. Medical Research Council cognitive function and ageing study. Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell. 2013;12:381–7.CrossRef
18.
go back to reference Monastero R, Caruso C, Vasto S. Alzheimer's disease and infections, where we stand and where we go. Immun Ageing. 2014;11:26.CrossRef Monastero R, Caruso C, Vasto S. Alzheimer's disease and infections, where we stand and where we go. Immun Ageing. 2014;11:26.CrossRef
19.
go back to reference Barnes LL, Capuano AW, Aiello AE, Turner AD, Yolken RH, Torrey EF, Bennett DA. Cytomegalovirus infection and risk of Alzheimer disease in older black and white individuals. J Infect Dis. 2015;211:230–7.CrossRef Barnes LL, Capuano AW, Aiello AE, Turner AD, Yolken RH, Torrey EF, Bennett DA. Cytomegalovirus infection and risk of Alzheimer disease in older black and white individuals. J Infect Dis. 2015;211:230–7.CrossRef
20.
go back to reference Solana R, Tarazona R, Aiello AE, Akbar AN, Appay V, Beswick M, Bosch JA, Campos C, Cantisán S, Cicin-Sain L, Derhovanessian E, Ferrando-Martínez S, Frasca D, Fulöp T, Govind S, Grubeck-Loebenstein B, Hill A, Hurme M, Kern F, Larbi A, López-Botet M, Maier AB, McElhaney JE, Moss P, Naumova E, Nikolich-Zugich J, Pera A, Rector JL, Riddell N, Sanchez-Correa B, Sansoni P, Sauce D, van Lier R, Wang GC, Wills MR, Zieliński M, Pawelec G. CMV and Immunosenescence: from basics to clinics. Immun Ageing. 2012;9:23.CrossRef Solana R, Tarazona R, Aiello AE, Akbar AN, Appay V, Beswick M, Bosch JA, Campos C, Cantisán S, Cicin-Sain L, Derhovanessian E, Ferrando-Martínez S, Frasca D, Fulöp T, Govind S, Grubeck-Loebenstein B, Hill A, Hurme M, Kern F, Larbi A, López-Botet M, Maier AB, McElhaney JE, Moss P, Naumova E, Nikolich-Zugich J, Pera A, Rector JL, Riddell N, Sanchez-Correa B, Sansoni P, Sauce D, van Lier R, Wang GC, Wills MR, Zieliński M, Pawelec G. CMV and Immunosenescence: from basics to clinics. Immun Ageing. 2012;9:23.CrossRef
21.
go back to reference Itzhaki RF. Herpes simplex virus type 1 and Alzheimer's disease: increasing evidence for a major role of the virus. Front Aging Neurosci. 2014;6:202.CrossRef Itzhaki RF. Herpes simplex virus type 1 and Alzheimer's disease: increasing evidence for a major role of the virus. Front Aging Neurosci. 2014;6:202.CrossRef
22.
go back to reference Parry HM, Zuo J, Frumento G, Mirajkar N, Inman C, Edwards E, Griffiths M, Pratt G, Moss P. Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years. Immun Ageing. 2016;13:1.CrossRef Parry HM, Zuo J, Frumento G, Mirajkar N, Inman C, Edwards E, Griffiths M, Pratt G, Moss P. Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years. Immun Ageing. 2016;13:1.CrossRef
23.
go back to reference Pandey JP. Immunoglobulin GM genes, cytomegalovirus Immunoevasion, and the risk of glioma, neuroblastoma, and breast Cancer. Front Oncol. 2014;4:236.CrossRef Pandey JP. Immunoglobulin GM genes, cytomegalovirus Immunoevasion, and the risk of glioma, neuroblastoma, and breast Cancer. Front Oncol. 2014;4:236.CrossRef
24.
go back to reference Pandey JP, Kistner-Griffin E, Radwan FF, Kaur N, Namboodiri AM, Black L, Butler MA, Carreón T, Ruder AM. Immunoglobulin genes influence the magnitude of humoral immunity to cytomegalovirus glycoprotein B. J Infect Dis. 2014;210:1823–6.CrossRef Pandey JP, Kistner-Griffin E, Radwan FF, Kaur N, Namboodiri AM, Black L, Butler MA, Carreón T, Ruder AM. Immunoglobulin genes influence the magnitude of humoral immunity to cytomegalovirus glycoprotein B. J Infect Dis. 2014;210:1823–6.CrossRef
25.
go back to reference Pawelec G, Akbar A, Caruso C, Effros R, Grubeck-Loebenstein B, Wikby A. Is immunosenescence infectious? Trends Immunol. 2004;25:406–10.CrossRef Pawelec G, Akbar A, Caruso C, Effros R, Grubeck-Loebenstein B, Wikby A. Is immunosenescence infectious? Trends Immunol. 2004;25:406–10.CrossRef
26.
go back to reference Pawelec G, Akbar A, Caruso C, Grubeck-Loebenstein B, Solana R, Wikby A. Human immunosenescence: is it infectious? Immunol Rev. 2005;205:257–68.CrossRef Pawelec G, Akbar A, Caruso C, Grubeck-Loebenstein B, Solana R, Wikby A. Human immunosenescence: is it infectious? Immunol Rev. 2005;205:257–68.CrossRef
27.
go back to reference Vasto S, Caruso C. Immunity & Ageing: a new journal looking at ageing from an immunological point of view. Immun Ageing. 2004;1:1.CrossRef Vasto S, Caruso C. Immunity & Ageing: a new journal looking at ageing from an immunological point of view. Immun Ageing. 2004;1:1.CrossRef
28.
go back to reference Caruso C, Vasto S. Immunity and aging. In: Ratcliffe, MJH. (Editor in Chief), Encyclopedia of Immunobiology, 2016, Vol. 5, pp. 127–132. Oxford: Academic Press. Caruso C, Vasto S. Immunity and aging. In: Ratcliffe, MJH. (Editor in Chief), Encyclopedia of Immunobiology, 2016, Vol. 5, pp. 127–132. Oxford: Academic Press.
29.
go back to reference Rubino G, Bulati M, Aiello A, Aprile S, Gambino CM, Gervasi F, Caruso C, Accardi G. Sicilian centenarian offspring are more resistant to immune ageing. Aging Clin Exp Res. 2018; [Epub ahead of print]. Rubino G, Bulati M, Aiello A, Aprile S, Gambino CM, Gervasi F, Caruso C, Accardi G. Sicilian centenarian offspring are more resistant to immune ageing. Aging Clin Exp Res. 2018; [Epub ahead of print].
30.
go back to reference Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP, Listi F, Nuzzo D, Lio D, Caruso C. Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev. 2007;128:83–91.CrossRef Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP, Listi F, Nuzzo D, Lio D, Caruso C. Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev. 2007;128:83–91.CrossRef
31.
go back to reference Cevenini E, Caruso C, Candore G, Capri M, Nuzzo D, Duro G, Rizzo C, Colonna-Romano G, Lio D, Di Carlo D, Palmas MG, Scurti M, Pini E, Franceschi C, Vasto S. Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches. Curr Pharm Des. 2010;16:609–18.CrossRef Cevenini E, Caruso C, Candore G, Capri M, Nuzzo D, Duro G, Rizzo C, Colonna-Romano G, Lio D, Di Carlo D, Palmas MG, Scurti M, Pini E, Franceschi C, Vasto S. Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches. Curr Pharm Des. 2010;16:609–18.CrossRef
32.
go back to reference Candore G, Caruso C, Colonna-Romano G. Inflammation, genetic background and longevity. Biogerontology. 2010;11:565–73.CrossRef Candore G, Caruso C, Colonna-Romano G. Inflammation, genetic background and longevity. Biogerontology. 2010;11:565–73.CrossRef
33.
go back to reference Leonardi GC, Accardi G, Monastero R, Nicoletti F, Libra M. Ageing: from inflammation to cancer. Immun Ageing. 2018;15:1. Leonardi GC, Accardi G, Monastero R, Nicoletti F, Libra M. Ageing: from inflammation to cancer. Immun Ageing. 2018;15:1.
34.
go back to reference Listì F, Caruso C, Colonna-Romano G, Lio D, Nuzzo D, Candore G. HLA and KIR frequencies in Sicilian centenarians. Rejuvenation Res. 2010;13:314–8.CrossRef Listì F, Caruso C, Colonna-Romano G, Lio D, Nuzzo D, Candore G. HLA and KIR frequencies in Sicilian centenarians. Rejuvenation Res. 2010;13:314–8.CrossRef
35.
go back to reference Anselmi CV, Malovini A, Roncarati R, Novelli V, Villa F, Condorelli G, Bellazzi R, Puca AA. Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res. 2009;12:95–104.CrossRef Anselmi CV, Malovini A, Roncarati R, Novelli V, Villa F, Condorelli G, Bellazzi R, Puca AA. Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res. 2009;12:95–104.CrossRef
36.
go back to reference Balbín M, Grubb A, Abrahamson M, Grubb R. Determination of allotypes G1m (f) and G1m(z) at the genomic level by subclass-specific amplification of DNA and use of allele-specific probes. Exp Clin Immunogenet. 1991;8:88–95.PubMed Balbín M, Grubb A, Abrahamson M, Grubb R. Determination of allotypes G1m (f) and G1m(z) at the genomic level by subclass-specific amplification of DNA and use of allele-specific probes. Exp Clin Immunogenet. 1991;8:88–95.PubMed
37.
go back to reference Pandey JP, Namboodiri AM, Luo Y, Wu Y, Elston RC, Thomas DL, Rosen HR, Goedert JJ. Genetic markers of IgG influence the outcome of infection with hepatitis C virus. J Infect Dis. 2008;198:1334–6.CrossRef Pandey JP, Namboodiri AM, Luo Y, Wu Y, Elston RC, Thomas DL, Rosen HR, Goedert JJ. Genetic markers of IgG influence the outcome of infection with hepatitis C virus. J Infect Dis. 2008;198:1334–6.CrossRef
Metadata
Title
Association of immunoglobulin GM allotypes with longevity in long-living individuals from Southern Italy
Authors
Annibale A. Puca
Anna Ferrario
Anna Maciag
Giulia Accardi
Anna Aiello
Caterina Maria Gambino
Giuseppina Candore
Calogero Caruso
Aryan M. Namboodiri
Janardan P. Pandey
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2018
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-018-0134-7

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