Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-26T17:41:20.842Z Has data issue: false hasContentIssue false
  • English
  • Français

Twin Studies in Auto-immune Disease

Published online by Cambridge University Press:  01 August 2014

R.D.G. Leslie  and
M. Hawa
R.D.G. Leslie*
Affiliation:
Department of Diabetes and Metabolism, St. Bartholomew's Hospital, London, UK
M. Hawa
Affiliation:
Department of Diabetes and Metabolism, St. Bartholomew's Hospital, London, UK
*
Department of Diabetes and Metabolism, Andrew Cudworth Laboratories, 3rdFloor, Dominion House, 59 Bartholomew Close, West Smithfield, London EC1A 7BE, UK

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Immune-mediated diseases affect up to 5% of the population and are a major cause of morbidity and mortality. These diseases can be organ specific, such as insulin-dependent diabetes (IDDM) and non-organ specific, such as Rheumatoid Arthritis (RA). Identical and non-identical twins have been used to establish whether these diseases are determined by genetic or environmental factors. The results of these studies have been collated in a new section of the Mendel Institute in Rome.

Diseases included in these studies included IDDM, RA, Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS) and Myasthenia. Striking differences in concordance rates between identical and non-identical twins in all these studies suggest that genetic factors are important in causing these diseases. All the diseases are known to be associated with HLA genes on chromosome 6 which may account for some or all of the genetic susceptibility. However, in the majority of pairs the affected twin has an unaffected co-twin. These observations suggest that non-genetically determined factors, probably environmental factors and not somatic mutations, are critical. The study of unaffected co-twins, who are at high disease-risk, has allowed the identification of changes which precede and predict the clinical disease. The immune-mediated destruction in many of these diseases is probably caused by T-lymphocytes. Twin studies have shown the importance of genetic factors in determining T-cell responses. Identical twins should, therefore, provide the perfect test bed to assess the role of T-cells in immune-mediated diseases.

Keywords

TwinsAuto-immuneT-IymphocytesAntibodies
Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 43 , Issue 1-2 , April 1994 , pp. 71 - 81
Copyright
Copyright © The International Society for Twin Studies 1994

References

REFERENCES

1. Aho, K, Koskenvuo, M, Tuominen, J, Kaprio, J (1986): Occurence of rheumatoid arthritis in a nationwide series of twins. J Rheumatol 13:899–902.Google Scholar
2. Alviggi, L, Johnston, C, Hoskins, PJ, Tee, DEH, Pyke, DA, Leslie, RDG, Vergani, D (1984): Pathogenesis of insulin-dependent diabetes: a role for activated T lymphocytes. Lancet ii: 4–6.Google Scholar
3. Beer, SF, Heaton, DA, Alberti, KGMM, Pyke, DA, Leslie, RDG (1990): Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins. Diabetologia 33:497–502.Google Scholar
4. Briant, L, Voustin, PA, Clayton, J, McDermott, M, Clanet, M, Cambon-Thomsen, A and the French Group on Multiple Sclerosis (1993): Multiple sclerosis susceptibility: Population and twin study of polymorphisms in the T-cell receptor β and y genes region. Autoimmunity vol 15:67–73.Google Scholar
5. Cains, J, Overbaugh, J, Miller, S (1988): The origins of mutants. Nature 335:142–145.Google Scholar
6. Christie, MR, Tun, RYM, Lo, S, Cassidy, D, Brown, TJ, Hollands, J, Shattock, M, Bottazzo, GF, Leslie, RDG (1992): Antibodies to GAD and tryptic fragments of islet 64K antigen as distinct markers for development of IDDM. Diabetes 41:782–787.Google Scholar
7. Dalton, TA, Bennet, JC (1992): Auto-immune disease and the major histocompatibility complex: therapeutic implications. Am J Med 92:183–188.Google Scholar
8. Deapen, D, Escalante, A, Weinrib, L, Horwitz, D, Bachman, B, Roy-burman, P, Walker, A, Mack, TM (1992): A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis and Rheumatism 35:311–318.Google Scholar
9. Ebers, GC, Bulman, DE, Sadovnick, AD, Paty, DW, Warren, S, Hader, W, Murray, TJ, Seland, TP, Duquette, P, Grey, T, Nelson, R, Nicolle, M, Brunet, D (1986): A population based study of multiple sclerosis in twins. New Eng J Med. 315:1638–1642.Google Scholar
10. Falconer, DS (1981): Introduction to quantitative genetics. Second Ed. New York: Longman, pp. 148–169.Google Scholar
11. Heaton, DA, Millward, BA, Gray, IP, Tun, Y, Hales, CN, Pyke, DA, Leslie, RDG (1987): Evidence of beta cell dysfunction which does not lead on to diabetes: a study of identical twins of insulin-dependent diabetics. Br Med J 294:145–146.Google Scholar
12. Hoskins, PJ, Leslie, RDG, Pyke, DA (1985): Height at diagnosis of diabetes in children: a study in identical twins. Br Med J 290:278–280.Google Scholar
13. Jarvinen, P, Kaprio, J, Makitalo, R, Koskenvuo, M, Aho, K (1992): Systemic lupus erythematosus and related systemic diseases in a nationwide twin cohort: an increased prevalence of disease in MZ twins and concordance of disease features. J Int Med 231:67–72.CrossRefGoogle Scholar
14. Kaprio, J, Tuomilehto, J, Koskenvuo, M, Romanov, K, Reunanen, A, Eriksson, J, Stengard, J, Kesaniemi, YA (1992): Concordance for Type 1 (insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia 35:1060–1067.Google Scholar
15. Khalil, I, d'Auriol, L, Gobet, M, Morin, L, Lepage, V, Deschamps, I, Park, MS, Degos, L, Galibert, F, Hors, J (1990): A combination of HLA-DQB Asp 57-Negative and HLA DQA Arg 52 confers susceptibility to insulin-dependent diabetes mellitus. J Clin Invest 85:1315–1319.Google Scholar
16. Kinnunen, E, Juntunen, J, Ketonen, L, Koskimies, S, Konttinen, YT, Salmi, T, Koskenvuo, M, Kaprio, J (1988): Genetic susceptibility to multiple sclerosis. A cotwin study of a nationwide series. Arch Neurol 45:1108–1111.CrossRefGoogle ScholarPubMed
17. Leslie, RDG, Lo, S, Millward, BA, Honour, J, Pyke, DA (1991): Decreased growth velocity before IDDM onset. Diabetes 40:211–216.Google Scholar
18. Leslie, RDG, Pyke, DA (1991): Escaping insulin-dependent diabetes. Br Med J 302:1103–1104.Google Scholar
19. Lo, SSS, Hawa, M, Beer, SF, Pyke, DA, Leslie, RDG (1992): Altered islet Betacell function before the onset of Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35:277–282.Google Scholar
20. Loveridge, JA, Rosenberg, WMC, Kirkwood, TBL, Bell, JI (1991): The genetic contribution to human T cell receptor repertoire. Immunology 74:246–250.Google ScholarPubMed
21. Martin, R, Voskuhl, R, Flerlage, M, McFarlin, DE, McFarland, HF (1993): Myelin basic protein-specific T-cell responses in identical twins discordant or concordant for multiple sclerosis. Ann Neurol 34:524–535.Google Scholar
22. Millward, BA, Alviggi, L, Hoskins, PJ, Johnston, D, Heaton, D, Bottazzo, GF, Vergani, D, Leslie, RDG, Pyke, DA (1986): Immune changes associated with insulin dependent diabetes may remit without causing diabetes: a study in identical twins. Br Med J 292:793–796.Google Scholar
23. Olmos, P, A'Hern, R, Heaton, DA, Millward, BA, Risley, D, Pyke, DA, Leslie, RDG (1988): The significance of the concordance rate for Type 1 (insulin-dependent) diabetes in identical twins. Diabetologia 31:747–750.Google Scholar
24. Srikanta, S, Ganda, OP, Jackson, RA, Gleeson, RE, Kaldany, A, Garovoy, MR, Milford, EL, Carpenter, CB, Soeldner, JS, Eisenbarth, GS (1983): Type 1 diabetes mellitus in monozygotic twins: chronic progressive β cell dysfunction. Ann Int Med 99:320–326.Google Scholar
25. Sutherland, DE, Sibley, R, Yu, X-Z. Michael, A, Srikanta, S, Taub, F, Najarian, J, Goetz, FC (1984): Twin-to-twin pancreas transplantation: reversal and re-enactment of the pathogenesis of Type 1 diabetes. Trans Assoc Am Physicians 97:80–87.Google Scholar
26. Todd, JA, Bell, JI, McDevitt, HO (1987): HLA DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329:599–604.Google Scholar
27. Tun, RYM, Peakman, M, Alviggi, L, Hussain, MJ, Lo, SSS, Shattock, M, Pyke, DA, Bottazzo, GF, Vergani, D, Leslie, RDG (1994): The importance of persistent cellular and humoral immune changes in the prediabetic period. A prospective identical twin study. Br Med J (in press).Google Scholar
28. Utz, U, Biddison, WE, McFarland, HF, McFarlin, DE, Flerlage, M, Martin, R (1993): Skewed T-cell receptor repertoire in genetically identical twins correlates with multiple sclerosis. Nature 364:243–247.Google Scholar
29. Vergani, D (1987): Cell mediated immunity. In Barnett, AH (ed): Immunogenetics of Insulin-Dependent Diabetes. Lancaster: MTP Press.Google Scholar