Journal of Neurology

, Volume 253, Issue 5, pp 636–639 | Cite as

Multiple sclerosis and autoimmune diseases

Epidemiology and HLA–DR association in North–east Italy
  • A. Laroni
  • M. Calabrese
  • P. Perini
  • M. P. Albergoni
  • F. Ranzato
  • M. Tiberio
  • L. Battistin
  • P. Gallo


An autoimmune background is thought to characterize the families of multiple sclerosis (MS) patients, but disease patterns and HLA–DR association seem to vary considerably among different ethnic groups. We investigated the prevalence of autoimmune diseases in 245 MS patients and 245 age– and sex–matched normal controls (NC), originating from and living in North–east Italy, and their first degree relatives, using a case–control method. Further, HLA–DRB1 expression was analysed in MS and NC. The following significant findings were observed: 1) a significant excess of autoimmunity in firstdegree relatives of MS patients (p = 0.000), 2) an association of MS with Type 1 diabetes mellitus (T1DM) (p = 0.02), 3) an increase in DR4 expression (namely DRB1*0401) in MS patients from families with multiple autoimmune pathology compared with reference MS patients (p=0.02) and NC (p=0.01).We conclude that the risk of autoimmune disease is higher in first–degree relatives of MS patients and that disease association and HLA–DR expression in North–east Italy differs from other geographic regions of Europe.

Key words

multiple sclerosis autoimmune disease epidemiology HLA–DR 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Broadley SA, Deans J, Sawcer SJ, Clayton D, Compston DAS (2000) Autoimmune disease in first–degree relatives of patients with multiple sclerosis. A UK survey. Brain 123:1102–1111PubMedCrossRefGoogle Scholar
  2. 2.
    Henderson RD, Bain CJ, Pender MP, et al. (2000) The occurrence of autoimmune diseases in patients with multiple sclerosis and their families. J Clin Neurosci 7:434–437PubMedCrossRefGoogle Scholar
  3. 3.
    Heinzlef O, Alamowitch S, Sazdovitch V, et al. (2000) Autoimmune diseases in families of French patients with multiple sclerosis. Acta Neurol Scand 101:36–40PubMedCrossRefGoogle Scholar
  4. 4.
    Marrosu MG, Cocco E, Lai M, Spinicci G, Pischedda MP, Contu P (2002) Patients with multiple sclerosis and risk of type 1 diabetes mellitus in Sardinia, Italy: a cohort study. Lancet 359:1461–1465PubMedCrossRefGoogle Scholar
  5. 5.
    Alter M, Sawyer GT, Latham K (1970) The frequency of diabetes mellitus in families of patients with multiple sclerosis. Neurology 20:619–621PubMedGoogle Scholar
  6. 6.
    Midgard R, Gronning M, Riise T, et al. (1996) Multiple sclerosis and chronic inflammatory diseases. A case–control study. Acta Neurol Scand 93:322–328PubMedCrossRefGoogle Scholar
  7. 7.
    Karni A, Abramsky O (1999) Association of MS with thyroid disorders. Neurology 53:883–885PubMedGoogle Scholar
  8. 8.
    Niederwieser G, Buchinger W, Bopnelli RM, et al. (2003) Prevalence of autoimmune thyroiditis and non–immune thyroid disease in multiple sclerosis. J Neurol 250:672–675PubMedCrossRefGoogle Scholar
  9. 9.
    Zanelli E, Breedveld FC, de Vries RRP (2000) HLA association with autoimmune disease: a failure to protect? Rheumatology 39:1060–1066PubMedCrossRefGoogle Scholar
  10. 10.
    Marrosu MG, Murru R, Murru MR, et al. (2001) Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia. Hum Mol Genet 10:2907–2916PubMedCrossRefGoogle Scholar
  11. 11.
    Barcellos LF, Oksenberg JR, Begovich AB, et al. (2003) HLA–DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. Am J Hum Genet 72:710–716PubMedCrossRefGoogle Scholar
  12. 12.
    Marrosu MG, Murru MR, Costa G, et al. (1997) Multiple Sclerosis in Sardinia is associated and in linkage disequilibrium with HLA–DR3 and DR4 alleles. Am J Hum Genet 61:454–457PubMedGoogle Scholar
  13. 13.
    Olerup O, Hillert J (1991) HLA class II–associated genetic susceptibility in multiple sclerosis: a critical evaluation. Tissue Antigens 38:1–15PubMedCrossRefGoogle Scholar
  14. 14.
    Ranzato F, Perini P, Tzintzeva E, et al. (2003) Increasing Frequency of Multiple Sclerosis in Padova, Italy. A 30 year epidemiological survey. Mult Scler 9:387–392PubMedCrossRefGoogle Scholar
  15. 15.
    Poser CM, Paty DW, Scheinberg L, et al. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231PubMedCrossRefGoogle Scholar
  16. 16.
    Colin MH, Daniels GH (1996) Chronic autoimmune thyroiditis. N Engl J Med 335:99–107CrossRefGoogle Scholar
  17. 17.
    Cimmino MA, Parisi M, Moggiana G, Mela GS, Accardo S (1998) Prevalence of rheumatoid arthritis in Italy: the Chiavari Study. Ann Rheum Dis 57:315–318PubMedCrossRefGoogle Scholar
  18. 18.
    Passa P (2002) Diabetes trend in Europe. Diabetes Metab Res Rev 18:S3–S8PubMedCrossRefGoogle Scholar
  19. 19.
    Bennucci M, Li Gobbi F, Del Rosso A, Manfredi M (2005) Systemic lupus erythematous: the first: the first Italian prevalence study. Reumatism 57:103–108Google Scholar
  20. 20.
    Coles A, Wing M, Smith S, et al. (1999) Pulsed monoclonal antibody treatment modulates T cell responses in multiple sclerosis but induces autoimmune thyroid disease. Lancet 354:1691–1695PubMedCrossRefGoogle Scholar
  21. 21.
    Cucca F, Todd JA (1996) HLA susceptibility to type 1 diabetes: methods and mechanisms. In: Browning MJ, McMichaels AJ, (eds) HLA/MHC: gene, molecules and function. Oxford BIOS Scientific Publishers, pp 383–406Google Scholar
  22. 22.
    Marrosu MG, Cocco E, Lai M, et al. (2002) Patients with multiple sclerosis and risk of type 1 diabetes mellitus in Sardinia, Italy: a cohort study. Lancet 359:1461–1465PubMedCrossRefGoogle Scholar
  23. 23.
    Marrosu MG, Murru MR, Costa G, et al. (1998) DRB1–DQA1–DQB1 loci and multiple sclerosis predisposition in the sardinian population. Hum Mol Genet 7:1235–1237PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  • A. Laroni
    • 3
  • M. Calabrese
    • 3
  • P. Perini
    • 3
  • M. P. Albergoni
    • 1
  • F. Ranzato
    • 3
  • M. Tiberio
    • 3
  • L. Battistin
    • 2
    • 3
  • P. Gallo
    • 3
  1. 1.Blood and Tissue BankUniversity Hospital of PadovaPadovaItaly
  2. 2.IRCCS San CamilloVenice LidoItaly
  3. 3.Multiple Sclerosis Centre of the Veneto, Region, First Neurology Clinic—Dept. of NeurosciencesUniversity of PadovaPadovaItaly

Personalised recommendations