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Congenital rubella syndrome as a model for Type 1 (insulin-dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies


An increased prevalence of Type 1 (insulin-dependent) diabetes has been reported in patients with congenital rubella. Rubella virus multiplies in the pancreas, and we have hypothesized that studies of children with congenital rubella would be of great importance in following the development of Type 1 diabetes in a defined, susceptible population. Two hundred and forty-one children with congenital rubella (mean age 17.4±0.3 years; 65% black and hispanic) have been evaluated, 30 of whom already have diabetes and 17 of whom have borderline glucose tolerance. In these latter two groups, HLA-DR3 is significantly increased and HLA-DR2 significantly decreased. Pancreatic islet cell cytotoxic surface antibodies are found in 20% of the total congenital rubella population, including in more than 50% in the time period before they develop diabetes and are not related to any specific HLA type. In addition, anti-microsomal and anti-thyroglobulin antibodies are found in 34% of this population. The data demonstrate that Type 1 diabetes developing in congenital rubella patients has the genetic and immunological features of classical Type 1 diabetes, namely the presence of HLA-DR3, the absence of HLA-DR2, islet cell surface antibodies before decompensation and an increased prevalence of anti-thyroid antibodies. Patients with non-diabetic congenital rubella represent an easily identifiable group in whom other immunological factors associated with Type 1 diabetes can be elucidated and possibly modified.


  1. 1.

    Hay DR (1949) The relation of maternal rubella to congenital deafness and other abnormalities in New Zealand. NZ Med J 48: 604–608

  2. 2.

    Menser MA, Forrest JM, Honeyman MC, Burgess JA (1974) Diabetes, HLA-antigens and congenital rubella. Lancet 2: 1508–1509

  3. 3.

    Shaver KA, Boughman JA, Lovinger RD, Monhanakumar T, Nance WE (1982) Glucose intolerance and HLA antigens in the congenital rubella syndrome. Diabetes 31 (Suppl 2): 97 A

  4. 4.

    Naeye RL, Blanc W (1965) Pathogenesis of congenital rubella. JAMA 194: 109–115

  5. 5.

    Rayfield EJ, Seto Y (1978) Viruses and the pathogenesis of diabetes mellitus. Diabetes 27:1126–1140

  6. 6.

    National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1057

  7. 7.

    Ginsberg-Fellner F, Dobersen MJ, Witt ME, Rayfield EJ, Rubinstein P, Notkins AL (1982) HLA antigens, cytoplasmic islet cell antibodies and carbohydrate tolerance in families of children with insulin-dependent diabetes mellitus. Diabetes 31: 292–298

  8. 8.

    Martel JL, Jaramillo S, Allen FH Jr, Rubinstin P (1974) Serology for automated cytotoxicity assay: contrast fluorescence test. Vox Sang 27: 13–20

  9. 9.

    Van Rood JJ, Van Leeuwen A, Ploehm SS (1976) Simultaneous detection of two cell populations by two-colour fluorescence and application to the recognition of B-cell determinants. Nature 262: 795–797

  10. 10.

    Toguchi Y, Ginsberg-Fellner F, Rubinstein P (1983) Islet cell surface antibodies (ICSA) in patients with insulin-dependent diabetes and their first degree relatives: a study of 112 families. Diabetes 32 (Suppl 1):150A

  11. 11.

    Dobersen MJ, Scharff JE, Ginsberg-Fellner F, Notkins AL (1980) Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus. N Engl J Med 303: 1493–1498

  12. 12.

    Roman SH, Kovn F, Davies TF (1984) Enzyme-linked immuno-sorbent microassay and hemagglutination compared for detection of thyroglobulin and thyroid microsomal autoantibodies. Clin Chem 30: 246–250

  13. 13.

    Svejgaard A, Platz R, Ryder LP (1980) Insulin-dependent diabetes mellitus (Joint Report). In: Terasaki PI (ed) Histocompatability testing 1980. UCLA Tissue Typing Laboratory, Los Angeles, pp 638–656

  14. 14.

    Rubinstein P, Walker ME, Fedun B, Witt ME, Cooper LZ, Ginsberg-Fellner F (1982) The HLA system in congenital rubella patients with and without diabetes. Diabetes 31: 1088–1091

  15. 15.

    Bright GM, Clarke W, Kaiser D, Shaver K, Nance W (1982) Islet cell and other endocrine autoantibodies in congenital rubella. Diabetes 31 (Suppl 2): 101A

  16. 16.

    Kyllo CJ, Nuttall FQ (1978) Prevalence of diabetes mellitus in school-age children in Minnesota. Diabetes 27: 57–60

  17. 17.

    Rubinstein P, Ginsberg-Fellner F, Falk C (1981) Genetics of Type 1 diabetes mellitus: a single recessive predisposition gene mapping between HLA-B and GLO. Am J Hum Genet 33: 865–882

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Ginsberg-Fellner, F., Witt, M.E., Yagihashi, S. et al. Congenital rubella syndrome as a model for Type 1 (insulin-dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies. Diabetologia 27, 87–89 (1984).

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Key words

  • Type 1 diabetes
  • congenital rubella
  • islet cell surface antibodies
  • viral trigger