Acta Diabetologica

, Volume 28, Issue 3–4, pp 229–232 | Cite as

HLA antigens in Italian type 1 diabetic patients: role of DR3/DR4 antigens and breast feeding in the onset of the disease

  • E. Bognetti
  • F. Meschi
  • C. Malavasi
  • M. R. Pastore
  • A. Sergi
  • M. T. Illeni
  • C. Maffeis
  • L. Pinelli
  • G. Chiumello
Originals

Abstract

HLA-A, B, C, DR and DQ typing was performed in 381 Italian insulin-dependent diabetic patients and in 905 normal Italian subjects. The diabetic patients had significantly higher frequencies of HLA-Cw7, B8, B18, DR3, DR4, DQw2 and DQw3 and significantly lower frequencies of HLA-B17, Bw51, DR2, DR7 and DRw11. The frequency of heterozygosity for HLA-DR3/DR4 was significantly higher in patients who developed the disease in the first 2 years of life and DR3+/DR4-, DQw2 and DQw3 alleles were higher in those aged less than 14 years at onset. The HLA-DR4 allele was associated with onset of diabetes in autumn and HLA-B18 with onset in Autumn-winter. Diabetic children who were breast fed had a later onset of insulin-dependent diabetes mellitus than those who were bottle fed but these differences were independent of HLA typing (11.18±0.72 years vs 9.23±0.42 years; mean±SEM). We conclude that: (1) in general, HLA distribution in Italian insulin-dependent diabetic patients reflects previous data reported in other European and North American populations; (2) HLA-DR3 and DR4 are strongly associated with insulin-dependent diabetes in Italy as well, and these alleles seem to predispose to an earlier onset of the disease; and (3) breast feeding may delay the onset of the disease.

Key words

HLA Insulin-dependent diabetes mellitus Breast feeding Childhood 

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References

  1. 1.
    Rimon DI, Rotter JI, The genetics of diabetes mellitus. In: Andreani D, Di Mario U, Federlin KF, Heding LG (eds) Immunology in diabetes. Kimpton, London, pp 45–62, 1984Google Scholar
  2. 2.
    Wolf E, Spencer KM, Cudworth AG, The genetic susceptibility to type I (insulin-dependent) diabetes: analysis of HLA-DR association. Diabetologia 24:224–230, 1983Google Scholar
  3. 3.
    Nerup J, Christy M, Patz P, Ryder LP, Svejgaard A, Aspects of the genetic of insulin-dependent diabetes mellitus. In: Andreani D, Di Mario U, Federlin KF, Heding LG (eds) Immunology in diabetes. Kimpton, London, pp 63–70, 1984Google Scholar
  4. 4.
    Svejgaard A, Platz P, Ryder LP, Insulin dependent diabetes mellitus — joint results of the 8th Workshop study. In: Terasaki PI (ed) Histocompatibility testing. University of California Press, Berekely, pp 638–656, 1980Google Scholar
  5. 5.
    Murphy CC, Acton RT, Barger BO, Rodney CPG, Kirk KA, Reitnauer PJ, Roseman JM, Population genetic analysis of insulin-dependent diabetes mellitus using HLA allele frequencies. Clin Genet 23:405–414, 1983.Google Scholar
  6. 6.
    Vela M, Adorno D, Longo A, Papola F, Maccarone D, Centis D, Raponi MP, Candela A, Campea L, Orsini M, Ferrata GB, HLA typing data on 100 type I (insulin-dependent) diabetic patients from central Italy show a negative association with DR5 rather than with DR2. Clin Immunol Immunopathol 45:143–146, 1987Google Scholar
  7. 7.
    Bottazzo GF, Dean BM, McNally JM, Mackay EH, Swift PGF, Gamble DR, In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 313:353–360, 1985Google Scholar
  8. 8.
    Bottazzo GF, Death of a beta cells: homicide or suicide? Diabetic Med 3:119–130, 1986Google Scholar
  9. 9.
    Henson V, MacLaren N, Winter E, Riley W, Rotter J, Wakeland EK, Molecular genetics of insulin-dependent diabetes mellitus. Mol Biol Med 3:129–136, 1986Google Scholar
  10. 10.
    Todd JA, Bell JI, McDevitt HO, HLA-DQ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329:1599–1604, 1987Google Scholar
  11. 11.
    Ludvigsson J, Samuelsson U, Beauforts C, Deschamps I, Dorchy H, Drash A, Francois R, Herz G, New M, Shober E, HLA-DR3 is associated with a more slowly progressive form of type I (insulin-dependent) diabetes. Diabetologa 29:207–210, 1986Google Scholar
  12. 12.
    Borch-Johnsen K, Joner J, Mandrup-Poulsen T, Zachau-Christiansen B, Christy M, Kastrup K, Nerup J, Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus: a hypothesis. Lancet II:1083–1086, 1984Google Scholar
  13. 13.
    Blom L, Dahlquist G, Nystrom L, Sandstrom A, Wall S, The Swedish childhood diabetes study — social and perinatal determinants for diabetes in childhood. Diabetologia 32:7–13, 1989Google Scholar
  14. 14.
    Mittal K, Standardization of the HLA typing method and reagents. Vox Sang 34:58–63, 1968Google Scholar
  15. 15.
    Madsen M, Johnsen HE, Kissmeyer-Nielsen F, Separation of human T and B lymphocytes using AET-treated sheep red blood cells. Transplant Proc 11:1381, 1979Google Scholar
  16. 16.
    Woolf B, On estimating the relation between blood group and disease. Ann Hum Genet 19:251–253, 1955Google Scholar
  17. 17.
    Pagano GF, Cavallo Perin P, Cavalit F, Dall'Omo AM, Masciola P, Suriani R, Amoroso A, Curtoni SE, Borelli L, Lenti GF, Genetic, immunologic and environmental heterogeneity of IDDM. Incidence and 12-month follow-up of an Italian population. Diabetes 36:859–863, 1987Google Scholar
  18. 18.
    Sholz S, Alberti E, HLA and diseases: involvement of more than one HLA-linked determinant of disease susceptibility. Immunol Rev 70:78–88, 1983Google Scholar
  19. 19.
    Eberhardt MS, Wagener DK, Orchard TJ, LaPorte RE, Cavender DE, Rabin BS, Atchinson RW, Kuller LH, Drash AL, Becker DJ, HLA heterogeneity of insulin-dependent diabetes mellitus at diagnosis. The Pittsburg IDDM study. Diabetes 34:1247–1252, 1985Google Scholar
  20. 20.
    Knip M, Ilonen J, Mustonen A, Akerblom HK, Evidence of an accelerated B-cell destruction in HLA-Dw3/Dw4 heterozygous children with type I (insulin-dependent) diabetes. Diabetologia 29:347–351, 1986Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • E. Bognetti
    • 1
  • F. Meschi
    • 1
  • C. Malavasi
    • 1
  • M. R. Pastore
    • 2
  • A. Sergi
    • 2
  • M. T. Illeni
    • 3
  • C. Maffeis
    • 4
  • L. Pinelli
    • 4
  • G. Chiumello
    • 1
  1. 1.Department of Paediatrics, Endocrine Unit, San Raffaele Scientific InstituteUniversity of MilanMilanItaly
  2. 2.Department of Internal Medicine, San Raffaele Scientific InstituteUniversity of MilanMilanItaly
  3. 3.Department of ImmunohaematologyIstituto Nazionale dei TumoriMilanItaly
  4. 4.Department of PaediatricsUniversity of VeronaVeronaItaly

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