Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with Type 1 (insulin-dependent) diabetes mellitus

Summary

Antibodies to glutamic acid decarboxylase, previously known as the 64 kD antigen, appear to be more predictive of Type 1 (insulin-dependent) diabetes mellitus in Caucasoids than other autoantibodies to islet cell antigens. However, seropositivity to glutamic acid decarboxylase is not universal at the onset of Type 1 diabetes and the prevalence in Asians is low compared to Caucasoid patients. This suggests the involvement of multiple pancreatic autoantigens in the Type 1 diabetes autoimmune process or, genetic differences within and between ethnic groups that contribute to the heterogeneous autoimmune response to glutamic acid decarboxylase or both. Alternatively some cases of Type 1 diabetes could have an aetiology unrelated to autoimmunity. This study examined the differential response to glutamic acid decarboxylase according to HLA-DR and -DQ genotypes, as determined by RFLP, in 49 white Australian and 44 Asian patients with Type 1 diabetes. Among Australians heterozygous for HLA-DR3, DR4, 85% were positive for antibodies to glutamic acid decarboxylase, significantly different (p = 0.039) from the prevalence of 48% in patients with at least one HLA-DR antigen other than DR3 or DR4. Also, among Australians, the presence of “low risk” HLA-DQ antigens, namely DQw5, DQw6 or DQw7, reduced the prevalence of antibodies to glutamic acid decarboxylase by 40% (p = 0.064). Among Asians with Type 1 diabetes and with antibodies to glutamic acid decarboxylase, HLA-DR9 was significantly (p = 0.037) increased in frequency, at 63% compared with 22% in those without glutamic acid decarboxylase antibodies, and the presence of a “low risk” HLA-DQ allele reduced the antibody rates by 87% (p = 0.003). These observations may reflect differential genetic/environmental interactions in Type 1 diabetes or differential persistence of glutamic acid decarboxylase antibodies in those with different genetic backgrounds.

References

  1. 1.

    Palmer JP, Asplin CM, Clemons P et al. (1983) Insulin antibodies in insulin dependent diabetes before insulin treatment. Science 222: 1337–1339

  2. 2.

    Bottazzo GF, Florin-Christensen A, Doniach D (1974) Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet II: 1279–1282

  3. 3.

    Baekkeskov S, Landin M, Kristensen JK et al. (1987) Antibodies to a 64,000-Mr human islet cell protein precede the clinical onset of insulin-dependent diabetes. J Clin Invest 79: 926–34

  4. 4.

    Rowley MJ, Mackay IR, Chen Q-Y, Knowles WJ, Zimmet P (1992) Antibodies to glutamic acid decarboxylase discriminate major types of diabetes mellitus. Diabetes 41: 548–551

  5. 5.

    Atkinson MD, Maclaren NK, Sharp DW, Lacy PE, Riley WJ (1990) 64,000 Mr autoantibodies as predictors of insulin-dependent diabetes. Lancet 335: 1357–1360

  6. 6.

    Clare-Salzler MJ, Tobin AJ, Kaufman DL (1992) Glutamate decarboxylase: an autoantigen in IDDM. Diabetes Care 15: 132–135

  7. 7.

    Kaufman DL, Erlander MG, Clare-Salzler M, Atkinson MA, Maclaren NK, Tobin AJ (1992) Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J Clin Invest 89: 283–292

  8. 8.

    Thomson G, Robinson WP, Kutiner MK et al. (1980) Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus. Am J Hum Genet 43: 799–816

  9. 9.

    Todd JA, Bell JI, McDevitt HO (1987) HLA-DQβ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329: 599–604

  10. 10.

    Hawkins BR, Lam KSL, Ma JTC et al. (1987) Strong association of HLA-DR3/DRw9 heterozygosity with early-onset insulin-dependent diabetes meillitus in Chinese. Diabetes 36: 1297–1300

  11. 11.

    Aparicio JMR, Wakisaka A, Takada A, Matsuura N, Aizawa M (1988) HLA-DQ system and insulin-dependent diabetes mellitus in Japanese: does it contribute to the development of IDDM as it does in Caucasians? Immunogenetics 28: 240–246

  12. 12.

    Rewers M, LaPorte RE, King H, Tuomilehto J (1988) Trends in the prevalence and incidence of diabetes: insulin-dependent diabetes mellitus in childhood. World Hlth Statist Quart 41: 179–189

  13. 13.

    Tuomilehto J, Rewers M, Reunanen A et al. (1991) Increasing trend in type 1 (insulin-dependent) diabetes mellitus in childhood in Finland. Analysis of age. calendar time and birth cohort effects during 1965 to 1984. Diabetologia 34: 282–287

  14. 14.

    Gao X, Serjeantson SW (1991) Diversity in HLA-DR4-related DR,DQ haplotypes in Australia, Oceania and China. Hum Immunol 32: 269–276

  15. 15.

    Serjeantson SW, Tait BD, Chiewsilp P et al. (1986) Insulin dependent diabetes mellitus workshop: joint report. In: Aizawa M, Natori T, Wakisaka A, Konoeda Y (eds) HLA in Asia-Oceania 1986. Hokkaido University Press, Sapporo, pp 380–391

  16. 16.

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

  17. 17.

    Bakos S, Mackay IR, Rowley MJ, Knowles W, Zimmet P (1992) Islet cell antibodies and other markers of autoimmunity and diabetes mellitus in Nauruans. Diabetologia 34: 796–800

  18. 18.

    Kohonen-Corish MRJ, Serjeantson SW, Lee HK, Zimmet P (1987) Insulin-dependent diabetes mellitus: HLA-DR and -DQ genotyping in three ethnic groups. Disease Markers 5: 153–164

  19. 19.

    Bodmer JG, Marsh SGE, Albert ED et al. (1991) Nomenclature for factors of the HLA system, 1990. Hum Immunol 31: 186–194

  20. 20.

    Serjeantson SW, Easteal S (1991) Cross-ethnic group comparisons of HLA class II alleles and insulin-dependent diabetes mellitus. Balliére's Clin End Metab 5: 299–320

  21. 21.

    Neufeld M, MacLaren NK, Riley WJ et al. (1980) Islet cell and other organ-specific antibodies in U.S. Caucasians and Blacks with insulin-dependent diabetes mellitus. Diabetes 29: 589–592

  22. 22.

    Serjeantson S, Theophilus J, Zimmet P, Court JM, Crossley JR, Elliott RB (1981) Lymphocytotoxic antibodies and HLA in juvenile-onset diabetes mellitus. Diabetes 30: 26–29

  23. 23.

    Bärmeier H, Ivarsson S, Lindberg B et al. (1991) High titer 64K antibodies in 5-year follow-up study of type 1 diabetic children. Diabetologia 34 [Suppl 2]: A98 (Abstract)

  24. 24.

    Morris PJ, Vaughan H, Irvine WJ et al. (1976) HLA and pancreatic islet-cell antibodies in diabetes. Lancet II: 652–653

  25. 25.

    Irvine WJ, McCallum CJ, Gray RS et al. (1977) Pancreatic isletcell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type. Diabetes 26: 138–147

  26. 26.

    Gleichmann H, Zorcher B, Greulich B (1984) Correlation of islet cell antibodies and HLA-DR phenotypes with diabetes mellitus in adults. Diabetologia 27: 90–92

  27. 27.

    Groop L, Miettinen A, Groop P-H, Meri S, Koskimies S, Bottazzo GF (1988) Organ-specific autoimmunity and HLA-DR antigens as markers for β-cell destruction in patients with type II diabetes. Diabetes 37: 99–103

  28. 28.

    Mimura G, Kida K, Matsuura N et al. (1990) Immunogenetics of early-onset insulin-dependent diabetes mellitus among the Japanese: HLA, Gm, BF, GLO, and organ-specific autoantibodies — the JDS study. Diabetes Res Clin Prac 8: 253–262

  29. 29.

    Palmer JP, McCulloch DK (1991) Prediction and prevention of IDDM, 1991. Diabetes 40: 943–947

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Serjeantson, S.W., Kohonen-Corish, M.R.J., Rowley, M.J. et al. Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35, 996–1001 (1992). https://doi.org/10.1007/BF00401432

Download citation

Key words

  • Glutamic acid decarboxylase
  • Type 1 (insulin-dependent) diabetes mellitus
  • HLA-DR
  • HLA-DQ
  • Hong Kong
  • Korea
  • Japan