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Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus

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Summary

The presence of cytoplasmatic islet cell antibodies (ICA) and IgG insulin autoantibodies (IgG-IAA) has been observed in the prediabetic state of type 1 (insulin-dependent) diabetes (IDDM). We therefore analyzed the prevalence of these markers in sera from 1117 healthy HLA-typed first-degree relatives (1° Rel) of IDDM patients. ICA was determined by indirect immunofluorescence on cryostat sections of human pancreas. For IgG-IAA measurement a competitive solid-phase ELISA was used. ICA were present in 3.5% of 1° Rel vs 0.4% of controls (P<0.025). The highest frequencies of ICA were found in individuals of IDDM multiplex families (7.7%) and HLA-DR1,3 (5.4%), -DR1,4 (5.8%), and -DR3,4 (6.7%) positive subjects. We therefore conclude that the prevalence of ICA is increased in 1° Rel with high genetic risk for diabetes. IgG-IAA occurred in 9.9% of 1° Rel vs 1.4% of controls (P<0.01). Like ICA, IgG-IAA were significantly increased in a group of subjects being positive for either HLA-DR1,3-DR1,4, or -DR3,4 (16.5%,P<0.01). In multiplex families, however, prevalence of IgG-IAA was not increased. In contrast to ICA there was an additional influence of age and sex: IgG-IAA were found more often in siblings (mean age, 16.6 years; prevalence, 15.0%) than in parents (mean age, 44.1 years; prevalence, 8.3%) of IDDM patients (P<0.01). In brothers the prevalence of IgG-IAA is higher than in other 1° Rel. Only a weak association between ICA and IgG-IAA was observed in subjects (n=810) tested for both antibodies. IgG-IAA occurred in 6/35 (17%) ICA positive 1°Rel, while ICA were found in 6/79 (8%) IgG-IAA positive relatives.

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Abbreviations

ICA:

islet cell antibodies

IgG-IAA:

immunoglobulin G-insulin autoantibodies

IDDM:

type 1 (insulin-dependent) diabetes mellitus

1° Rel:

first-degree relatives

JDF:

Juvenile Diabetes Foundation

WHO:

World Health Organization

ΔOD:

delta optical density

References

  1. Atkinson MA, Maclaren NK, Riley WJ, Winter WE, Fisk DD, Spillar RP (1986) Are insulin autoantibodies markers for insulin-dependent diabetes mellitus? Diabetes 35:894–898

    Google Scholar 

  2. Becker F, Schneider-Waterberg I, Walter U, Seggewiss C, Sauer H, Helmke K, Federlin K (1987) Inselzell-antikörper (ICA) und Insulinautoantikörper (IAA) bei Typ I-Diabetikern und ihren Familienmitgliedern, IDDM-Erstmanifestation und normalen Kontrollpersonen. Akt Endokrin Stoffw 8:69 (Abstract)

    Google Scholar 

  3. Bottazzo GF, Florin-Christensen A, Doniach D (1974) Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet II:1279–1283

    Google Scholar 

  4. Dean BM, Becker F, McNally JM, Tarn AC, Schwartz G, Gale EAM, Bottazzo GF (1986) Insulin autoantibodies in the pre-clinic period: correlation with islet cell antibodies and development of diabetes. Diabetologia 29:339–342

    Google Scholar 

  5. Diaz JL, Wilkin T (1986) Comparison of liquid phase radio-binding assay and solid phase ELISA for the measurement of insulin antibodies and insulin autoantibodies in serum. Diabetic Med 3:316–321

    Google Scholar 

  6. Eisenbarth GS (1986) Type I diabetes mellitus. A chronic autoimmune disease. New Engl J Med 314:1360–1368

    Google Scholar 

  7. Field LL, Fothergill-Pane C, Bertrams J, Baur MP (1986) HLA-DR effects in a large German data set. Genet Epidemiol [Suppl 1]:323–328

    Google Scholar 

  8. Gleichmann H, Bottazzo GF (1987) Progress towards standardization of cytoplasmatic islet cell-antibody assay. Diabetes 36:578–584

    Google Scholar 

  9. Gorsuch AN, Spencer MK, Lister J, Wolf E, Bottazzo GF, Cudworth AG (1982) Can future type I diabetes be predicted? A study in families of affected children. Diabetes 31:862–866

    Google Scholar 

  10. Irvine WJ, Gray RS, McCallum CJ (1976) Pancreatic islet cell antibody as a marker for asymptomatic and latent diabetes and prediabetes. Lancet II:1097–1102

    Google Scholar 

  11. Kissmeyer-Nielsen F, Kjerbye KF (1967) Lymphocytotoxic microtechnique. Purification of lymphocytes by flotation. In: Curtoni ES, Mattiuz PC, Tosi RM (eds) Histocompatibility testing. Munskaard, Copenhagen, pp 381–383

    Google Scholar 

  12. Kolb H, Krügener G, Gries FA, Bellmann O (1983) Islet cell antibodies: which method? Lancet I:479 (Letter)

    Google Scholar 

  13. Kuglin B, Burkart V, Kolb H (1987) A new competitive enzyme-linked immunosorbent assay (ELISA) for insulin autoantibodies (IAA). Diabetes [Suppl 1] 36:172A (Abstract)

  14. Kuglin B, Gries FA, Kolb H (1988) Evidence of IgG autoantibodies against human proinsulin in patients with IDDM before insulin treatment. Diabetes 37:130–133

    Google Scholar 

  15. Palmer JP (1987) Insulin autoantibodies: their role in the pathogenesis of IDDM. Diabetes/Metabol Rev 3:1005–1015

    Google Scholar 

  16. Palmer JP, Asplin CM, Clemons P, Lyen K, Tatpati O, Raghu PK, Paquette TL (1983) Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 222:1337–1339

    Google Scholar 

  17. Pilcher C, Elliott RB (1984) Improved sensitivity of islet cell cytoplasmatic antibody assay in diabetics. Lancet I:1352 (Letter)

    Google Scholar 

  18. Platz P, Jakobsen BK, Morling N, Ryder LP, Svejgaard A, Thomsen M, Christy M, Kromann H, Benn J, Nerup J, Green A, Hauge M (1981) HLA-D and DR antigens in genetic analysis of insulin-dependent diabetes mellitus. Diabetologia 21:108–115

    Google Scholar 

  19. Riley W, Krischer J, Clarke D, Malone J, Rotter J, Shah S, Vadheim C (1987) Islet cell antibodies (ICA): relative risk (RR) of developing insulin dependent diabetes (IDD) is 166! Diabetes [Suppl 1] 36:70A (Abstract)

  20. Srikanta S, Ganda OP, Rabizadeh A, Soeldner JS, Eisenbarth GS (1985) First degree relatives of patients with type I diabetes mellitus: islet-cell antibodies and abnormal insulin secretion. N Engl J Med 313:461–464

    Google Scholar 

  21. Tarn AC, Thomas JM, Howard W, Ingram D, Gale EAM (1987) 9 years follow-up in a family study: the risks for insulin dependent diabetes (IDDM). Diabetes [Suppl 1] 36:72A (Abstract)

  22. Vardi P, Dib SA, Tuttleman M, Connelly JE, Grinbergs M, Radizabeh A, Riley WJ, Maclaren NK, Eisenbarth GS, Soeldner JS (1987) Competitive insulin autoantibody assay. Prospective evaluation of subjects at high risk for development of type I diabetes mellitus. Diabetes 36:1286–1291

    Google Scholar 

  23. WHO Study Group: Diabetes Mellitus (1985). WHO Technical Report Series 727, Geneva

  24. Wilkin T, Palmer JP, Bonifacio E, Diaz JL, Kruse V (1987) First international workshop on the standardization of insulin autoantibodies (IAA). Diabetologia 30:676–677

    Google Scholar 

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Kuglin, B., Bertrams, J., Linke, C. et al. Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus. Klin Wochenschr 67, 66–73 (1989). https://doi.org/10.1007/BF01735654

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  • DOI: https://doi.org/10.1007/BF01735654

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