Skip to main content
Log in

Islet cell cytoplasmic antibody reactivity in midgestational human fetal pancreas

  • Originals
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

The reactivity of islet cell cytoplasmic antibodies (ICA)-positive and ICA-negative sera of recent onset type 1 diabetic patients was studied in human fetal pancreata of 12–18 weeks' gestation and compared with the reactivity of these sera in adult human control pancreata. The aims of the study were: (1) to observe the presence of ICA staining in human fetal islet cells; (2) to compare endpoint titres (in Juvenile Diabetes Foundation units) of ICA-positive patient sera in fetal pancreata and adult human control pancreata. Ten ICA-positive sera and eight ICA-negative sera from newly diagnosed diabetic patients and four sera from healthy controls were tested on three human adult and eight human fetal pancreata. As in the adult control pancreata. ICA-positive sera reacted to insulin-, glucagon-, and somatostatin-positive cells of fetal pancreata of all gestational ages. This was observed both in single cells and in cells in islet-like cell clusters. Dilution of a reference serum gave similar results in both adult and fetal pancreata. In contrast, the ICA-positive patient sera yielded a striking heterogeneity in fetal as well as in adult pancreata. However, end-point titres between adult and fetal pancreata did not differ significantly (P>0.05). In conclusion, ICA-positive sera from recent onset diabetic patients show that the expression of molecules to which ICA react is present in all islet cells and starts before week 12 of gestation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bruining GJ, Molenaar JM, Grobbee DE, Hofman A, Scheffer GJ, Bruining HA, De Bruyn AM, Valkenburg HA, Ten-year follow-up study of islet cell antibodies and childhood diabetes mellitus. Lancet: 1100–1103, 1989

  2. Atkinson MA, Kaufman DL, Newman D, Tobin AJ, MacLaren NK, Islet cell cytoplasmic autoantibody reactivity to glutamate decarboxylase in insulin-dependent diabetes. J Clin Invest 91:350–356, 1993

    Google Scholar 

  3. Greenbaum C, Palmer J, Nagataki S, Yamaguchi Y, Molenaar JL, Van Beers WAM, MacLaren NK, Lernmark Å, and participating laboratories, Improved specificity of ICA assays in the fourth international immunology of diabetes serum exchange workshop. Diabetes 41:1570–1574, 1992

    Google Scholar 

  4. Nayak RC, Omar AK, Rabizadeh A, Srikanta S, Eisenbarth GS, Cytoplasmic islet cell antibodies: evidence that the target antigen is a sialoglyco-conjugate. Diabetes 34:617–619, 1985

    Google Scholar 

  5. Colman PG, Nayak RC, Campbell IL, Eisenbarth GS, Binding of cytoplasmic islet cell antibodies is blocked by human pancreatic glycolipid extracts. Diabetes 37:645–652, 1988

    Google Scholar 

  6. Pietropaolo M, Castaño L, Babu S, Buelow R, Kuo YL, Martin S, Martin A, Powers AC, Prochazka M, Naggert J, Leiter EH, Eisenbarth GS, Islet cell autoantigen 69 kD (ICA69). Molecular cloning andcharacterization of a novel diabetes-associated autoantigen. J Clin Invest 92:359–371, 1993

    Google Scholar 

  7. Genovese S, Bonifacio E, McNally JM, Dean BM, Wagner R, Bosi E, Gale EAM, Bottazzo GF, Distinct cytplasmic islet cell antibodies with different risks for type I (insulin-dependent) diabetes mellitus. Diabetologia 35:385–388, 1992

    Google Scholar 

  8. Adams TE, Alpert S, Hanahan D, Non-tolerance and autoantibodies to a transgenic self antigen expressed in pancreatic beta cells. Nature 325:223–228, 1987

    Google Scholar 

  9. Sundkvist G, Bergqvist A, Weibull H, Bergqvist D, Fält K, Landin Olsson M, Lernmark Å, Islet cell antibody reactivity with human fetal pancreatic islets. Diabetes Res Clin Pract 14:1–8, 1991

    Google Scholar 

  10. RR Krijger de, Aanstoot HJ, Kranenburg G, Reinhard M, Visser WJ, Bruining GJ, The midgestational human fetal pancreas contains cells coexpressing islet hormones. Dev Biol 153:368–375, 1992

    Google Scholar 

  11. Bruining GJ, Molenaar J, Tuk CW, Lindeman J, Bruining HA, Marner B, Clinical time-course and characteristics of islet-cell cytoplasmic antibodies in childhood diabetes. Diabetologia 26:24–29, 1984

    Google Scholar 

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

    Google Scholar 

  13. Wilkin T, Armitage M, Casey C, Pyke DA, Hoskin PJ, Rodier M, Diaz JC, Leslie RDG, Value of insulin auto-antibodies as serum markers for insulin-dependent diabetes mellitus. Lancet I:480–482, 1985

    Google Scholar 

  14. Madsen OD, Landin-Olsson M, Bille G, Sundkvist G, Lernmark Å, Dahlqvist G, Ludvigsson J, A two-colour immunofluorescence test with a monoclonal human proinsulin antibody improves the assay for islet cell antibodies. Diabetologia 29:115–118, 1986

    Google Scholar 

  15. Landin-Olsson M, Sundkvist G, Lernmark Å, Prolonged incubation in the two-colour immunofluorescence test increases the prevalence and titre of islet cell antibodies in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30:327–332, 1987

    Google Scholar 

  16. Bottazzo GF, Doniach D, Islet-cell antibodies (ICA) in diabetes mellitus. Evidence of an autoantigen common to all cells in the islet of Langerhans. Ric Clin Lab 8:29–39, 1978

    Google Scholar 

  17. Landin-Olsson M, Sundkvist G, Lernmark Å, Precision of isletcell antibody assay depends on the pancreas. Diabetologia 31:511(A), 1988

    Google Scholar 

  18. Nayak RC, Omar MAK, Rabizadeh A, Srikanta S, Eisenbarth GS, “Cytoplasmic” islet cell antibodies: evidence that the target antigen is a sialoglycoconjugate. Diabetes 28:617–619, 1985

    Google Scholar 

  19. McCulloch DK, Barmeier H, Neifing JL, Palmer JPP, Metabolic state of the pancreas affects end-point titre in the islet cell antibody assay. Diabetologia 34:622–625, 1991

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Krijger, R.R., van Krugten, M.V., Kranenburg, G. et al. Islet cell cytoplasmic antibody reactivity in midgestational human fetal pancreas. Acta Diabetol 31, 232–235 (1994). https://doi.org/10.1007/BF00571957

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00571957

Key words

Navigation