, Volume 38, Issue 7, pp 816–822 | Cite as

Islet autoantibody markers in IDDM: risk assessment strategies yielding high sensitivity

  • E. Bonifacio
  • S. Genovese
  • S. Braghi
  • E. Bazzigaluppi
  • Y. Lampasona
  • P. J. Bingley
  • L. Rogge
  • M. R. Pastore
  • E. Bognetti
  • G. F. Bottazzo
  • E. A. M. Gale
  • E. Bosi


Identification of islet autoantigens offers the possibility that antibody tests other than islet cell antibodies may be used for assessing risk of insulin-dependent diabetes mellitus (IDDM). The aim of this study was to determine the combination of islet autoantibody markers that could identify most future cases of IDDM. Islet cell antibodies, antibodies to glutamic acid decarboxylase (GAD)65, 37,000/ 40,000 Mr islet tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. Islet cell antibodies were detected in 88 % of IDDM patients and 81 % with pre-IDDM, GAD65 antibodies in 70 % of IDDM patients and 89 % with pre-IDDM, and antibodies to 37,000/40,000 Mr islet tryptic fragments in 54 % of IDDM patients and in 48 % with pre-IDDM. The latter were found only in conjunction with islet cell antibodies and were more frequent in young onset cases. All 20 IDDM patients and the 3 pre-IDDM subjects who had islet cell antibodies without GAD65 antibodies had antibodies to 37,000/40,000 Mr islet tryptic fragments, and all but one had disease onset before age 15 years. No sera strongly immunoprecipitated in vitro translated ICA69 or carboxypeptidase-H; 4 % of patients had anti-ICA69 and 11 % anti-carboxypeptidase-H levels above those of the control subjects. The findings suggest that none of the single antibody specificities are as sensitive as islet cell antibodies, but that a combination of GAD65 antibodies and antibodies to 37,000/40,000 Mr islet tryptic fragments has the potential to identify more than 90 % of future cases of IDDM. Such a strategy could eventually replace islet cell antibodies in population screening for IDDM risk assessment.

Key words

Islet cell antibodies glutamic acid decarboxylase65 antibodies islet autoantigens insulin-dependent diabetes mellitus prediction carboxypeptidase-H ICA69. 



Confidence limits




glutamic acid decarboxylase


glutamic acid decarboxylase65 antibodies


insulin autoantibodies


islet cell antibodies


insulin-dependent diabetes mellitus

JDF units

Juvenile Foundation Diabetes units


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • E. Bonifacio
    • 1
  • S. Genovese
    • 1
  • S. Braghi
    • 1
  • E. Bazzigaluppi
    • 1
  • Y. Lampasona
    • 1
  • P. J. Bingley
    • 2
  • L. Rogge
    • 3
  • M. R. Pastore
    • 1
  • E. Bognetti
    • 1
  • G. F. Bottazzo
    • 4
  • E. A. M. Gale
    • 2
  • E. Bosi
    • 1
  1. 1.Istituto Scientifico San RaffaeleUniversity of MilanMilanItaly
  2. 2.Department of Diabetes and MetabolismSt Bartholomew’s Hospital Medical CollegeLondonUK
  3. 3.Roche Milano RicercheMilanItaly
  4. 4.Department of ImmunologyLondon Hospital Medical CollegeLondonUK

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