A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM
(1994) In Diabetologia 37(4). p.344-350- Abstract
Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n=10) and control (n=50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p<0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in... (More)
Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n=10) and control (n=50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p<0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0-14 year-old patients (n=105), and matched, healthy control subjects (n=157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77% and the specificity 92% compared with 8% and 98%, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methioninelabelled recombinant GAD.
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- author
- Grubin, C. E. ; Daniels, T. ; Toivola, B. ; Landin-Olsson, M. LU ; Hagopian, W. A. ; Li, L. ; Karlsen, A. E. ; Boel, E. ; Michelsen, B. and Lernmark, Å LU
- organization
- publishing date
- 1994-04-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- autoimmunity, diabetes mellitus, diagnostic accuracy, Glutamic acid decarboxylase, islet cell antibodies, receiver-operating characteristic plot
- in
- Diabetologia
- volume
- 37
- issue
- 4
- pages
- 344 - 350
- publisher
- Springer
- external identifiers
-
- scopus:0028258006
- pmid:8063033
- ISSN
- 0012-186X
- DOI
- 10.1007/BF00408469
- language
- English
- LU publication?
- yes
- id
- 08363607-a6e7-46d2-9004-8f165f58070e
- date added to LUP
- 2019-09-11 09:06:17
- date last changed
- 2024-06-13 03:16:47
@article{08363607-a6e7-46d2-9004-8f165f58070e, abstract = {{<p>Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n=10) and control (n=50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant <sup>35</sup>S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p<0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0-14 year-old patients (n=105), and matched, healthy control subjects (n=157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77% and the specificity 92% compared with 8% and 98%, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized <sup>35</sup>S-methioninelabelled recombinant GAD.</p>}}, author = {{Grubin, C. E. and Daniels, T. and Toivola, B. and Landin-Olsson, M. and Hagopian, W. A. and Li, L. and Karlsen, A. E. and Boel, E. and Michelsen, B. and Lernmark, Å}}, issn = {{0012-186X}}, keywords = {{autoimmunity; diabetes mellitus; diagnostic accuracy; Glutamic acid decarboxylase; islet cell antibodies; receiver-operating characteristic plot}}, language = {{eng}}, month = {{04}}, number = {{4}}, pages = {{344--350}}, publisher = {{Springer}}, series = {{Diabetologia}}, title = {{A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM}}, url = {{http://dx.doi.org/10.1007/BF00408469}}, doi = {{10.1007/BF00408469}}, volume = {{37}}, year = {{1994}}, }