Autoantibodies in IDDM primarily recognize the 65,000-Mr rather than the 67,000-Mr isoform of glutamic acid decarboxylase
Hagopian, William A. ; Michelsen, Birgitte ; Karlsen, Allan E. ; Larsen, Fleming ; Moody, Alistar ; Grubin, Catherine E. ; Rowe, Rachel ; Petersen, Jacob ; Mcevoy, Robert and Lernmark, Åke LU
(1993)
In Diabetes
42(4).
p.631-636
- Abstract
Glutamic acid decarboxylase autoantibodies may aid in rapid screening strategies predicting IDDM before clinical onset. Rat islets contain GAD65 and GAD67 autoantibody targets, but human islets express only GAD65, now confirmed by direct immunoprecipitation from radiolabeled rat and human islets. Because human IDDM involves β-cell-specific autoimmunity, we tested 190 new IDDM patients and 51 healthy control subjects for antibodies to recombinant human islet GAD65, rat islet GAD67, or human insulinoma/ cerebellum GAD67, each expressed separately in hamster fibroblasts. By using immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and... (More)
Glutamic acid decarboxylase autoantibodies may aid in rapid screening strategies predicting IDDM before clinical onset. Rat islets contain GAD65 and GAD67 autoantibody targets, but human islets express only GAD65, now confirmed by direct immunoprecipitation from radiolabeled rat and human islets. Because human IDDM involves β-cell-specific autoimmunity, we tested 190 new IDDM patients and 51 healthy control subjects for antibodies to recombinant human islet GAD65, rat islet GAD67, or human insulinoma/ cerebellum GAD67, each expressed separately in hamster fibroblasts. By using immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and densitometric fluorogram scanning, 132 of 190 (70%) of new IDDM patients had GAD65 autoantibodies, whereas only 17 of 190 (9%) had antibodies to rat GAD67 (P < 0.001). Of healthy control subjects, 2 of 51 (3.9%) and 1 of 51 (1.9%) had antibodies to GAD65 and GAD67, respectively. All 17 GAD67 antibody-positive patients also had GAD65 antibodies; 14 of 17 with greater GAD65 than GAD67 index. Control studies showed comparable reactivity between recombinant rat and human GAD67 and between different subcellular preparations of recombinant GAD67 of either species. In conclusion, only GAD65 is expressed in human islets, the autoantibody response is primarily to this isoform, and GAD67 antibodies add little to IDDM detection.
(Less)
- author
- Hagopian, William A.
; Michelsen, Birgitte
; Karlsen, Allan E.
; Larsen, Fleming
; Moody, Alistar
; Grubin, Catherine E.
; Rowe, Rachel
; Petersen, Jacob
; Mcevoy, Robert
and Lernmark, Åke
LU
- publishing date
- 1993-01-01
- type
- Contribution to journal
- publication status
- published
- in
- Diabetes
- volume
- 42
- issue
- 4
- pages
- 631 - 636
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- pmid:8454115
- scopus:0027450794
- ISSN
- 0012-1797
- DOI
- 10.2337/diab.42.4.631
- language
- English
- LU publication?
- no
- id
- 05998ca1-edd0-4058-a79e-9e783f800a76
- date added to LUP
- 2019-09-11 09:25:54
- date last changed
- 2024-04-02 15:46:38
@article{05998ca1-edd0-4058-a79e-9e783f800a76,
abstract = {{<p>Glutamic acid decarboxylase autoantibodies may aid in rapid screening strategies predicting IDDM before clinical onset. Rat islets contain GAD<sub>65</sub> and GAD<sub>67</sub> autoantibody targets, but human islets express only GAD<sub>65</sub>, now confirmed by direct immunoprecipitation from radiolabeled rat and human islets. Because human IDDM involves β-cell-specific autoimmunity, we tested 190 new IDDM patients and 51 healthy control subjects for antibodies to recombinant human islet GAD<sub>65</sub>, rat islet GAD<sub>67</sub>, or human insulinoma/ cerebellum GAD<sub>67</sub>, each expressed separately in hamster fibroblasts. By using immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and densitometric fluorogram scanning, 132 of 190 (70%) of new IDDM patients had GAD<sub>65</sub> autoantibodies, whereas only 17 of 190 (9%) had antibodies to rat GAD<sub>67</sub> (P < 0.001). Of healthy control subjects, 2 of 51 (3.9%) and 1 of 51 (1.9%) had antibodies to GAD<sub>65</sub> and GAD<sub>67</sub>, respectively. All 17 GAD<sub>67</sub> antibody-positive patients also had GAD<sub>65</sub> antibodies; 14 of 17 with greater GAD<sub>65</sub> than GAD<sub>67</sub> index. Control studies showed comparable reactivity between recombinant rat and human GAD<sub>67</sub> and between different subcellular preparations of recombinant GAD<sub>67</sub> of either species. In conclusion, only GAD<sub>65</sub> is expressed in human islets, the autoantibody response is primarily to this isoform, and GAD<sub>67</sub> antibodies add little to IDDM detection.</p>}},
author = {{Hagopian, William A. and Michelsen, Birgitte and Karlsen, Allan E. and Larsen, Fleming and Moody, Alistar and Grubin, Catherine E. and Rowe, Rachel and Petersen, Jacob and Mcevoy, Robert and Lernmark, Åke}},
issn = {{0012-1797}},
language = {{eng}},
month = {{01}},
number = {{4}},
pages = {{631--636}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Autoantibodies in IDDM primarily recognize the 65,000-M<sub>r</sub> rather than the 67,000-M<sub>r</sub> isoform of glutamic acid decarboxylase}},
url = {{http://dx.doi.org/10.2337/diab.42.4.631}},
doi = {{10.2337/diab.42.4.631}},
volume = {{42}},
year = {{1993}},
}