Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type
Hagopian, William A. ; Karlsen, Allan E. LU ; Gottsäter, Anders LU ; Landin-Olsson, Mona LU ; Grubin, Catherine E. ; Sundkvist, Göran LU ; Petersen, Jacob S. ; Boel, Esper ; Dyrberg, Thomas and Lernmark, Åke LU
(1993)
In Journal of Clinical Investigation
91(1).
p.368-374
- Abstract
At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. Our quantitative immunoprecipitation assay uses recombinant human islet GAD65 stably expressed in hamster fibroblasts. Electrophoretic mobility was identical to native islet GAD65. Like native antigen, recombinant GAD65 migrated as two bands during electrophoresis, but converted to one under stronger reduction. Immunoprecipitation was linear with respect to antibody or antigen concentration. In 120 population-based diabetic patients of all ages grouped by treatment at onset and after 18 mo,... (More)
At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. Our quantitative immunoprecipitation assay uses recombinant human islet GAD65 stably expressed in hamster fibroblasts. Electrophoretic mobility was identical to native islet GAD65. Like native antigen, recombinant GAD65 migrated as two bands during electrophoresis, but converted to one under stronger reduction. Immunoprecipitation was linear with respect to antibody or antigen concentration. In 120 population-based diabetic patients of all ages grouped by treatment at onset and after 18 mo, GAD65Ab were present in 70% on insulin (n = 37), 10% on oral agent (n = 62, P < 0.0001), 69% changing from oral agent to insulin (n = 16, P < 0.001), and 1 of 33 controls. 65% with GAD65Ab, versus 8% without, changed from oral agent to insulin (P < 0.01). The GAD65Ab quantitative index was remarkably stable, and only 2 of 32 patients changed antibody status during follow-up. Concordance between GAD65Ab and islet cell antibodies was 93%. Quantitative correlation was approximate but significant. This highly sensitive, quantitative, high capacity assay for GAD65Ab reveals treatment requirements better than clinical criteria, perhaps guiding immunomodulatory therapy.
(Less)
- author
- Hagopian, William A.
; Karlsen, Allan E.
LU
; Gottsäter, Anders
LU
; Landin-Olsson, Mona
LU
; Grubin, Catherine E.
; Sundkvist, Göran
LU
; Petersen, Jacob S.
; Boel, Esper
; Dyrberg, Thomas
and Lernmark, Åke
LU
- organization
- publishing date
- 1993-01-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Autoantigen, Autoimmunity, BHK fibroblasts, Immunoprecipitation, Islet cell antibodies
- in
- Journal of Clinical Investigation
- volume
- 91
- issue
- 1
- pages
- 7 pages
- publisher
- The American Society for Clinical Investigation
- external identifiers
-
- pmid:8423232
- scopus:0027391608
- ISSN
- 0021-9738
- DOI
- 10.1172/JCI116195
- language
- English
- LU publication?
- yes
- id
- e0557944-da3a-4f5f-b30d-2335cd7efaab
- date added to LUP
- 2019-09-11 09:27:47
- date last changed
- 2024-10-17 14:26:26
@article{e0557944-da3a-4f5f-b30d-2335cd7efaab,
abstract = {{<p>At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. Our quantitative immunoprecipitation assay uses recombinant human islet GAD65 stably expressed in hamster fibroblasts. Electrophoretic mobility was identical to native islet GAD65. Like native antigen, recombinant GAD65 migrated as two bands during electrophoresis, but converted to one under stronger reduction. Immunoprecipitation was linear with respect to antibody or antigen concentration. In 120 population-based diabetic patients of all ages grouped by treatment at onset and after 18 mo, GAD65Ab were present in 70% on insulin (n = 37), 10% on oral agent (n = 62, P < 0.0001), 69% changing from oral agent to insulin (n = 16, P < 0.001), and 1 of 33 controls. 65% with GAD65Ab, versus 8% without, changed from oral agent to insulin (P < 0.01). The GAD65Ab quantitative index was remarkably stable, and only 2 of 32 patients changed antibody status during follow-up. Concordance between GAD65Ab and islet cell antibodies was 93%. Quantitative correlation was approximate but significant. This highly sensitive, quantitative, high capacity assay for GAD65Ab reveals treatment requirements better than clinical criteria, perhaps guiding immunomodulatory therapy.</p>}},
author = {{Hagopian, William A. and Karlsen, Allan E. and Gottsäter, Anders and Landin-Olsson, Mona and Grubin, Catherine E. and Sundkvist, Göran and Petersen, Jacob S. and Boel, Esper and Dyrberg, Thomas and Lernmark, Åke}},
issn = {{0021-9738}},
keywords = {{Autoantigen; Autoimmunity; BHK fibroblasts; Immunoprecipitation; Islet cell antibodies}},
language = {{eng}},
month = {{01}},
number = {{1}},
pages = {{368--374}},
publisher = {{The American Society for Clinical Investigation}},
series = {{Journal of Clinical Investigation}},
title = {{Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type}},
url = {{http://dx.doi.org/10.1172/JCI116195}},
doi = {{10.1172/JCI116195}},
volume = {{91}},
year = {{1993}},
}