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Recombinant Fabs of...
Recombinant Fabs of human monoclonal antibodies specific to the middle epitope of GAD65 inhibit type 1 diabetes-specific GAD65Abs
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Padoa, CJ (författare)
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Banga, JP (författare)
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Madec, AM (författare)
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Ziegler, M (författare)
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Schlosser, M (författare)
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- Ortqvist, E (författare)
- Karolinska Institutet
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- Kockum, I (författare)
- Karolinska Institutet
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Palmer, J (författare)
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Rolandsson, O (författare)
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Binder, KA (författare)
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Foote, J (författare)
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Luo, D (författare)
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Hampe, CS (författare)
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(creator_code:org_t)
- American Diabetes Association, 2003
- 2003
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:11, s. 2689-2695
- Relaterad länk:
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http://kipublication...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- Autoantibodies to the 65-kDa isoform of GAD (GAD65Abs) are associated with type 1 diabetes development, but the conformational nature of the GAD65Ab epitopes complicates the evaluation of disease risk. Six GAD65-specific recombinant Fabs (rFabs) were cloned from monoclonal antibodies b96.11, DP-C, DP-A, DPD, 144, and 221–442. The binding of GAD65Abs in 61 type 1 diabetic patients to GAD65 was analyzed by competitive radioimmunoassays with the six rFabs to ascertain disease-specific GAD65Ab binding specificities. The median binding was reduced significantly by rFab b96.11 (72%) (P < 0.0001), DP-A (84%) (P < 0.0001), DP-C (84%) (P < 0.0001), 221–442 (79%) (P < 0.0001), and DP-D (80%) (P < 0.0001). The competition pattern in type 1 diabetic patients differed from that in GAD65Ab-positive late autoimmune diabetes in adults (LADA) patients (n = 44), first-degree relatives (n = 38), and healthy individuals (n = 14). Whereas 87 and 72% of the type 1 diabetic sera were competed by rFab b96.11 and DP-C, respectively, only 34 and 26% of LADA patients, 18 and 25% of first-degree relatives, and 7 and 28% of healthy individuals showed competition (P < 0.0001). These findings support the view that type 1 diabetes is associated with disease- and epitope-specific GAD65Abs and supports the notion that the middle epitope is disease associated. These GAD65-specific rFabs should prove useful in predicting type 1 diabetes and in the study of conformational GAD65Ab epitopes.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
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Diabetes
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- Av författaren/redakt...
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Padoa, CJ
-
Banga, JP
-
Madec, AM
-
Ziegler, M
-
Schlosser, M
-
Ortqvist, E
-
visa fler...
-
Kockum, I
-
Palmer, J
-
Rolandsson, O
-
Binder, KA
-
Foote, J
-
Luo, D
-
Hampe, CS
-
visa färre...
- Artiklar i publikationen
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Diabetes
- Av lärosätet
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Karolinska Institutet