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Titolo:
Isolation and functional characterization of recombinant GAD65 autoantibodies derived by IgG repertoire cloning from patients with type 1 diabetes
Autore:
Jury, K; Sohnlein, P; Vogel, M; Richter, W;
Indirizzi:
Univ Heidelberg, Dept Orthoped Surg, D-69118 Heidelberg, Germany Univ Heidelberg Heidelberg Germany D-69118 , D-69118 Heidelberg, Germany Univ Ulm, Dept Internal Med, Ulm, Germany Univ Ulm Ulm GermanyUniv Ulm, Dept Internal Med, Ulm, Germany Inselspital Bern, Inst Immunol & Allergol, CH-3010 Bern, Switzerland Inselspital Bern Bern Switzerland CH-3010 gol, CH-3010 Bern, Switzerland
Titolo Testata:
DIABETES
fascicolo: 9, volume: 50, anno: 2001,
pagine: 1976 - 1982
SICI:
0012-1797(200109)50:9<1976:IAFCOR>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN MONOCLONAL-ANTIBODIES; ISLET-CELL ANTIBODIES; GLUTAMATE-DECARBOXYLASE; AUTOREACTIVE EPITOPE; IMMUNE-RESPONSE; B-LYMPHOCYTES; IN-VIVO; INSULIN; ANTIGEN; LIBRARIES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Richter, W Univ Heidelberg, Dept Orthoped Surg, Schlierbacher Landstr 200,D-69118 Heidelberg, Germany Univ Heidelberg Schlierbacher Landstr 200 Heidelberg Germany D-69118
Citazione:
K. Jury et al., "Isolation and functional characterization of recombinant GAD65 autoantibodies derived by IgG repertoire cloning from patients with type 1 diabetes", DIABETES, 50(9), 2001, pp. 1976-1982

Abstract

The generation of human monoclonal autoantibodies is critical for understanding humoral immune responses in autoimmunity. In this study, we isolated the first human recombinant antibodies to glutamate decarboxylase (rGAD65ab) by IgG repertoire cloning, phage display of Fab fragments, and biopanningfrom two patients at onset of type 1 diabetes. We demonstrate that naturalIg heavy- and light-chain pairings of autoantibodies can be isolated by the recombinant approach and have a major selection advantage over other rGAD65ab. Among eight rGAD65ab, three (rGAD65ab A-C) displayed all functional and structural properties of known disease-related GAD65ab, including reactivity in the enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), islet cell antibody (ICA) test, and variable gene usage. Dominant epitope recognition was directed to the previously defined epitope EP-1 in the middle of GAD65, corroborating its immunodominance in the molecule. New features, such as assay-dependent GAD65 reactivity and new epitope recognition,were observed in two rGAD65ab (D and E). These antibodies were positive inthe GAD65 ELISA and ICA test but not in the GAD65 RIA, providing the firstexamples for ICA with incongruent results in solid-phase and fluid-phase assays. In conclusion, phage display-derived antibodies reflected well the natural autoantibody response in type I diabetes and may allow further characterization of assay-dependent features of GAD65ab and the recognition of epitopes in solid- but not fluid-phase assays.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/21 alle ore 04:14:24