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Characteristics of in-vitro phenotypes of glutamic acid decarboxylase 65 autoantibodies in high-titre individuals
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- Chéramy, Mikael (författare)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Hampe, Christiane S. (författare)
- Department of Medicine, University of Washington, Seattle, WA, USA
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- Ludvigsson, Johnny (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Pediatrik,Hälsouniversitetet,Barn- och ungdomskliniken i Linköping
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- Casas, Rosaura (författare)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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(creator_code:org_t)
- 2013-02-04
- 2013
- Engelska.
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Ingår i: Clinical and Experimental Immunology. - : John Wiley & Sons. - 0009-9104 .- 1365-2249. ; 171:3, s. 247-254
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://www.ncbi.nlm...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Previous studies have indicated phenotypical differences in glutamic acid decarboxylase 65 autoantibodies (GADA) found in type 1 diabetes (T1D) patients, individuals at risk of developing T1D and stiff-person syndrome (SPS) patients. In a Phase II trial using aluminium-formulated GAD65 (GAD-alum) as an immunomodulator in T1D, several patients responded with high GADA titres after treatment, raising concerns as to whether GAD-alum could induce GADA with SPS-associated phenotypes. This study aimed to analyse GADA levels, immunoglobulin (Ig)G1–4 subclass frequencies, b78- and b96·11-defined epitope distribution and GAD65 enzyme activity in sera from four cohorts with very high GADA titres: T1D patients (n = 7), GAD-alum-treated T1D patients (n = 9), T1D high-risk individuals (n = 6) and SPS patients (n = 12). SPS patients showed significantly higher GADA levels and inhibited the in-vitro GAD65 enzyme activity more strongly compared to the other groups. A higher binding frequency to the b78-defined epitope was found in the SPS group compared to T1D and GAD-alum individuals, whereas no differences were detected for the b96·11-defined epitope. GADA IgG1–4 subclass levels did not differ between the groups, but SPS patients had higher IgG2 and lower IgG4 distribution more frequently. In conclusion, the in-vitro GADA phenotypes from SPS patients differed from the T1D- and high-risk groups, and GAD-alum treatment did not induce SPS-associated phenotypes. However, occasional overlap between the groups exists, and caution is indicated when drawing conclusions to health or disease status.
Nyckelord
- GAD65 immunotheraphy; GADA; stiff-person syndrome; type 1 diabetes
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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