Glycoxidation of mammalian whole histone generates highly immunogenic aggregates: Sera of SLE patients contain autoantibodies against aggregates.
Scand J Immunol
; 100(3): e13389, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38816907
ABSTRACT
Non-enzymatic glycation and oxidation of self-proteins, causing formation and accumulation of advanced glycation end products (AGEs), have been reported in an array of pathologies, including systemic lupus erythematosus (SLE). Such modifications may generate neo-epitopes, break immunological tolerance, and induce antibody response. In this study, we have first analysed the structural modifications of whole histone in the presence of deoxyribose followed by oxidation with hydroxyl radicals. Changes in the secondary and tertiary structure of the whole histone were determined by spectroscopic techniques and biochemical assays. Fluorescence spectroscopy and UPLC-MS showed the generation of AGEs such as carboxymethyl lysine and pentosidine, while DLS and TEM indicated the presence of amorphous AGE-aggregates. Moreover, rabbits immunized with these histone-AGEs exhibited enhanced immunogenicity and ELISA and western immunoblot of IgG antibodies from SLE patients' sera showed a significantly higher specificity towards modified histone-AGEs than the native histone.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxirredução
/
Autoanticorpos
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Histonas
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Produtos Finais de Glicação Avançada
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Lúpus Eritematoso Sistêmico
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Scand J Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia