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Glycated-H2A histone is better bound by serum anti-DNA autoantibodies in SLE patients: glycated-histones as likely trigger for SLE?
- Source :
-
Autoimmunity [Autoimmunity] 2015 Feb; Vol. 48 (1), pp. 19-28. Date of Electronic Publication: 2014 Jul 28. - Publication Year :
- 2015
-
Abstract
- Histones are the most abundant proteins associated with genomic DNA. Recent observations show that histones are quite susceptible to non-enzymatic glycation which results in the generation of free radicals causing structural perturbations. In this study, our aim is to define the role of deoxyribose-modified H2A histone in SLE initiation/progression. Glycation reaction was carried out by incubating H2A histone with 10 mM deoxyribose for 21 days at 37 °C. Structural changes in glycated-H2A were studied by various physico-chemical techniques. The antigen-antibody interaction was studied by direct binding, inhibition ELISA and mobility shift assay. Deoxyribose-modified-H2A histone showed increased hyperchromicity and increased fluorescence intensity. CD results demonstrated almost 50% loss in alpha helix conformation as a consequence of glycation. This was supported by an increase in Tm value vis-à-vis thermal stability. Glycated-H2A showed cross linking in SDS-PAGE. SLE sera positive for anti-nDNA autoantibodies showed preference for deoxyribose-modified-H2A histone compared to native H2A histone or native DNA. Inhibition ELISA supported the above findings. Band shift assay further reiterated the preferential recognition of glycated-H2A over native H2A by SLE IgG autoantibodies. Deoxyribose-modified-H2A histone exhibited damage as revealed by various physico-chemical studies. Glycation of H2A has resulted in the generation of neo-epitopes on H2A histone, which are preferably bound by SLE anti-nDNA autoantibodies. It implies that deoxyribose-modified-H2A may trigger immune response resulting in the generation of anti-glycated H2A antibodies with DNA cross reacting properties.
- Subjects :
- Adolescent
Adult
Animals
Antibodies, Antinuclear metabolism
Antigen-Antibody Complex metabolism
Binding, Competitive
Case-Control Studies
Cattle
DNA chemistry
Deoxyribose chemistry
Electrophoretic Mobility Shift Assay
Female
Glycosylation
Histones chemistry
Humans
Immunoglobulin G metabolism
Lupus Erythematosus, Systemic immunology
Lupus Erythematosus, Systemic pathology
Middle Aged
Protein Binding
Protein Stability
Protein Structure, Secondary
Antibodies, Antinuclear chemistry
Antigen-Antibody Complex chemistry
Histones immunology
Immunoglobulin G chemistry
Lupus Erythematosus, Systemic blood
Subjects
Details
- Language :
- English
- ISSN :
- 1607-842X
- Volume :
- 48
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 25065453
- Full Text :
- https://doi.org/10.3109/08916934.2014.941059