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Antibodies to post-translationally modified mitochondrial peptide PDC-E2(167–184) in type 1 diabetes
- Source :
- Archives of Biochemistry and Biophysics. 659:66-74
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Background Mitochondria play a role in type 1 diabetes (T1D) particularly in the treatment and prevention of disorder consequences. Due to their demonstrated role in diabetes pathology, mitochondrial proteins can be an interesting starting point to study candidate antigens in T1D. We investigated the role of relevant post-translational modifications (PTM) on a synthetic mitochondrial peptide as putative antigen. Methods The antibody response in T1D was evaluated by solid phase-ELISA using a collection of synthetic peptides bearing different PTMs. We investigated the role of lipoylation, phosphorylation, and glycosylation. The PTMs were introduced at position 173 of the mitochondrial pyruvate dehydrogenase E2 complex peptide PDC-E2(167–184) and at position 7 of a structure-based designed β-turn peptide as an irrelevant sequence to investigate the role of the specific PDC-E2 peptide sequence. Results IgM titres in 31 T1D patients were higher than IgGs to all the synthetic PTM peptides. Results demonstrated the crucial role of lysine lipoamide, serine O-phosphorylation, and O-glycosylation into the PDC-E2(167–184) peptide sequence for IgM antibody recognition. Conclusions Results highlight the importance of immune dysregulation in T1D, furthermore, if confirmed in a large number of patients, they will contribute to add novel diagnostic markers for the understanding the physiopathology of the disease.
- Subjects :
- Adult
Male
0301 basic medicine
Glycosylation
Biophysics
Antibody response
Lysine lipoamide
Mitochondrial peptide
Serine O-Glycosylation
Serine O-phosphorylation
Peptide
Mitochondrion
Biochemistry
Antibodies
Mitochondrial Proteins
Serine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Antigen
Humans
Phosphorylation
Molecular Biology
Peptide sequence
chemistry.chemical_classification
Thioctic Acid
biology
Stereoisomerism
Peptide Fragments
Diabetes Mellitus, Type 1
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
biology.protein
Female
Antibody
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 00039861
- Volume :
- 659
- Database :
- OpenAIRE
- Journal :
- Archives of Biochemistry and Biophysics
- Accession number :
- edsair.doi.dedup.....06db6ad351af63edd1f2417a12caf319