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Investigation of immune complexes formed by mitochondrial antigens containing a new lipoylated site in sera of primary biliary cholangitis patients
- Source :
- Clin Exp Immunol
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
Abstract
- Summary Primary biliary cholangitis (PBC) is characterized by the presence of serum anti-mitochondrial autoantibodies (AMAs). To date, four antigens among the 2-oxo-acid dehydrogenase complex family, which commonly have lipoyl domains as an epitope, have been identified as AMA-corresponding antigens (AMA-antigens). It has recently been reported that AMAs react more strongly with certain chemically modified mimics than with the native lipoyl domains in AMA-antigens. Moreover, high concentrations of circulating immune complexes (ICs) in PBC patients have been reported. However, the existence of ICs formed by AMAs and their antigens has not been reported to date. We hypothesized that AMAs and their antigens formed ICs in PBC sera, and analyzed sera of PBC and four autoimmune diseases (Sjögren's syndrome, systemic lupus erythematosus, systemic scleroderma, and rheumatoid arthritis) using immune complexome analysis, in which ICs are separated from serum and are identified by nano-liquid chromatography-tandem mass spectrometry. To correctly assign MS/MS spectra to peptide sequences, we used a protein-search algorithm that including lipoylation and certain xenobiotic modifications. We found three AMA-antigens, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the E2 subunit of the 2-oxo-glutarate dehydrogenase complex (OGDC-E2) and dihydrolipoamide dehydrogenase binding protein (E3BP), by detecting peptides containing lipoylation and xenobiotic modifications from PBC sera. Although the lipoylated sites of these peptides were different from the well-known sites, abnormal lipoylation and xenobiotic modification may lead to production of AMAs and the formation ICs. Further investigation of the lipoylated sites, xenobiotic modifications, and IC formation will lead to deepen our understanding of PBC pathogenesis.
- Subjects :
- Adult
0301 basic medicine
Lipoylation
Immunology
Pyruvate Dehydrogenase Complex
Antigen-Antibody Complex
Autoantigens
Epitope
Pathogenesis
Epitopes
Young Adult
03 medical and health sciences
0302 clinical medicine
Immune system
Antigen
Tandem Mass Spectrometry
parasitic diseases
Humans
Immunology and Allergy
Aged
Autoantibodies
Aged, 80 and over
Dihydrolipoamide dehydrogenase
Liver Cirrhosis, Biliary
Chemistry
Autoantibody
Original Articles
Middle Aged
Pyruvate dehydrogenase complex
Molecular biology
Mitochondria
030104 developmental biology
Female
030215 immunology
Subjects
Details
- ISSN :
- 13652249 and 00099104
- Volume :
- 204
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Immunology
- Accession number :
- edsair.doi.dedup.....aebfae6af8f8de8d8b38900e58ec3394