Reference | ||
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Reference Type | Literature | IEDB_Reference:1003368 |
Title | Does cross-reactivity between mycobacterium avium paratuberculosis and human intestinal antigens characterize Crohn's disease? | |
Authors | Dimitrios Polymeros; Dimitrios P Bogdanos; Richard Day; Dimitryi Arioli; Diego Vergani; Alastair Forbes | |
Affiliations | University College London, London, United Kindgom. | |
Journal | Gastroenterology | |
Year | 2006 | |
Abstract | BACKGROUND & AIMS: Most Crohn's disease (CD) patients show seroreactivity against Mycobacterium avium paratuberculosis (MAP), suggesting a pathogenic role for this organism. Our aim was to seek amino acid similarities between MAP and intestinal proteins that, through molecular mimicry, could serve as targets for cross-reactive immunity in CD. METHODS: Fifty-three peptides comprising 23 sets of MAP/human intestinal peptidyl mimics chosen for maximal homology were constructed and tested for immunologic cross-reactivity by enzyme-linked immunosorbent assay in 50 patients with CD, 50 with ulcerative colitis, and 38 healthy controls. RESULTS: Antibody reactivity was present in only 7 of 23 peptide sets. MAP/self-reactivity in at least 1 of the 7 reactive sets was present in 21 (42%) CD patients but was virtually absent in the controls. Significant double-reactivity was found against MAP glycosyl transferase d (gsd)(230-244)/human gastrointestinal glutathione peroxidase (GPg)(111-125) homologues in 15 of 50 (30%) CD patients; MAP alkylohydroperoxidase C (ahpC)(20-34)/human tumor overexpressed protein (TOG)(637-651) double-reactivity was present in 10 (20%) CD patients, but in none of the controls. Inhibition studies confirmed that simultaneous reactivity to mimics was caused by cross-reactivity. Three-dimensional modeling predicts GPg(111-125) will be exposed in a solvent-accessible surface region of the protein compatible with antibody recognition. Antibody affinity was greater for the MAP mimics than for the self-sequences, suggesting that reactivity to the mycobacterial sequences precedes that against self-sequences. CONCLUSIONS: We describe MAP/self-mimics as targets of cross-reactive antibody responses characterizing patients with CD. Our findings indicate gastrointestinal glutathione peroxidase as a novel autoantigen in CD. | |
Curation Last Updated | 2023-08-18 20:18:41 |
Epitope | ||
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Epitope ID | 133921 | IEDB_epitope:133921 |
Chemical Type | Linear peptide | |
Linear Sequence | QLELTEGMRFDKGYI | |
Source Molecule Name | heat shock protein 65 | |
Source Organism | Mycobacterium avium subsp. paratuberculosis (Mycobacterium avium paratuberculosis) | |
Starting Position | 184 | |
Ending Position | 198 |
Epitope Reference Details | ||
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Epitope Structure Defines | Epitope containing region/antigenic site | |
Epitope Name | MAP hsp65 184-198 | |
Location of Data in Reference | Table 1 |
Immunization | ||
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Host Organism | Homo sapiens (human) |
Host Details | ||
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Age | 19 to 83 years |
1st In Vivo Process | ||
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In Vivo Process Type | Occurrence of disease | OGMS:0000063 |
Disease State | Crohn's disease | |
Disease Stage | Chronic; | OGMS:0000064 |
Immunization Comments | ||
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Immunization Comments | Serum samples were taken from patients with Crohn's disease. All patients had well characterized CD based on clinical, endoscopic, radiologic, and histologic criteria. |
B Cell Assay | ||
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Qualitative Measurement | Positive | |
Method/Technique | ELISA | |
Measurement of | qualitative binding |
Measurement Details | ||
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Number of Subjects Tested | 50 | |
Number of Subjects Responded | 3 | |
Response Frequency (%) | 6 |
Assayed Antibody | ||
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Assayed Antibody Source Material | Serum | |
Assayed Antibody Immunoglobulin Domain | Entire Antibody | |
Assayed Antibody Purification Status | Polyclonal | |
Assayed Antibody Heavy Chain Type | IgG |
Antigen | ||
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Epitope Relation | Epitope | |
Chemical Type | Linear peptide | |
Linear Sequence | QLELTEGMRFDKGYI | |
Source Molecule Name | heat shock protein 65 | |
Source Organism | Mycobacterium avium subsp. paratuberculosis (Mycobacterium avium paratuberculosis) | |
Starting Position | 184 | |
Ending Position | 198 |
Assay Reference Details | ||
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Location of Assay Data in Reference | Table 2 |