Reference
Reference TypeLiterature
TitleDoes cross-reactivity between mycobacterium avium paratuberculosis and human intestinal antigens characterize Crohn's disease?
AuthorsDimitrios Polymeros; Dimitrios P Bogdanos; Richard Day; Dimitryi Arioli; Diego Vergani; Alastair Forbes
AffiliationsUniversity College London, London, United Kindgom.
JournalGastroenterology
Year2006
AbstractBACKGROUND & 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 Updated2023-08-18 20:18:41
Epitope
Epitope ID133921
Chemical TypeLinear peptide
Linear SequenceQLELTEGMRFDKGYI
Source Molecule Nameheat shock protein 65
Source OrganismMycobacterium avium subsp. paratuberculosis (Mycobacterium avium paratuberculosis)
Starting Position184
Ending Position198
Epitope Reference Details
Epitope Structure DefinesEpitope containing region/antigenic site
Epitope NameMAP hsp65 184-198
Location of Data in ReferenceTable 1
Immunization
Host OrganismHomo sapiens (human)
Host Details
Age19 to 83 years
1st In Vivo Process
In Vivo Process TypeOccurrence of diseaseOGMS:0000063
Disease StateCrohn's disease
Disease StageChronic;OGMS:0000064
Immunization Comments
Immunization CommentsSerum 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
Qualitative MeasurementPositive
Method/TechniqueELISA
Measurement ofqualitative binding
Measurement Details
Number of Subjects Tested50
Number of Subjects Responded3
Response Frequency (%)6
Assayed Antibody
Assayed Antibody Source MaterialSerum
Assayed Antibody Immunoglobulin DomainEntire Antibody
Assayed Antibody Purification StatusPolyclonal
Assayed Antibody Heavy Chain TypeIgG
Antigen
Epitope RelationEpitope
Chemical TypeLinear peptide
Linear SequenceQLELTEGMRFDKGYI
Source Molecule Nameheat shock protein 65
Source OrganismMycobacterium avium subsp. paratuberculosis (Mycobacterium avium paratuberculosis)
Starting Position184
Ending Position198
Assay Reference Details
Location of Assay Data in ReferenceTable 2