Abstract
BackgroundA link between measles virus and Crohn’s disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry.MethodsThe BLAST2p program was used to identify amino acid sequence similarities between five measles virus and 56 intestinal proteins. Antibody responses to measles/human mimics were tested by an in-house ELISA using serum samples from 50 patients with CD, 50 with ulcerative colitis (UC), and 38 matched healthy controls (HCs).ResultsWe identified 15 sets of significant (>70%) local amino acid homologies from two measles antigens, hemagglutinin-neuraminidase and fusion-glycoprotein, and ten human intestinal proteins. Reactivity to at least one measles 15-meric mimicking peptide was present in 27 out of 50 (54%) of patients with CD, 24 out of 50 (48%) with UC (CD versus UC, p = 0.68), and 13 out of 38 (34.2%) HCs (CD versus HC, p = 0.08). Double reactivity to at least one measles/human pair was present in four out of 50 (8%) patients with CD, three out of 50 (6%) with UC (p = 0.99), and in three out of 38 (7.9%) HCs (p >0.05 for all). Titration experiments yielded different extinction curves for anti-measles and anti-human intestinal double-reactive antibodies. Epitope prediction algorithms and three-dimensional modeling provided bioinformatic confirmation for the observed antigenicity of the main measles virus epitopic regions.ConclusionsMeasles sequences mimicking intestinal proteins are frequent targets of antibody responses in patients with CD, but this reactivity lacks disease specificity and does not initiate cross-reactive responses to intestinal mimics. We conclude that there is no involvement of measles/human molecular mimicry in the etiopathogenesis of CD.
Highlights
A link between measles virus and Crohn’s disease (CD) has been postulated
Amino acid alignment A step-by-step approach of the design of the study related to the amino acid alignments leading to the construction of the mimicking pairs is provided as an additional file (Additional file 1)
This is the first study to report a lack of evidence in support of a mechanism of molecular mimicry and immunological cross-reactivity involving measles virus and human intestinal antigens, potentially targeted by CD-specific immune responses
Summary
A link between measles virus and Crohn’s disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry. Whilst data reported in the literature have suggested that there is persistent measles infection in patients with CD [13], other laboratories were unable to note serological [14] or molecular evidence of the virus in tissues of affected individuals [15]. These inconsistencies have left unanswered the question as to whether there is a connection between measles infection (and measles vaccination) and the development of CD [16,17]. Vaccinated individuals, as well as those individuals infected by measles virus, develop antibodies against measles virus glycoprotein (VGLF), an immunodominant viral antigen [23,24]
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