Lack of Evidence of Rotavirus-dependent Molecular Mimicry As a Trigger of Coeliac Disease
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New data suggest the involvement of rotavirus (RV) in triggering autoimmunity in coeliac disease (CD) by molecular mimicry between the human-transglutaminase protein and the dodecapeptide (260-271 aa) of the RV protein VP7 (pVP7). To assess the role of RV in the onset of CD, we measured anti-pVP7 antibodies in the sera of children with CD and of control groups. We analysed serum samples of 118 biopsy-proven CD patients and 46 patients with potential CD; 32 children with other gastrointestinal diseases; 107 no-CD children and 107 blood donors. Using enzyme-linked immunosorbent assay (ELISA) assay, we measured immunoglobulin (Ig)A-IgG antibodies against the synthetic peptides pVP7, the human transglutaminase-derived peptide (476-487 aa) which shows a homology with VP7 protein and a control peptide. The triple-layered RV particles (TLPs) containing the VP7 protein and the double-layered RV-particles (DLPs) lacking the VP7 protein were also used as antigens in ELISA assay. Antibody reactivity to the RV-TLPs was positive in 22 of 118 (18%) CD patients and in both paediatric (17 of 107, 16%) and adult (29 of 107, 27%) control groups, without showing a statistically significant difference among them (P = 0·6, P = 0·1). Biopsy-proven CD patients as well as the adult control group demonstrated a high positive antibody reactivity against both pVP7 (34 of 118, 29% CD patients; 66 of 107, 62% adult controls) and control synthetic peptides (35 of 118, 30% CD patients; 56 of 107, 52% adult controls), suggesting a non-specific response against RV pVP7. We show that children with CD do not have higher immune reactivity to RV, thus questioning the molecular mimicry mechanism as a triggering factor of CD.
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Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease.
Ha E, Kim J, Cha H, Lee G, Shin J, Shin Y JAMA Netw Open. 2023; 6(7):e2324532.
PMID: 37494043 PMC: 10372702. DOI: 10.1001/jamanetworkopen.2023.24532.
Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy.
Paolella G, Sposito S, Romanelli A, Caputo I Int J Mol Sci. 2022; 23(14).
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Benitez-Paez A, Olivares M, Szajewska H, Piescik-Lech M, Polanco I, Castillejo G Front Microbiol. 2020; 11:1335.
PMID: 32655529 PMC: 7324710. DOI: 10.3389/fmicb.2020.01335.
Akobeng A, Singh P, Kumar M, Al Khodor S Eur J Nutr. 2020; 59(8):3369-3390.
PMID: 32651763 PMC: 7669811. DOI: 10.1007/s00394-020-02324-y.