Interferon regulatory factor 5 is a potential target of autoimmune response triggered by Epstein-barr virus and Mycobacterium avium subsp. paratuberculosis in rheumatoid arthritis: investigating a mechanism of molecular mimicry.

Authors:
Marco Bo
Marco Bo
University of Turin
Worcester | United States
Gian Luca Erre
Gian Luca Erre
University of Sassari
Italy
Magdalena Niegowska
Magdalena Niegowska
Università di Sassari
Italy
Marco Piras
Marco Piras
Orthopedic Department
Loredana Taras
Loredana Taras
AOU and University of Sassari
Italy
Maria Giovanna Longu
Maria Giovanna Longu
University Hospital of Sassari (AOUSS) Sassari
Italy
Giuseppe Passiu
Giuseppe Passiu
University La Sapienza
Italy
Leonardo A Sechi
Leonardo A Sechi
University of Udine
Udine | Italy

Clin Exp Rheumatol 2018 May-Jun;36(3):376-381. Epub 2018 Jan 15.

Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari, Italy.

Objectives: Rheumatoid arthritis (RA) is a chronic disease characterised by a pro-inflammatory cytokines linked erosive joint damage and by humoral and cellular response against a broad range of self-peptides. Molecular mimicry between Epstein-Barr virus (EBV), Mycobacterium avium subsp. paratuberculosis (MAP) and host peptides has long been regarded as an RA pathogenetic mechanism. Using bioinformatic analysis we identified high sequence homology among interferon regulatory factor 5 (IRF5), EBV antigen BOLF1 and MAP antigen MAP_4027. Our objective was to evaluate the presence in sera of RA patients of antibodies (Abs) directed against human homologous IRF5 cross-reacting with BOLF1 and MAP_4027.

Methods: Frequency of reactivity against IRF5424-434, BOLF1305-320 and MAP_402718-32 was tested by indirect ELISA in sera from 71 RA patients and 60 healthy controls (HCs).

Results: RA sera show a remarkable high frequency of reactivity against IRF5424-434 in comparison to HCs (69% vs. 8%; p<0.0001). Similarly, seroreactivity against BOLF1305-320 was more frequently detected in RA sera than in HCs counterpart (58% vs. 8%; p<0.0001). Frequency of Abs against MAP_402718-32 was 17% in RA sera vs. 5% in HCs with a p-value at the threshold level (p<0.051). Prevalence of Abs against at least one of the assessed epitopes reached 72% in RA patients and 15% among HCs. Levels of Abs in RA patients were significantly related to systemic inflammation.

Conclusions: IRF5 is a potential autoimmune target of RA. Our results support the hypothesis that EBV and MAP infections may be involved in the pathogenesis of RA, igniting a secondary immune response that cross-reacts against RA self-peptides.
July 2018
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