Rheumatoid arthritis patient antibodies highly recognize IL-2 in the immune response pathway involving IRF5 and EBV antigens

• Published in: Scientific reports Vol. 8; no. 1; pp. 1789 - 8
• Main Authors: Bo, Marco, Niegowska, Magdalena, Erre, Gian Luca, Piras, Marco, Longu, Maria Giovanna, Manchia, Pierangela, Manca, Mario, Passiu, Giuseppe, Sechi, Leonardo A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.01.2018; Nature Publishing Group
• Subjects: 14; 631/250/38; 692/4023; 82/1; 82/75; 82/79; Antibodies; Antibodies, Viral - immunology; Antigens; Antigens, Viral - immunology; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - virology; Autoimmune diseases; Autoimmune Diseases - immunology; Autoimmune Diseases - virology; Case-Control Studies; Cross Reactions - immunology; Cross-reaction; Environmental factors; Epitopes; Epitopes - immunology; Epstein-Barr virus; Epstein-Barr Virus Infections - immunology; Female; Genomes; Herpesvirus 4, Human - immunology; Humanities and Social Sciences; Humans; Immune response; Immunological tolerance; Interferon regulatory factor; Interferon Regulatory Factors - immunology; Interleukin 2; Interleukin-2 - immunology; Lymphocytes T; Male; Middle Aged; Mimicry; Molecular Mimicry - immunology; multidisciplinary; Rheumatoid arthritis; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-19957-z

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a progressive joint damage due to largely unknown environmental factors acting in concert with risk alleles conferring genetic susceptibility. A major role has been attributed to viral infections that include past contacts with Epstein-Barr virus (EBV) and, more recently, to non-protein coding sequences of human endogenous retrovirus K (HERV-K) integrated in the human genome. Molecular mimicry between viral and self proteins is supposed to cause the loss of immune tolerance in predisposed hosts. There are evidences that anti-IL-2 antibodies (Abs) are present in subjects affected by autoimmune diseases and may be responsible for alterations in regulatory T cell responses. In this study, we evaluated the levels of Abs against IL-2, viral epitopes and interferon regulatory factor 5 (IRF5) in 140 RA patients and 137 healthy controls (HCs). Ab reactivity reached the highest levels for IRF5, EBV and IL-2 (56%, 44% and 39%, respectively) in RA with significantly lower values among HCs (7–9%, p  < 0.0001), which suggests a possible cross-reaction between IRF5/EBV homologous antigens and shifts in T cell balance disrupted by anti-IL-2 Abs.