Munz C, Lunemann JD, Getts MT et al.Antiviral immune responses: triggers of or triggered by autoimmunity? Nat Rev Immunol 9:246-258

Viral Immunobiology, Institute of Experimental Immunology, University Hospital Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Nature Reviews Immunology (Impact Factor: 34.99). 05/2009; 9(4):246-58. DOI: 10.1038/nri2527
Source: PubMed


The predisposition of individuals to several common autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis, is genetically linked to certain human MHC class II molecules and other immune modulators. However, genetic predisposition is only one risk factor for the development of these diseases, and low concordance rates in monozygotic twins, as well as the geographical distribution of disease risk, suggest the involvement of environmental factors in the development of these diseases. Among these environmental factors, infections have been implicated in the onset and/or promotion of autoimmunity. In this Review, we outline the mechanisms by which viral infection can trigger autoimmune disease and describe the pathways by which infection and immune control of infectious disease might be dysregulated during autoimmunity.

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    • "Molecular mimicry defines the possibility that antigens from microorganisms can activate T-lymphocytes cross-reacting with self-antigens that share similar linear or conformational structures [66]. By now mimicry mechanisms involving viral proteins are recognized to play a key role in the pathogenesis of several human autoimmune diseases [66]. In the case of anti-CYP auto-reactivity, mimicry between HCV proteins E1, NS3, NS5a and NS5b and CYP2D6 accounts for the development of LKM-1 auto-antibodies [15] [18] [67] and T-cells antigens in CYP2D6, CYP2A6 and CYP2A7 [13] [68]. "
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    ABSTRACT: Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD) and chronic hepatitis C (CHC). In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression. Copyright © 2014. Published by Elsevier B.V.
    11/2014; 3C:72-78. DOI:10.1016/j.redox.2014.11.004
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    • "[126] The possible roles of polyreactive Abs in viral diseases, autoimmunity, and B cell malignancies are currently the subject of intense research but are still poorly understood. [86] [127] ANTIBODY HETEROSPECIFICITY "
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    ABSTRACT: The concept of antibody specificity is analyzed and shown to reside in the ability of an antibody to discriminate between two antigens. Initially, antibody specificity was attributed to sequence differences in complementarity determining regions (CDRs), but as increasing numbers of crystallographic antibody-antigen complexes were elucidated, specificity was analyzed in terms of six antigen-binding regions (ABRs) that only roughly correspond to CDRs. It was found that each ABR differs significantly in its amino acid composition and tends to bind different types of amino acids at the surface of proteins. In spite of these differences, the combined preference of the six ABRs does not allow epitopes to be distinguished from the rest of the protein surface. These findings explain the poor success of past and newly proposed methods for predicting protein epitopes. Antibody polyspecificity refers to the ability of one antibody to bind a large variety of epitopes in different antigens, and this property explains how the immune system develops an antibody repertoire that is able to recognize every antigen the system is likely to encounter. Antibody heterospecificity arises when an antibody reacts better with another antigen than with the one used to raise the antibody. As a result, an antibody may sometimes appear to have been elicited by an antigen with which it is unable to react. The implications of antibody polyspecificity and heterospecificity in vaccine development are pointed out. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Molecular Recognition 11/2014; 27(11). DOI:10.1002/jmr.2394 · 2.15 Impact Factor
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    • "It has been suggested that HSV-1 encoded UL6 (residues 299–314) induces autoreactive T-cells causing herpetic stromal keratitis [118]. It is a matter of debate, though, whether molecular mimicry is the key to disease development or if crossreactivity in combination with bystander functions and tissue damage is necessary to set off pathologic immune responses [119–121]. "
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    ABSTRACT: Human cytomegalovirus (HCMV) represents a prototypic pathogenic member of the β -subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE), systemic sclerosis (SSc), diabetes mellitus type 1, and rheumatoid arthritis (RA) is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28- T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.
    BioMed Research International 04/2014; 2014:472978. DOI:10.1155/2014/472978 · 2.71 Impact Factor
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