Infections and Autoimmunity: A Panorama

Abstract

For more than 2,000 years, it was thought that malignant spirits caused diseases. By the end of nineteenth century, these beliefs were displaced by more modern concepts of disease, namely, the formulation of the "germ theory," which asserted that bacteria or other microorganisms caused disease. With the emergence of chronic degenerative and of autoimmune diseases in the last century, the causative role of microorganisms has been intensely debated; however, no clear explanatory models have been achieved. In this review, we examine the current available literature regarding the relationships between infections and 16 autoimmune diseases. We critically analyzed clinical, serological, and molecular associations, and reviewed experimental models of induction of and, alternatively, protection from autoimmune diseases by infection. After reviewing several studies and reports, a clinical and experimental pattern emerges: Chronic and multiple infections with viruses, such as Epstein-Barr virus and cytomegalovirus, and bacteria, such as H. pylori, may, in susceptible individuals, play a role in the evolvement of autoimmune diseases. As the vast majority of infections pertain to our resident microbiota and endogenous retroviruses and healthy carriage of infections is the rule, we propose to focus on understanding the mechanisms of this healthy carrier state and what changes its configurations to infectious syndromes, to the restoration of health, or to the sustaining of illness into a chronic state and/or autoimmune disease. It seems that in the development of this healthy carriage state, the infection or colonization in early stages of ontogenesis with key microorganisms, also called 'old friends' (lactobacilli, bifidobacteria among others), are important for the healthy living and for the protection from infectious and autoimmune syndromes.

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

“…Autoimmunity often develops subsequent to other injurious processes (e.g., infections, cancer) by "bystander mechanisms," epitope spread or mimicry, or other poorly understood mechanisms (6,(39)(40)(41)(42). In some cases, these "new" autoimmune responses can cause striking additional morbidity (e.g., carditis or nephritis following otherwise self-limited streptococcal infections, neurologic deficit syndromes associated with transient viral infections, neoplasms) (39,40).…”

“…In some cases, these "new" autoimmune responses can cause striking additional morbidity (e.g., carditis or nephritis following otherwise self-limited streptococcal infections, neurologic deficit syndromes associated with transient viral infections, neoplasms) (39,40). Thus, there are numerous biological precedents that could plausibly explain the development of autoimmunity in IPF as a secondary consequence of another, distinctly different lung injury(ies) that actually triggers the disease.…”

Fibrosis: ultimate and proximate causes

“…The overwhelming preponderance of these secondary autoimmune responses appear to be clinically benign, but they are highly pathogenic in an important minority of cases, including carditis, nephritis, neurologic dysfunction associated with group A streptococcal and other microbial infections, paraneoplastic syndromes linked to malignancies, and myriad other tissue-specific autoimmune disorders (15)(16)(17). The cascade of injury processes evoked by autoimmune responses can include direct cytotoxicities by autoantibodies or autoreactive T cells; elaboration of numerous proinflammatory, vasoactive, and profibrotic mediators (including IL-4, IL-13, and TGF-β); and recruitment and/or activation of other immune effectors and mesenchymal cells (18)(19)(20).…”

The Relationship of Systemic Lupus Erythematosus and Helicobacter Pylori

“…In the pathogenesis of SLE, several infectious agents have been held responsible such as cytomegalovirus, parvovirus B19 and Epstein Barr virus (EBV) [1,2]. There is a variable relationship between SLE and helicobacter, which is different from that of lupus and other infections.…”