Possible evidence of systemic lupus erythematosus and periodontal disease association mediated by Toll-like receptors 2 and 4

Abstract

Summary Toll‐like receptors (TLRs) participate in the innate immune response and trigger the immune responses of the body. Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown aetiology, characterized by an excessive autoimmune response in the body affecting the connective tissues. The disease is possibly triggered by both environmental aetiological factors and pathological organic processes such as exposure to sunlight, chronic infectious processes and genetic factors. Conversely, periodontal disease is an infectious disease caused by microorganisms in the oral cavity, resulting in a chronic inflammatory process which continuously stimulates the immune response, thus causing damage to the periodontal tissues. The expression of both TLR‐2 and TLR‐4 receptors are increased in both SLE and periodontal disease. Periodontitis might trigger excessive activation of immune response occurring in SLE by maintaining a high expression of TLRs, leading in turn to the acceleration of the onset and progression of autoimmune reactions. In addition, periodontal treatment is able to reduce the expression of these receptors and therefore the symptoms of SLE. Here we discuss the possible interaction between SLE and periodontitis, and suggest further studies evaluating common features in both factors that could explored, due to morbidity and mortality of SLE and the high incidence of periodontal infections around the world.

Association between oral lesions and disease activity in lupus erythematosus

“…[45][46][47] Although periodontal disease has local clinical manifestations, its chronic inflammatory nature can contribute to change, and even worsen, the course of rheumatoid arthritis and of other rheumatic diseases. 27,48,49 To our knowledge, our findings provide the strongest evidence to date for an association between gingivitis and higher disease activity of SLE. 27,48,49 To our knowledge, our findings provide the strongest evidence to date for an association between gingivitis and higher disease activity of SLE.…”

Cell Signaling Pathways That Regulate Antigen Presentation

“…Lastly, signaling via TLRs have been predominantly associated with infectious diseases (118-124); however, a variety of single-nucleotide polymorphisms in human TLRs have not only been associated with infectious and inflammatory (including autoimmune) diseases, but also with cancer (121, 123-126). As such, TLRs have been looked at as potential targets for immune-based therapy against infectious diseases (118, 119), as well as sepsis-associated pathology (118).…”

Periodontal Disease and Autoimmunity: What We Have Learned from Microbiome Studies in Rheumatology

“…Certain genetic variants which alter the inflammatory process and lead to impaired clearance of immunoglobulins have been implicated. Estrogen-driven stimulation of humeral activity may at least in part explain the female predominance [108]. Known environmental factors include UV light, demethylating drugs and infections such as EBV virus.…”

“…Activation of TLRs which respond to specific pathogenassociated molecular patterns (PAMPs) such as Lipopolysaccharide produced by bacteria, triggers cell signaling pathways and release of pro-inflammatory cytokines. The overexpression of TLR-4 leads to autoimmune lupus and is essential for the production of anti-DsDNA antibodies found in SLE [108]. Therefore, the influence of the microorganisms in periodontal disease may affect the expression of TLRs in SLE and stimulate the autoimmune process.…”