Abstract
Extensive work on experimental animal models clearly demonstrates that infectious agents can break immunological tolerance to self-antigens and induce autoimmune disorders, mainly systemic lupus erythematosus (SLE). The establishment of a causative link between infections and autoimmunity has been largely studied in a host of clinical studies, proving the role of infectious agents in the induction, as well as in the progression or exacerbation of SLE. However, we are far from a plain understanding of microbial-host interactions in the pathogenesis of SLE. Much serological, molecular and geoepidemiological evidence supports the relationship of different environmental infectious triggers in the inception of SLE-related autoimmune phenomena with adjuvant effects. The promotion of autoimmune responses through bystander activation or epitope spreading via multiple inflammatory pathways has been confirmed in animal models. Different viruses have been implicated in SLE pathogenesis, particularly Epstein-Barr virus, but also parvovirus B19, cytomegalovirus and retroviruses. SLE patients usually have an impaired immune response towards Epstein-Barr virus and dysregulation of the viral latency period. Furthermore, the accumulation of endogenous retroviral products might trigger the production of interferon and anti-DNA antibodies. In addition, protozoan infections might even protect from autoimmune processes and rescind an ongoing B cell activation. Herein, we discuss which type of infections induce, exacerbate or inhibit autoimmune disorders and analyze the principal infection-induced immunological mechanisms influencing the development of SLE.
Highlights
Autoimmunity is the result of self-tolerance breakdown and derives from an attack at the basis of the immune system on different organs and tissues, which are conceived of as foreign
Ram et al aimed to determine the presence of hepatitis B core antibody, a seromarker for past or present infection with hepatitis B virus (HBV), in a large number of sera collected from patients with different autoimmune disorders, but found an unexpected low percentage of specific antibodies in patients with systemic lupus erythematosus (SLE) in comparison to healthy blood donors: this finding elicited the hypothesis of HBV’s protective role for autoimmunity [60]
Much attention has been given to genetic research on the path to uncovering the underlying factors of autoimmunity, and many genome-wide association studies have identified numerous gene-disease associations for SLE, though the maintenance of autoaggressive responses and the development of clinically-overt disease have not been yet delineated
Summary
Autoimmunity is the result of self-tolerance breakdown and derives from an attack at the basis of the immune system on different organs and tissues, which are conceived of as foreign. Pediatric SLE, starting at an age less than 16 years, is usually more aggressive than SLE in adults and often involves major organs, including kidneys and central nervous system. The exact interaction of these infectious triggers and their interplay with genes that confer susceptibility to autoimmunity is still poorly defined. It is unknown why some, but not all individuals go on to develop full-blown SLE symptoms with disease flares, and the reasons underlying relapses and remissions in SLE are unraveled
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