Rheumatology: Current Research
Open Access

Novel self-organized criticality theory of autoimmunity explaining the cause of SLE

International Conference and Exhibition on Orthopedics & Rheumatology

August 13-15, 2012 Hilton Chicago/Northbrook, USA

Shunichi Shiozawa

Accepted Abstracts: Rheumatology & Orthopedics

Abstract :

Since the discovery of LE (lupus erythematosus) cell by Haargraves, reactivity against self has been considered the cause of autoimmune diseases. However, recent immunology tells that autoreactive clones are not forbidden and autoantibodies are seen ubiquitously in various diseases. Thus, Mackeyâ�?�?s autoimmune disease theory must be amended or re-considered. We have, instead, investigated the cause of SLE from a different angle, i.e., a view of systems biology, and found that systemic autoimmunity necessarily takes place when hostâ�?�?s immune system is over-stimulated by repeated exposure to antigen to levels that surpass systemâ�?�?s self-organized criticality. While Mackeyâ�?�?s theory requests autoreactivity as a pre-requisite, this novel â�?�?self-organized criticality theoryâ�?�? needs no pre-requisites. Methodology/Principal: Findings The method we have chosen was to overstimulate immune system maximally with antigen to the levels far beyond its steady-state, i.e., high-zone tolerance. The results show that systemic autoimmunity necessarily takes place when hostâ�?�?s immune system is overstimulated by repeated exposure to antigen to levels that surpass systemâ�?�?s self-organized criticality. We have repeatedly immunized mice normally not prone to autoimmune disease with the same antigen including OVA, KLH or SEB, and discovered that such repeated immunization by any antigen reproducibly led to the development of systemic autoimmunity, i.e., SLE. Further, autoantibodies are induced not by cross-reaction to antigen but by de novo T cell receptor (TCR) revision, i.e., V(D)J recombination, at periphery in spleen, which gives rise to a novel T cell type we term an autoantibodyinducing CD4 T cell (aiCD4 T cell). The aiCD4 T cell not only stimulated B cells to generate varieties of autoantibodies but also helped final differentiation of CD8 T cell into cytotoxic T lymphocyte (CTL) via antigen cross-presentation to induce lupus tissue injury, with 100% efficiency. While the TCR�?² chain of aiCD4 T cell was never revised, the TCR�?± chain was rearranged, which means that exogenous antigen drives CD4 T cell proliferation via by TCR�?² at periphery in spleen whereas auto-reactivity could be acquired via TCR�?± revision. Conclusions/Significance: As to whether or not repeated immunization with antigen makes sense in a real world, the answer would be yes, since our immune system is built up on a delicate balance between pathogen-induced tissue injury and defenseinduced tissue injury: host dies if pathogen is too strong due to the former and host also dies if immune defense is too strong due to the latter because the battle field is our body. To avoid both types of injury, we suppress, but not eradicate, pathogens to avoid exhaustive battle in the body, and thus, pathogens invade into body repeatedly below sea-level. Thus, the ability of a certain antigen to cause SLE depends on its propensity to be presented and/or cross-presented to overstimulate CD4 and/or CD8 T cells of the host beyond his/her critical limit, i.e., self-organized criticality.