Emerging new pathways of pathogenesis and targets for treatment in systemic lupus erythematosus and Sjogren's syndrome.
OBJECTIVE
Systemic lupus erythematosus (SLE) and Sjogren's syndrome are chronic inflammatory diseases characterized by the dysfunction of T cells, B cells, and dendritic cells and the production of antinuclear autoantibodies. Here, we evaluate newly discovered molecular and cellular targets for the treatment of SLE and Sjogren's syndrome.


RESULTS
The mammalian target of rapamycin in T and B cells has been successfully targeted for treatment of SLE with rapamycin or sirolimus both in patients and animal models. Inhibition of oxidative stress, nitric oxide production, interferon alpha, toll-like receptors 7 and 9, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, and the nuclear factor kappa B pathway showed efficacy in animal models of lupus. B-cell depletion and blockade of anti-DNA antibodies and T-B cell interaction have shown success in animal models, whereas human studies have so far failed to accomplish clinical endpoints, possibly due to inadequacies in study design.


CONCLUSIONS
Discovery of novel genes and signaling pathways in lupus pathogenesis offers novel biomarker-targeted approaches for treatment of SLE and Sjogren's syndrome.
Perl
Andras
A
D000818:Animals; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy