Burton Abrams, a,
a221 Linden Drive, Elkins Park, PA 19027, United States
Received 6 August 2008; accepted 9 August 2008. Available online 25 September 2008.
Article Outline
References
Gout has been reported to have an unusually low coincidence with rheumatoid arthritis (RA) [1], systemic lupus erythematosus [2], and Parkinson’s disease [3]. RA and lupus have been established as autoimmune. Parkinson’s was hypothesized recently to be autoimmune [4]. This correspondence hypothesizes the physiological mechanism by which gout inhibits the development of these and other cell-mediated autoimmune diseases.
Gout and cell-mediated autoimmune disease have both been reported as consequences of sleep apnea, a gout flare within a few hours [5] and cell-mediated autoimmune disease over the long term [6]. The prevalence of sleep apnea in at least the mild form has been estimated to be 20% of the adult population in western countries [7], a much higher prevalence than gout or any autoimmune disease.
As described in [5] and [6], both conditions can result from the effects on the immune system of monosodium urate crystals (MSU), which precipitate as a result of the catabolic hyperuricemia and pulmonary acidosis caused by the frequent hypoxic intervals of sleep apnea. Once formed, even with a desirable serum uric acid concentration <6 mg/dl, MSU crystals have an half-life of many months before they are finally dissolved [8].
Most people with sleep apnea are not predisposed to gout, even though many of them precipitate MSU into nonsynovial connective tissue. In those not predisposed to gout, the MSU continues to up-regulate the immune system for many months by the maturation of dendritic cells and T cells [9], thereby increasing the likelihood of autoimmune development. Those who are predisposed to gout shield the MSU crystals from long-term sensing by MSU-activated dendritic cells, either by encasing the MSU crystals in tophi or by coating them while in synovium with a protein, primarily apo E which originates in synovium [10]. As a result of this protein coating, the duration of a single gout flare is typically only 3 to 10 days. It is also the hypothesized mechanism by which gout inhibits the development of those cell-mediated autoimmune diseases that result from the hypoxia of sleep apnea.
A consequence of this hypothesis may be that other diseases whose coincidence with gout are found to be unusually low but have not been recognized as autoimmune, should be suspected as being autoimmune. This recognition can lead to new understanding and new treatments for these diseases. Most importantly, individuals evidencing these diseases should be screened for sleep apnea and then treated appropriately.
References
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