Autoimmune Disease pH and Temperature.

Perhaps parts of the immune system are pH and temperature sensitive. If true, there could be a variance in pH and/or temperature under certain conditions that could impact the immune system and vice versa. Possibly the illusive etiology of autoimmune disease is in part due to pH and/or temperature changes. A majority would probably agree the human immune system is designed to destroy foreign invasion such as an infection and/or for removal of nonviable tissue such as that damaged by trauma. Obviously, both of the previous situations would be more likely to involve at least a local environment trending more acidic. Also most would agree autoimmune disease is when there is an error in the immune system and the system begins to attack and destroy viable tissue. Thus could the etiology of autoimmune disease be a repair system gone awry possibly because of a pH and/ or temperature change? If cancer is the repair system gone awry in regard to overproduction of replacement cells, then perhaps autoimmune disease is the repair system gone awry in regard to the damaged cell removal causing disease possibly because of a pH and/or temperature change. When there is cell damage inflammation develops as certain cells infiltrate the area and certain mediators accumulate that are also part of the immune system. Autoantibodies have been noted to be present following trauma with some suspecting this is a mechanism to remove cellular debris. However, autoantibody presence suggests a possible autoimmune disease in the future but is not diagnostic, since many normal individuals have mild levels. For example, with diabetes mellitus type I, there can be an autoantibody present for years (or even a life time) without any overt disease ever developing. In short, autoimmunity may follow tissue damage with low levels of antibodies but not necessarily actual autoimmune disease with destruction of viable tissue. So this is similar to other situations where something could occur, but does not have to occur, or rather something is more likely to occur, but is still not a certainty. An unknown second step probably has to occur, could that second step involve a pH and/or temperature change is the question. If an individual develops an autoimmune disease, they are more likely to develop a second autoimmune disease than are other patients. Autoimmune diseases seem to run in families as well. There appears to be a genetic susceptibility. Some say autoimmune diseases are multigenic, heterogeneous in genetic basis, with identical twins mixed on penetrance but usually higher than siblings and much higher than unrelated populations. If there is a pH aspect to the immune system, perhaps this involves the cellular pumps, channels, transporters and isoenzyme levels. This could account for a familial predisposition yet be multigenic, since there are so many different cellular pumps, channels, transporters and isoenzymes. There are multiples of each of these, so a particular combination could make an individual susceptible and this would be genetic. The cellular pumps, channels, transporters and isoenzymes could also respond to environmental stress changing to some degree accounting for differences in identical twins. The medications procainamide and hydralazine have been known for decades to induce autoimmune disease, specifically lupus. Procainamide impacts sodium channels while hydralazine impacts the calcium activated potassium channels and so both could impact pH levels. Interestingly, some compliment activation [1] and IgG binding [2] are more reactive in an acidic environment. In addition, some interleukins seem to prefer an acidic environment [3]. But there is also a possibility extreme levels of alkalinity can set the immune system into action as well, at the very least through cell destruction. Strong ions such as iodine in the thyroid could conceivably impact the cellular pumps, channels, transporters and isoenzymes. Indeed that is possibly what we see. As the level of intrathyroidal iodine increases, so does the incident of Hashimoto’s thyroiditis [4], one of the most common autoimmune diseases. However, not everyone develops Hashimoto’s thyroiditis with higher iodine, just some people. Could those with a certain mix of cellular pumps, channels, transporters and isoenzymes be the ones that are more likely to develop the Hashimoto’s thyroiditis? Also some cytokines such as interferon can induce Hashimoto’s thyroiditis. Could interferon possibly be impacting the cellular pumps, channels, transporters and isoenzymes? Yes, it is known to impact the potassium channels for example [5]. Finally, if pH changes enough there could be a charge generated which could impact movement possibly even for T and B cells. Another interesting aspect about autoimmune diseases is they are in general significantly more common usually in females than males. Women have increased antibody production compared to Manuscript accepted for publication April 10, 2014