Myasthenia gravis, like other autoimmune diseases, is a complex disease and a combination of different factors appear to contribute to its development, including environmental factors, smoking history, sex hormones, and exposure to certain viruses. Studies of identical twins have shown that some people have genetic risk factors that predispose them to acquiring the disease. Individuals with certain versions (alleles) of HLA genes are more likely to develop the disease. HLA genes encode proteins that present ‘antigens’ or foreign objects on the surface of cells, which are recognized by cells of the immune system (T cells) (Beisswanger 2007). Scientists discovered associations between the presence of certain HLA alleles and early-onset myasthenia gravis, late-onset myasthenia gravis, and thymic abnormalities. Other gene alleles have also been shown to be associated with myasthenia gravis, including PTPN22, CHRNA1, and CTLA-4 (Zagoriti 2013). It is hoped that by identifying possible genetic risk factors for myasthenia gravis, more effective treatment options or preventive therapies can be discovered.
Pesticides and Intermediate Myasthenia Syndrome
Exposure to some pesticides can induce symptoms resembling myasthenia gravis. Many pesticides contain chemicals called organophosphates that function by inhibiting acetylcholinesterase activity, resulting in an increase in acetylcholine levels. If an individual is exposed to high levels of organophosphate pesticides, the increased levels of acetylcholine can overwhelm the acetylcholine receptors, causing them to become dysfunctional (a phenomenon known as depolarization block); this can result in muscle weakness, heart rhythm abnormalities, and cholinergic crisis (increased bronchial secretions and subsequent breathing and swallowing problems), similar to what occurs following an overdose of acetylcholinesterase inhibitor medication. It is important to note that these symptoms are not related to an autoimmune response to the acetylcholine receptor (Dongren 1999; Yang 2005; He 1998; Yang 2007). It has been estimated that approximately 3 million people are poisoned by organophosphates each year (Jeyaratnam 1990; Kos 2013). Pesticide poisoning can manifest itself in three phases (Yang 2007):