A deficiency in one of the immune system's enzymes affects the severity of autoimmune diseases such as MS, and explains why the course of these diseases can vary so much. New findings give an insight into how this enzyme deficiency can be diagnosed, and could lead to new medicines, reveals a thesis from the Sahlgrenska Academy.
Multiple sclerosis (MS) and Guillain-Barré syndrome (GBS) – the two autoimmune diseases covered by the thesis – can follow vastly different courses, with symptoms ranging from insignificant to life-threatening, the reason for which has been largely unknown. In the thesis the researchers have now found a factor in the immune defence that can explain this mechanism.
The immune system's white blood cells play an important role in the fight against invading micro-organisms. They contain an enzyme called NADPH oxidase, which converts oxygen into reactive oxygen radicals. It has long been known that these oxygen radicals stop infections by breaking down micro-organisms. New studies using animal models have shown that inadequate production of oxygen radicals can lead to the development of autoimmune diseases, where a patient's immune system attacks the body's own tissues. This would indicate that oxygen radicals are important for preventing the occurrence of autoimmune diseases.
"We wanted to look at this in humans, and examined the NADPH oxidase in the white blood cells of patients with MS, GBS and recurring GBS (RGBS)," says Natalia Mossberg, doctoral student at the Institute of Neuroscience and Physiology at the Sahlgrenska Academy. "The results show that patients with more severe forms of the illness have lower levels of oxygen radical production in their white blood cells as a result of deficient NADPH oxidase function."
The researchers discovered that the body's ability to produce reactive oxygen radicals at an early stage in the immune defence against infections has a major impact on how these illnesses develop. "We've shown that a strong but controlled production of oxygen radicals by the immune system is important for subduing illnesses such as MS and GBS," says Mossberg.
The researchers think that this method of measuring oxygen radical production in white blood cells can be used for investigating other autoimmune diseases and for diagnosing the severity of these illnesses. The discovery could also lead to a new approach to the treatment of MS in its early stages with medicines that trigger the production of NADPH oxidase or a vaccination for people at risk of developing this type of illness.
AUTOIMMUNE DISEASES
Multiple sclerosis is a chronic autoimmune disease of the central nervous system with periodic relapses that often develop into ever-increasing paralysis and balance problems. Treatment with medication is effective to some extent during the early stages of the illness. Guillain-Barré syndrome is the equivalent autoimmune disease of the peripheral nervous system that manifests itself in acute paralysis, though most patients who develop it return to full health. These illnesses result from inflammatory damage to the nerve cells' protective sheath, though hereditary factors also play a role.