Diagnosing Neurological Autoimmune Disease

Autoimmune disease of the central nervous system results in a range of neurological and psychiatric symptoms. However, if diagnosed and treated early, immunotherapy is associated with a positive outlook. By retrospectively analysing the sera of patients suffering from a range of neurological and psychiatric symptoms, researchers from the University of Oxford, led by Professor Angela Vincent, have identified the presence of autoantibodies that target the ƴ2 subunits of the GABAA receptor. Through screening a large array of samples, antibodies were found in the sera of patients exhibiting a range of symptoms, whereas no antibodies were found in samples from healthy individuals. Furthermore, one patient suffering from treatment-resistant catatonia made a substantial improvement following immunotherapy, which correlated with autoantibody levels. This discovery will enable improved neurological and psychiatric diagnosis, allowing patients with this variant of autoimmune disorder to be identified early and treated appropriately.

Protection turned on oneself

Our immune system provides a critical defence against foreign and potentially harmful invaders. However, autoimmunity is a misguided response where renegade immune cells are unable to differentiate self from non-self, resulting in the destruction of the body’s own cells.

Autoimmune disorders affect 5-10% of the population and often involve antibodies against proteins of the central nervous system. This can result in a number of neurologic disorders, including encephalopathies, and subgroups of epilepsies and psychiatric disease.  However, once the specific antibodies have been identified, prompt diagnosis and therapy can occur.

 

Revealing a target of GABA autoimmunity

The GABAA receptor is the principle mediator of inhibitory synaptic transmission in the human brain and is the target for many therapeutic drugs, such as treatments for anxiety, insomnia and epilepsy.

By retrospectively analysing the sera of patients suffering from a range of neurological and psychiatric symptoms, researchers from the University of Oxford have identified the α1 and ƴ2 subunits of the GABAA receptor as a target of autoimmunity (published in the journal Neurology, Pettingill et al., 2015). Patients who expressed antibodies for α1 and ƴ2 subunits exhibited a range of disorders, including seizures, memory impairments, anxiety and psychosis. Furthermore, when the antibody-containing serum from these patients was washed over neuronal cultures, it resulted in a specific down-regulation of α1 and ƴ2 subunit expression, indicative of a causative effect.

It was also found that immunotherapy was beneficial in this group of α1/ƴ2 autoimmune patients, with one boy suffering from severe catatonia twice exhibiting substantial immunotherapy-mediated improvement that correlated with normalisation of his GABAA antibody levels.

 

A tool for diagnosis and therapy

Autoimmune channelopathies may have a good prognosis, especially if diagnosed and treated early. This discovery provides the rationale for improving diagnosis and prognosis for this newly identified GABAA α1 and ƴ2 variant of central nervous system autoimmune disease.

Oxford University Innovation has filed a United Kingdom provisional patent application GB1409234.0 (23rd May 2014) and would welcome discussions with companies engaged in autoimmunity research and those interested in incorporating this discovery into their antibody screening technology.

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