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Autoimmune diseases are caused when the body makes antibodies that attack our own proteins.

Autoantibodies produced by the immune system can erroneously target host cells, leading to autoimmune diseases. Autoantibodies targeting the nervous system can cause conditions including as neuromyelitis optica and encephalitis. Although rare, these conditions can lead to permanent disability. Patients with these conditions can respond well to immunotherapies, but only after accurate diagnosis.

Between 2008 - 2015, researchers from the Oxford Autoimmune Neurology Group identified new autoantibody targets (LGI1, CASPR2, and the glycine receptor) which showed clinical utility in diagnosing patients with immunotherapy-responsive CNS diseases in which patients develop memory loss, seizures and psychiatric illness. As an example of this work, in 2010 the team discovered that autoantibodies in patients with neuromyotonia, Morvan’s syndrome or encephalitis, previously thought to bind the voltage gated potassium channel (VGKC), often bind two other proteins: LGI1 or CASPR2. Research showed that the autoantibodies against LGI1 and CASPR2 are associated with distinctive, well-defined syndromes, with diagnostic and prognostic value, and these patients almost universally responded to immunotherapies. Hence, these are widely considered “not-to-miss" neurological and psychiatric conditions. In contrast, patients with autoantibodies against the VGKC complex itself showed no distinct phenotypes and showed no clear response to immunotherapies

The team has also made significant advances in the development of accurate diagnostics.  Conventional laboratory tests use denatured or chemically modified autoantibody targets, or present intracellular components of autoantibody targets that are inaccessible to circulating autoantibodies in vivo, that may lead to poor test accuracy. To detect exclusively binding to the native extracellular domains of proteins, the researchers developed live-cell-based systems that present native surface targets to patient antibodies, to mimic what the circulating patient antibodies ‘see’ in vivo.

The Autoimmune Neurology Group now performs about 20,000 tests annually for UK patient care. Many of these have been evaluated in large multinational studies, leading to changes in laboratory practices across multiple international testing centres. This greater diagnostic accuracy has improved the worldwide clinical identification of patients who will respond to immunotherapies and prevented others from receiving inappropriate, potentially harmful, immunotherapies.