Antibody Linked to Higher Relapse Risk in Rare Neurological Disease 'MOGAD' Identified

Seoul National University Hospital research team analyzes 161 patients in South Korea and the UK
Analyzes antibodies to seven forms of the MOG protein
"Relapse risk significantly higher in MOG-alpha3 antibody-positive group"

A new antibody has been identified that may help assess the risk of relapse in MOG antibody-associated disease, a rare neurological disorder that can cause optic neuritis and myelitis. The antibody reacts to MOG-alpha3, a form of the MOG protein. Patients who tested positive were found to have about 2.7 times the relapse risk of those who tested negative.

Seoul National University Hospital said on November 11 that a joint research team had confirmed the findings after analyzing 161 patients in South Korea and the United Kingdom. The team included Professor Kim Seongmin of the Department of Neurology at Seoul National University Hospital, Dr. Patrick Waters of the University of Oxford in the UK, Professor Kwon Youngnam of the Department of Neurology at Kangbuk Samsung Hospital, and researchers from Oxford University Hospitals, including Miguel Rial Lato.

From left: Kim Seongmin, professor of neurology at Seoul National University Hospital, and Kwon Yeongnam, professor of neurology at Kangbuk Samsung Hospital. Seoul National University Hospital

MOG antibody-associated disease is an inflammatory disease of the central nervous system that occurs when the immune system attacks MOG proteins in the myelin sheath, which surrounds and protects nerve fibers. It can manifest as optic neuritis, myelitis, or encephalitis, and may cause vision loss, paralysis, and sensory disturbances.

Existing tests for MOG antibodies have mainly targeted MOG-alpha1, one form of the MOG protein. The protein exists in seven forms, or isoforms, depending on its structure inside cells, but the relationship between antibodies to other forms and the risk of relapse had not been clearly established.

The research team measured antibodies to all seven forms in serum samples from 56 Seoul National University Hospital patients and identified MOG-alpha3 as a candidate associated with relapse. The team then tested the association in 49 patients from eight hospitals in South Korea and 56 patients in Oxford, UK.

Among the Seoul National University Hospital patients, the proportion who relapsed during the entire follow-up period was 87.5% (7 of 8) in the MOG-alpha3 antibody-positive group and 43.8% in the negative group. The difference over the full period was not statistically significant, but the relapse rate within one year of disease onset was significantly higher in the positive group, at 87.5%, than in the negative group, at 31.2%. After accounting for the observation period, the positive group also had a 4.3 times higher risk of relapse.

Among patients from the eight South Korean hospitals, the relapse rate over the entire follow-up period was also significantly higher in the positive group than in the negative group, at 87.5% and 34.1%, respectively. By contrast, there was no significant difference among patients in the UK: 47.1% in the positive group and 38.5% in the negative group. Taking into account that patients in the UK group had used oral steroids for a relatively longer period, the researchers conducted a separate analysis of patients who had used oral steroids or immunosuppressants for less than six months. In this analysis, the positive group had a significantly higher risk of relapse.

An analysis combining all three patient groups found that the MOG-alpha3 antibody-positive group had about 2.7 times the relapse risk of the negative group. When the analysis was limited to patients who had received immunosuppressive treatment for less than six months, the risk was about 3.6 times higher. Both figures are adjusted hazard ratios.

The research team said that a negative result for MOG-alpha3 antibodies does not mean a patient will not relapse, but that antibody status could be used as an additional indicator when assessing relapse risk.

“This study shows that additional information for assessing a patient's risk of relapse can be obtained by determining which form of the MOG protein the MOG antibodies react to,” Professor Kim Seongmin said. “For patients who test positive for MOG-alpha3 antibodies, the findings could provide a basis for considering more active relapse-prevention treatment from the time of their first episode. We will conduct larger-scale prospective studies to examine whether the findings can help inform clinical practice and treatment planning.” The results were published in the latest issue of the international journal Neurology: Neuroimmunology & Neuroinflammation.

This content was produced with the assistance of AI translation services.