Anti-MOG antibodies are rare in patients with a first demyelinating flare suggestive of multiple sclerosis

From left to right, Georgina Arrambide, Carmen Espejo, Álvaro Cobo-Calvo and Javier Villacieros-Álvarez, lead authors of the study.

Only 2.7% of the cohort analyzed had these antibodies, but they are very relevant for diagnosing and differentiating multiple sclerosis from the disease associated with anti-MOG antibodies (MOGAD).

A study recommends limiting the determination of anti-MOG antibodies to those patients who also present features compatible with MOGAD disease, in order to improve case detection and differentiate it from multiple sclerosis. The work has been led by researchers Álvaro Cobo-Calvo and Javier Villacieros-Álvarez from the Multiple Sclerosis Center of Catalonia (Cemcat), directed by Xavier Montalban, and the Vall d'Hebron Research Institute (VHIR), which are part of the Vall d'Hebron Campus. Dr. Montalban also directs the Neurology Service of the Vall d'Hebron University Hospital, as well as the Clinical Neuroimmunology research group at VHIR.

Despite having some similar clinical and radiological features, in recent years, MOGAD has been recognized as a different disease from multiple sclerosis or neuromyelitis optica. All three are classified within the group of so-called demyelinating diseases, where the immune system's attack on the myelin covering the neurons of the central nervous system (spinal cord and brain) causes dysfunction, mainly visual and motor. However, their treatment, prognosis, and evolution are different, therefore, it is essential to distinguish between them through a good differential diagnosis.

"Unlike multiple sclerosis, which does not have it, for MOGAD there is a specific marker that helps diagnose cases. They are the anti-MOG antibodies," explains Dr. Javier Villacieros-Álvarez, neurologist and predoctoral researcher at Cemcat and of the Clinical Neuroimmunology group at VHIR. "However, the prevalence of these antibodies, i.e., the number of patients who present them at the onset of the first outbreak with neurological symptoms, is unknown.

Villacieros-Álvarez is the first author of an article published in the journal Annals of Neurology, whose aim is to determine which patients with initial symptoms of demyelination need to be tested for anti-MOG antibodies. " In this study, we also wanted to see whether the presence of antibodies modifies the clinical manifestations, the appearance of outbreaks, the evolution of lesions, disability and prognosis," adds Dr. Álvaro Cobo-Calvo, leader of the study, neurologist at Cemcat and at the Neurology Service of the Vall d'Hebron University Hospital.

The work analyzes serum samples from 630 adult patients, collected during the six months following the onset of the first demyelinating event suggestive of multiple sclerosis. "The determination of the antibodies was carried out using a live cell-based technique. This technique has demonstrated a high specificity of up to 98%, which allows us to reliably diagnose cases of MOGAD," says Dr. Carmen Espejo, principal investigator at Cemcat and of the Clinical Neuroimmunology group at VHIR, and co-corresponding author of the article.

According to the results, only 17 of the 630 patients had anti-MOG antibodies. "This represents 2.7% of the cohort. Therefore, it seems that the presence of antibodies is infrequent in patients with a first demyelinating episode compatible with multiple sclerosis," notes Cobo-Calvo. As regards symptoms, many positive patients present optic neuritis, a condition that appears when inflammation causes damage to the optic nerve. In contrast, the number of brain lesions, as assessed by magnetic resonance imaging, is higher in patients without antibodies. Finally, in the cerebrospinal fluid of patients with anti-MOG antibodies, the researchers did not detect oligoclonal bands, a biomarker of inflammation in the central nervous system that is used for the diagnosis of multiple sclerosis.

"Taken together, our study demonstrates that anti-MOG antibodies are rare in persons of adult age presenting with a first demyelinating event suggestive of multiple sclerosis. However, following the results, we recommend determining their presence in those patients with symptoms of optic neuritis and absence of oligoclonal bands in cerebrospinal fluid, in order to identify cases of MOGAD. Especially when magnetic resonance imaging does not allow us to conclude a clear diagnosis of multiple sclerosis," Villacieros-Álvarez concludes. "The ability to be able to diagnose and differentiate both diseases as early as possible is fundamental to impact and stop the evolution of the disease before irreversible damage occurs."

Reference article
Villacieros-Álvarez J, Espejo C, Arrambide G, Castillo M, Carbonell-Mirabent P, Rodriguez M, Bollo L, Castilló J, Comabella M, Galán I, Midaglia L, Mongay N, Nos C, Rio J, Rodríguez-Acevedo B, Sastre-Garriga J, Tur C, Vidal-Jordana A, Vilaseca A, Zabalza A, Auger C, Rovira A, Montalban X, Tintoré M, Cobo-Calvo Á. MOG antibodies in adults with a first demyelinating event suggestive of multiple sclerosis. Ann Neurol. 2023 Sep 14.