Anti-MOG Antibodies Lack Utility in Children With Demyelinating Syndromes

By Will Boggs MD

September 27, 2019

NEW YORK (Reuters Health) - Contrary to earlier suggestions, anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies provide little guidance for managing treatment in children with demyelinating syndromes, according to new research.

"We found that while anti-MOG-antibody persistence is associated with an increased risk of recurrence, still the majority in whom antibodies persist will not experience recurrence (at least for several years of follow-up) and that, conversely, recurrence of disease can occur also in children whose anti-MOG antibodies do not persist," Dr. Amit Bar-Or of the University of Pennsylvania, in Philadelphia, told Reuters Health by email.

Some researchers have suggested that persistent anti-MOG-antibody seropositivity following acquired demyelinating syndromes (ADS) is associated with relapsing disease in both children and adults, whereas the studies to date indicate that the relapse risk might be overestimated.

Dr. Bar-Or and colleagues evaluated long-term clinical and imaging outcomes and their association with serial serum MOG antibody measurements in 274 children with ADS, who were recruited through the Canadian Pediatric Demyelinating Disease Study between 2004 and 2017.

Overall, 84 children (30.7%) had detectable MOG antibodies, 179 (65.3%) tested negative, and 11 (4.0%) had borderline results.

Anti-MOG antibodies were associated with a higher number of lesions in children younger than 11 years, but with fewer focal lesions in older children, the researchers report in JAMA Neurology, online September 23.

During follow-up of 216 children with samples available more than one year after baseline, 137 (98.6%) of 139 who were negative at presentation remained negative in all subsequent examinations.

Among the 67 children positive for anti-MOG antibodies at baseline, 24 (36%) remained persistently positive, 5 (7%) fluctuated between positive and negative status and 38 (57%) became seronegative.

During follow-up, 66 children met diagnostic criteria for multiple sclerosis (MS), 11 were diagnosed as having a relapsing non-MS disease, one as having AQP4-positive neuromyelitis optica spectrum disorder, and 196 as having a monophasic course of ADS.

Excluding children who met diagnostic criteria for MS, the occurrence of clinical relapses was significantly more common among anti-MOG-antibody-positive children (9/71, 13%) than among antibody-negative children (2/121, 2%).

A quarter of anti-MOG-antibody-positive children (5/20) who presented with monofocal optic neuritis and normal findings on brain MRI had subsequent clinical relapses, compared with none of the 17 anti-MOG antibody-negative children with the same presentation.

Similarly, among children presenting with acute disseminated encephalomyelitis, clinical relapses occurred in 9% (3/32) of seropositive children versus 3% (1/30) of seronegative children.

Among the 16 children who were positive for anti-MOG antibodies at presentation who experienced clinical relapses, nine were persistently seropositive, two had fluctuating serologic status, and five converted to seronegative status.

"Making decisions about who to treat with chronic immune therapy after an initial episode vs. who not to treat is unfortunately not easily based on anti-MOG-antibody persistence," Dr. Bar-Or said.

"Most children will remain monophasic regardless of anti-MOG antibody status," he said. "One should avoid a 'blanket' approach of placing all children who present with anti-MOG antibodies on chronic immune therapy, including those with persistence of anti-MOG antibodies. Proactive follow-up including serial MRIs at reasonable intervals would provide the best approach to determining who does or does not have recurrent disease so that treatment can be discussed and provided to those who will most need it and not to those who will not."

"More work is needed to understand actual roles of anti-MOG antibodies in pathophysiology," Dr. Bar-Or said. "For example, are they different across patients and can particular features of the antibodies be defined that better predict propensity for chronic/recurrent disease versus monophasic disease?"

Dr. Kevin Rostasy from Witten/Herdecke University, in Datteln, Germany, recently reviewed MOG spectrum disorders and the role of anti-MOG antibodies in clinical practice. He told Reuters Health by email, "The optimal treatment of children with MOG antibodies still needs to be determined. It is a great step forward that the American colleagues now recognize that this disease is a clinical reality."

"MOG antibodies speak against MS," he said. This is "very reassuring for parents, and the prognosis of MOG-antibody-associated diseases is good in the majority of children."

"Unfortunately, the study did not take into account the role and possible prognostic value of MOG-antibody titers over time in serum," Dr. Rostasy said.


JAMA Neurol 2019.