Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children

Abstract

Objective: To determine whether myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) were predictive of a demyelination phenotype in children presenting with acquired demyelinating syndrome (ADS).

Method: Sixty-five children with a first episode of ADS (12 acute disseminated encephalomyelitis, 24 optic neuritis, 18 transverse myelitis, 11 other clinically isolated syndrome) were identified from 2 national demyelination programs in the United Kingdom and France. Acute serum samples were tested for MOG-Abs by cell-based assay. Antibodies were used to predict diagnosis of multiple sclerosis (MS) at 1 year.

Results: Twenty-three of 65 (35%) children had MOG-Abs. Antibody-positive and antibody-negative patients were not clinically different at presentation, but identification of MOG-Abs predicted a non-MS course at 1-year follow-up: only 2/23 (9%) MOG-Ab-positive patients were diagnosed with MS compared to 16/42 (38%) MOG-Ab-negative patients (p = 0.019, Fisher exact test). Antibody positivity at outset was a useful predictor for a non-MS disease course, with a positive predictive value of 91% (95% confidence interval [CI] 72-99), negative predictive value of 38% (95% CI 24-54), positive likelihood ratio of 4.02 (CI 1.0-15.4), and odds ratio of 6.5 (CI 1.3-31.3).

Conclusions: MOG-Abs are found at presentation in 35% of patients with childhood ADS, across a range of demyelinating disorders. Antibody positivity can be useful in predicting a non-MS disease course at onset.

Figure 1. Full-length MOG cell-based assay using a serum dilution of 1:160 as a cutoff for positivity (red line in both plots)

(A) Myelin olidgodendrocyte glycoprotein antibodies (MOG-Abs) were detected in a range of childhood demyelination syndromes but not in aquaporin-4 (AQP4)-Ab–positive neuromyelitis optica patients (0/100) or adults with multiple sclerosis (MS) (0/100). There was no correlation between MOG-Ab titer at onset and acquired demyelinating syndrome phenotype (A) or patient age (B). ADEM = acute disseminated encephalomyelitis; CIS = clinically isolated syndrome; ON = optic neuritis; TM = transverse myelitis.

Figure 2. Summary of the utility of MOG-Abs and OCB testing in predicting pediatric disease course at onset compared to clinical follow-up at 1 year

Following testing with either myelin olidgodendrocyte glycoprotein antibody (MOG-Ab) or oligoclonal blands (OCBs), the additional testing of the respective other is represented by arrows to the respective outcomes. A MOG-Ab–positive test predicted a non–multiple sclerosis (MS) diagnosis, whereas OCB positivity was highly predictive of MS. Eleven of 15 OCB- positive patients developed MS (73%), whereas 11 of 14 OCB-positive and MOG-Abs–negative patients developed MS (79%). The one MOG-Ab–positive and OCB-positive patient did not have MS, and all MOG-Ab–positive and OCB-negative cases had a non-MS course, compared to 91% if only OCB was negative. Of the 14 patients not tested for intrathecal OCBs, 7 patients tested positive for MOG-Ab; 2 patients from the antibody-positive and 2 from the antibody-negative groups had a diagnosis of MS at 1-year follow-up. ADEM = acute disseminated encephalomyelitis; CIS = clinically isolated syndrome; N/D = not done; ON = optic neuritis; TM = transverse myelitis.

Figure 3. Two of 23 MOG-Ab–positive patients were diagnosed with MS compared to 16/42 MOG-Ab–negative patients (p = 0.02, Fisher exact test)

As myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) were only tested retrospectively, identification of the antibodies did not influence the final diagnosis. One hundred adult patients with multiple sclerosis (MS) and 100 adults with aquaporin-4 (AQP4)-Ab–positive neuromyelitis optica were all MOG-Ab negative. ADEM = acute disseminated encephalomyelitis; CIS = clinically isolated syndrome; ON = optic neuritis; TM = transverse myelitis.