Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study

Abstract

Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as a potential biomarker in patients with inflammatory demyelinating diseases of the central nervous system. We here compare the clinical and laboratory findings observed in a cohort of MOG-Ab seropositive and seronegative cases and describe IgG subclass analysis results. Consecutive serum samples referred to Verona University Neuropathology Laboratory for aquaporin-4 (AQP4)-Ab and/or MOG-Ab testing were analysed between March 2014 and May 2017. The presence of AQP4-Ab was determined using a cell-based assay. A live cell immunofluorescence assay was used for the detection of MOG-IgG and IgG subclass analysis. Among 454 analysed samples, 29 were excluded due to AQP4-Ab positivity or to the final demonstration of a disorder not compatible with MOG-Ab. We obtained clinical data in 154 out of 425 cases. Of these, 22 subjects resulted MOG-Ab positive. MOG-Ab positive patients were mainly characterised by the involvement of the optic nerve and/or spinal cord. Half of the cases presented relapses and the recovery was usually partial. Brain MRI was heterogeneous while short lesions were the prevalent observation on spinal cord MRI. MOG-Ab titre usually decreased in non-relapsing cases. In all MOG-IgG positive cases, we observed IgG1 antibodies, which were predominant in most subjects. IgG2 (5/22), IgG3 (9/22) and IgG4 (3/22) antibodies were also detectable. We confirm that MOG-Ab-related syndromes have distinct features in the spectrum of demyelinating conditions, and we describe the possible role of the different IgG subclasses in this condition.

Keywords: Acute disseminated encephalomyelitis (ADEM); Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies; Multiple sclerosis (MS); Myelitis; Neuromyelitis optica spectrum disorders (NMOSD); Optic neuritis.

Fig. 1

Patient cohort. Of the 454 serum samples that were referred to the laboratory of Neuropathology, University Hospital of Verona for the analysis of AQP4-Ab/MOG-Ab between March 2014 and May 2017, nine resulted AQP4-Ab positive and MOG-Ab negative and were excluded from further analysis. We also excluded 20 subjects that received a final diagnosis of non-inflammatory neurological conditions or other defined inflammatory disorders. In 154 out of 425 included subjects, the clinical and paraclinical data had been well-characterised. Among the final cohort, 132 patients resulted as MOG-Ab negative and 22 MOG-Ab positive, at different titres (1:160 in 5 cases, 1:320 in 4, 1:640 in 7, 1:1280 in 2, 1:2560 in 2, 1:10,240 in 1 and 1:81,920 in 1 case). An additional group of 50 control samples were also tested for MOG-Ab, and resulted negative

Fig. 2

Brain radiological findings. One isolated frontal lesion (a), followed by monolateral optic nerve (b) and thalamic involvement (c) and subsequently by chiasmatic and monolateral optic tract damage (d, e) are shown in case 18. Non-specific white matter lesions were observed at onset in case 13 (f, g) while typical white matter lesions are shown in the patient with MS diagnosis (case 22, h)