Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD

We characterized a unique group of patients with neuromyelitis optica spectrum disorder(NMOSD) who carried autoantibodies of aquaporin-4(AQP4) and myelin-oligodendrocyte glycoprotein(MOG). Among the 125 NMOSD patients, 10(8.0%) were AQP4- and MOG-ab double positive, and 14(11.2%) were MOG-ab single positive. The double-positive patients had a multiphase disease course with a high annual relapse rate(P=0.0431), and severe residual disability(P<0.0001). Of the double-positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal magnetic resonance imaging(MRI), pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. In contrast, patients with only MOG-ab had a higher ratio of monophasic disease course and mild residual disability. Spinal cord MRI illustrated multifocal cord lesions with mild edema, and brain MRIs showed more lesions around lateral ventricles. NMOSD patients carrying both autoantibodies to AQP4 and MOG existed and exhibited combined features of prototypic NMO and relapsing-remitting form of MS, whereas NMOSD with antibodies to MOG only exhibited an "intermediate" phenotype between NMOSD and MS. Our study suggests that antibodies against MOG might be pathogenic in NMOSD patients and that determination of anti-MOG antibodies maybe instructive for management of NMOSD patients.

Experimental models of neuromyelitis optica: current status, challenges and future directions

Neuromyelitis optica （NMO） is a recurrent inflammatory disease that predominantly attacks the optic nerves and spinal cord. NMO-IgG, the specific autoantibody present in the vast majority of NMO patients, targets the astrocytic water channel protein aquaporin 4 （AQP4）, and differentiates NMO from multiple sclerosis. The growing clinical and research interest in NMO makes it urgent to produce an animal model of NMO. The pathogenic effect of anti-AQP4 antibodies derived from the serum of patients paves the way to generating an experimental model based on the anti-AQP4-mediated astrocyte damage. In this review, we discuss the contribution of experimental models to the understanding of the pathogenesis of the disease and drug development. Key questions raised by the existing models are also discussed.

Group 2 innate lymphoid cells resolve neuroinflammation following cerebral ischaemia

Background Acute brain ischaemia elicits pronounced inflammation,which aggravates neural injury.However,the mechanisms governing the resolution of acute neuroinflammation remain poorly understood.In contrast to regulatory T and B cells,group 2 innate lymphoid cells(ILC2s)are immunoregulatory cells that can be swiftly mobilised without antigen presentation;whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown.Methods Leveraging brain tissues from patients who had an ischaemic stroke and a mouse model of focal ischaemia,we characterised the presence and cytokine release of brain-infiltrating ILC2s.The impact of ILC2s on neural injury was evaluated through antibody depletion and ILC2 adoptive transfer experiments.Using Rag2−/−γc−/−mice receiving passive transfer of IL-4−/−ILC2s,we further assessed the contribution of interleukin(IL)-4,produced by ILC2s,in ischaemic brain injury.Results We demonstrate that ILC2s accumulate in the areas surrounding the infarct in brain tissues of patients with cerebral ischaemia,as well as in mice subjected to focal cerebral ischaemia.Oligodendrocytes were a major source of IL-33,which contributed to ILC2s mobilisation.Adoptive transfer and expansion of ILC2s reduced brain infarction.Importantly,brain-infiltrating ILC2s reduced the magnitude of stroke injury severity through the production of IL-4.Conclusions Our findings revealed that brain ischaemia mobilises ILC2s to curb neuroinflammation and brain injury,expanding the current understanding of inflammatory networks following stroke.