| Objective and Backgroud:NMO(Neuromyelitis Optica,NMO)has been considered as a rare variant of MS(Multiple Sclerosis,MS)for many years.The discovery of AQP4-Ab(Aquaporin 4 antibody,AQP4-Ab)has promoted great progress on study of NMO in the past decade.Serum AQP4 antibody has been instrumental in the diagnosis of NMO.Although several methodologies have been developed to AQP4 antibody with large sample size in multiple centers,there are a still 10-25%of patients have no detectable AQP4-antibody.This observation not only posse challenge for diagnosis of NMO but also raises important questions as what are the immune target in NMO patients without antibodies to AQP4.MOG is considered the most promising candidate autoantigen in MS and is the only antigen that initiate both demyelinating autoantibody response and T cell response in Experimental autoimmune encephalomyelitis(EAE).However,whether MOG-antibody exists in NMO patients,whether MOG-antibody indicates another clinical phenotype are the questions need to be discussed.To solve above questions,we scan the MOG antibody in NMO patients.We summarize the characteristics in each group divided according to the AQP4 and MOG antibody testing results.The successive discovery of two autoimmune antibody specific to AQP4 and MOG indicated us the importance of humoral immune in pathogenesis of NMO.The activation of B cell and the production of specific antibodies are depended on the Th cell.Recently,follicular T helper cell has become a hot-spot on researching Th cells.It also arising our interest in the changes of Tfh cell in NMOSD patients.Therefore,we monitored the Tfh cell to find the association between Tfh and NMOSD.Method:For the study of MOG-antibody,we included 125 NMOSD.91 RRMS,45 Health Control,45 patients with miscellaneous neurological diseases(acute cerebral stroke 17,epilepsy 10,encephalitis 5,Myasthenia gravis 5,Guillain-Barre syndrome 3,and paraneoplastic syndrome 5).125 NMOSD patients were divided into three groups according to the testing-results of MOG-antibody and AQP4-antibody.Comparisons between groups on clinical,MRI and lab results revealed the possibility for MOG indicate another phenotype of NMOSD.For the study of Tfh cells,we included 35 NMOSD patients(24 remitting,11 relapse),20 MS patients(10 remitting,10 relapse)and 20 Health Control.We followed-up 6 patients responding to the glucocorticoid.We further studied the changes of Tfh and related cytokines to find the association between the follicular helper T cells and the NMOSD.Results:·The(MOG+AQP4)antibody positive patients had a higher ratio of multiphasic disease course[(MOG+AQP4)antibody positive positive vs AQP4-Ab positive vs MOG-Ab positive=100%vs 96%vs 57%,P<0.0001),higher annual relapse rate[AQP4-Ab positive vs MOG-Ab positive vs(MOG+AQP4)antibody positive-1.0±0.1 vs 1.2 ± 0.2 vs 1.7 ± 0.4,P=0.0431],and more severe residual disability[(MOG+AQP4)antibody positive vs AQP4-Ab positive,6.8 ± 0.5 vs 4.3 ± 0.6,P=0.0161;AQP4-Ab positive vs MOG-Ab positive,4.3 ± 0.6 vs 1.5 ± 0.4,P=0.0083)],MS-like brain lesions,multifocal regions on spinal MRI,more severe edematous,pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves.·Patients with only MOG-Ab have a higher ratio of monophasic disease course,mild residual disability,more brain lesions around lateral ventricles and multifocal cord lesions with mild edema,barely accompanied with nerve fiber layer thinning and optic nerves atrophy.·Augmented circulating Tfh cells and were found in NMOSD patients.(7.05 ± 1.97%vs 5.22 ± 1.46%,P=0.0008;NMOSD vs HC = 7.05 ± 1.97%vs 5.14 ± 1.33%,P=0.0005).Augmented IL-6 and IL-21 were found in NMOSD patients.·Augmented circulating Tfh cells and were found in relapsing NMOSD(Relapsing vs Remitting=8.56 ± 1.82%vs 6.35 ± 1.64%,P = 0.0034;Remitting vs HC 6.35 ±1.64%vs 5.13 ± 1.33%P=0.0196).Augmented IL-6、IL-21、TNF-α、IL-17 were found in relapsing NMOSD than other two groups.·Glucocorticoid treatment decreased the proportion of Tfh cell in NMOSD.Decreased IL-21、IL-6、TNF-α and IL-17 were found in the after-treatment group.·No correlations were found between AQP4-antibody level and Tfh cell counts.Conclusion:Significant differences were found in MOG-antibody positive group.The features of double-positive group tend to combine the features of each single-positive group together.This revealed us the diverse pathogenesis of MOG-antibody and the clinical significance of testing MOG-antibody.The significantly increasing Tfh cell revealed the close associations between the Tfh cell and disease activity.However,whether Tfh could be the biomarker of disease activities need further studies with big sample size. |
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