Different features between pediatric-onset and adult-onset patients who are seropositive for MOG-IgG: A multicenter study in South China

Chen, Lu; Chen, Chen; Zhong, Xiaonan; Sun, Xiaobo; Zhu, Haixia; Li, Xiaojing; Yang, Hui; Shu, Yaqing; Chang, Yanyu; Hu, Xueqiang; Liu, Zhengqi; Peng, Lisheng; Qiu, Wei

doi:10.1016/j.jneuroim.2018.05.014

Cited by 46 publications

(42 citation statements)

References 37 publications

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“…In adults, most patients have ON, (LE)TM, or both (either simultaneously or subsequently). 49 Despite these apparent phenotypical differences, we did not find differences in HLA allele frequencies when comparing subgroups regarding age (child vs adult), disease course (mono-vs multiphasic), and clinical presentation (opticospinal vs non-opticospinal and ADEM vs non-ADEM), neither after exclusion of rare MOGAD presentations. This again supports our main finding regarding the absence of HLA association in MOGAD, with also the absence of HLA association in distinctive MOGAD subgroups.…”

Section: Discussioncontrasting

confidence: 60%

HLA association in MOG-IgG– and AQP4-IgG–related disorders of the CNS in the Dutch population

Bruijstens

Wong

Pelt

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases.MethodsBlood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG–seropositive and 42 AQP4-IgG–seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors.ResultsNo significant HLA association was found in MOG-IgG–seropositive patients. The AQP4-IgG–seropositive patients had a significant higher frequency of HLA-A*01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707–5.863, p after correction [pc] = 0.0045), HLA-B*08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513–8.643, pc < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495–5.042, pc = 0.0199) compared with controls.ConclusionsThe present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG–positive NMOSD. The strong positive association with HLA-A*01, -B*08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG–positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders.

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Section: Discussioncontrasting

confidence: 60%

HLA association in MOG-IgG– and AQP4-IgG–related disorders of the CNS in the Dutch population

Bruijstens

Wong

Pelt

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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“…A short TM occurred in 14% of patients >45 years, but was rarely described in younger patients. The age-dependent clinical presentation was confirmed in a further study, with a predominance of ON found in adult onset MOG antibody-associated disorders, compared to a predominance of ADEM-like patterns in children as well as better recovery from neurological symptoms in children ( 53 ). The second largest study to include MOG antibody positive patients supported ON/TM as the main manifestations, given they represented clinical onset in over 90% of adult patients ( 49 ).…”

Section: Clinical Presentation and Prognosis Of Mog Antibody-associatmentioning

confidence: 55%

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders: Toward a New Spectrum of Inflammatory Demyelinating CNS Disorders?

Berger

2018

Front. Immunol.

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Inflammatory demyelinating CNS syndromes include, besides their most common entity multiple sclerosis (MS), several different diseases of either monophasic or recurrent character—including neuromyelitis optica spectrum disorders (NMOSDs) and acute disseminated encephalomyelitis (ADEM). Early diagnostic differentiation is crucial for devising individual treatment strategies. However, due to overlapping clinical and paraclinical features diagnosis at the first demyelinating event is not always possible. A multiplicity of potential biological markers that could discriminate the different diseases was studied. As the use of autoantibodies in patient management of other autoimmune diseases, is well-established and evidence for the critical involvement of B cells/antibodies in disease pathogenesis in inflammatory demyelinating CNS syndromes increases, antibodies seem to be valuable diagnostic tools. Since the detection of antibodies against aquaporin-4 (AQP-4), the understanding of immunopathogenesis and diagnostic management of NMOSDs has dramatically changed. However, for most inflammatory demyelinating CNS syndromes, a potential antigen target is still not known. A further extensively studied possible target structure is myelin oligodendrocyte glycoprotein (MOG), found at the outermost surface of myelin sheaths and oligodendrocyte membranes. With detection methods using cell-based assays with full-length, conformationally correct MOG, antibodies have been described in early studies with a subgroup of patients with ADEM. Recently, a humoral immune reaction against MOG has been found not only in monophasic diseases, but also in recurrent non-MS diseases, particularly in pediatric patients. This review presents the findings regarding MOG antibodies as potential biological markers in discriminating between these different demyelinating CNS diseases, and discusses recent developments, clinical implementations, and data on immunopathogenesis of MOG antibody-associated disorders.

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“…All patients had clinical manifestations related to central nervous system (CNS) demyelinating diseases and were tested for serum MOG-IgG and AQP4-IgG by a cell-based assay (CBA), as described previously. 8 In total, 186 patients were seropositive for MOG-IgG, and 71 of them had no peripheral blood specimens stored after the test. A total of 115 MOG-IgG-positive patients were collected and followed up every 2 months in this study.…”

Section: Methodsmentioning

confidence: 99%

“… 7 Clinical phenotypes at onset are more frequently characterised by encephalopathy in paediatric patients with MOGADs, while older patients often exhibit ON. 8 9 MOG-IgG titres are also significantly higher in paediatric patients than in adults. 10 11 The differences in multiple features among patients with paediatric-onset and adult-onset MOGADs suggest different underlying pathogenetic mechanisms, which are still unclear.…”

Section: Introductionmentioning

confidence: 91%

Myelin oligodendrocyte glycoprotein-associated disorders are associated with HLA subtypes in a Chinese paediatric-onset cohort

Sun

Wang

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectiveMyelin oligodendrocyte glycoprotein-associated disorders (MOGADs) are a rare new neurological autoimmune disease with unclear pathogenesis. Since a linkage of the disease to the human leucocyte antigen (HLA) has not been shown, we here investigated whether MOGAD is associated with the HLA locus.MethodsHLA genotypes of 95 patients with MOGADs, assessed between 2016 and 2018 from three academic centres, were compared with 481 healthy Chinese Han individuals. Patients with MOGADs included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for IgG targeting the myelin oligodendrocyte glycoprotein (MOG).ResultsPaediatric-onset MOGAD was associated with the DQB1*05:02–DRB1*16:02 alleles (OR=2.43; OR=3.28) or haplotype (OR=2.84) of HLA class II genes. The prevalence of these genotypes in patients with paediatric-onset MOGAD was significantly higher than healthy controls (padj=0.0154; padj=0.0221; padj=0.0331). By contrast, adult-onset MOGAD was not associated with any HLA genotype. Clinically, patients with the DQB1*05:02–DRB1*16:02 haplotype exhibited significantly higher expanded disability status scale scores at onset (p=0.004) and were more likely to undergo a disease relapse (p=0.030). HLA–peptide binding prediction algorithms and computational docking analysis provided supporting evidence for the close relationship between the MOG peptide subunit and DQB1*05:02 allele. In vitro results indicated that site-specific mutations of the predicted target sequence reduced the antigen–antibody binding, especially in the paediatric-onset group with DQB1*05:02 allele.ConclusionsThis study demonstrates a possible association between specific HLA class II alleles and paediatric-onset MOGAD, providing evidence for the conjecture that different aetiology and pathogenesis likely underlie paediatric-onset and adult-onset cases of MOGAD.

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Different features between pediatric-onset and adult-onset patients who are seropositive for MOG-IgG: A multicenter study in South China

Cited by 46 publications

References 37 publications

HLA association in MOG-IgG– and AQP4-IgG–related disorders of the CNS in the Dutch population

HLA association in MOG-IgG– and AQP4-IgG–related disorders of the CNS in the Dutch population

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders: Toward a New Spectrum of Inflammatory Demyelinating CNS Disorders?

Myelin oligodendrocyte glycoprotein-associated disorders are associated with HLA subtypes in a Chinese paediatric-onset cohort

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