Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses

Gontika, Maria P.; Anagnostouli, Maria C.

doi:https://doi.org/10.1155/2018/8487471

Multiple Sclerosis International

On this page

Abstract Introduction Discussion Conclusions Abbreviations Conflicts of Interest References Copyright Related Articles

Review Article | Open Access

Volume 2018 | Article ID 8487471 | https://doi.org/10.1155/2018/8487471

Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses

Maria P. Gontika¹and Maria C. Anagnostouli^1,2

Academic Editor: Mauro Zaffaroni

Received17 Jul 2018

Revised19 Sept 2018

Accepted07 Nov 2018

Published22 Nov 2018

Abstract

Early-onset (pediatric and adolescent) multiple sclerosis (MS) is a well-established demyelinating disease that accounts for approximately 3-5% of all MS cases. Thus, identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response in such patients is of paramount importance. Myelin oligodendrocyte glycoprotein (MOG) has been regarded as a putative autoantigen and autoantibody target in patients with demyelinating diseases for almost three decades. However, recent studies have suggested that antibodies against MOG represent a distinct clinical entity of dominantly humoral profile, with a range of clinical phenotypes closely related to the age of onset, specific patterns of disease course, and responses to treatment. Furthermore, the major histocompatibility complex (MHC)—which has been regarded as the “gold standard” for attributing genetic burden in adult MS since the early 1970s—has also emerged as the primary genetic locus in early-onset MS, particularly with regard to the human leukocyte antigen (HLA) alleles DRB1⁎1501 and DRB1⁎0401. Recent studies have investigated the potential interactions among HLA, MOG, and environmental factors, demonstrating that early-onset MS is characterized by genetic, immunogenetic, immunological, and familial trait correlations. In this paper, we review recent evidence regarding HLA-genotyping and MOG antibodies—the two most important candidate biomarkers for early-onset MS—as well as their potential application in the diagnosis and treatment of MS.

1. Introduction

Multiple sclerosis (MS) is a chronic autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS), representing the most common cause of neurological disability among young adults. For decades, the pediatric and adolescent form of the disease constituted a controversial entity that often escaped diagnosis. Presently, early-onset (pediatric and adolescent) MS is a well-established demyelinating disease that accounts for approximately 3-5% of all MS cases [1–3].

Different mechanisms of demyelination, neurodegeneration, gliosis, and remyelination converge in various ways to create a unique clinical result for each patient with MS. Thus, identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response is of paramount importance. However, no studies to date have identified absolute surrogates for MS [4]. In this paper, we review recent evidence regarding human leukocyte antigen (HLA) genotyping and myelin oligodendrocyte glycoprotein (MOG) antibodies—the two most important candidate biomarkers for early-onset MS—as well as their potential application in the diagnosis and treatment of MS.

2. Main Text

2.1. MOG Antibody-Related Disorders: Phenotypical Spectrum, Prognosis, and Treatment

Although MOG comprises less than 0.05% of all CNS myelin proteins, it is localized on the outermost surface of the myelin sheath, making it an excellent antibody target [5]. The human antibodies (Abs) to MOG exhibit all the characteristics of pathogenic autoantibodies: they recognize MOG in its correct conformation, they are mostly of the complement fixing isotype IgG1, and they activate Ab-dependent cellular cytotoxicity, although their exact pathogenic role remains to be further clarified [5–7].

MOG antibodies are continually identified in a range of acquired demyelinating syndromes (ADS) in both adults and children. MOG antibodies are present in up to one-third of children with ADS, especially in patients who have experienced an acute demyelinating episode prior to the age of 10 years. Furthermore, previous studies have demonstrated a link between MOG antibodies and non-MS diagnoses [8–11].

While older reports provided controversial evidence, more recent studies have revealed that children with MOG antibodies can present with either a monophasic or multiphasic disease course (in up to 50% of cases), primarily depending on their age [9–14]. Previous research has indicated that patients with a monophasic disease course are more often younger and male. Moreover, in the majority of cases (50%), monophasic forms of the disease manifest as acute disseminated encephalomyelitis (ADEM), especially in patients under the age of 5 years [9, 12, 15, 16]. Other monophasic subtypes include monophasic neuromyelitis optica spectrum diseases (NMOSDs) accompanied by optic neuritis and/or transverse myelitis [9, 12, 17, 18], as well as clinically isolated syndromes [optic neuritis (ON), transverse myelitis (TM), cerebellitis, and brainstem disease], which present after puberty and do not confer risk factors for further MS-like episodes, such as positive oligoclonal bands (OCBs) or MS-like lesions on MRI [9, 10, 12, 16]. Interestingly, in patients with the monophasic subtype, anti-MOG titers tend to be transient and fall to undetected levels during the months following an acute episode [9, 12, 19]. In contrast, especially in older female patients with high and persistent MOG titers, different multiphasic subtypes have been identified, including multiphasic disseminated encephalomyelitis (MDEM); ADEM followed by relapsing episodes of ON (ADEM-ON); NMOSD; and relapsing, steroid-responsive ON [9, 12, 20–27]. Recently, MOG Abs have been detected in cases of NMDAR encephalitis, further expanding the phenotypic spectrum of the disorder [28, 29].

Only a very small proportion of both children and adults with MS present with MOG antibody seropositivity, possibly representing a distinct phenotype which could benefit from different treatment strategies. This is in accordance with biopsy findings in MOG antibody patients with acute demyelinating episodes, which reveal a lesion pattern similar to MS pattern II with demyelination and complement activation [9, 30–33]. Moreover, Hennes et al. suggested that a cutoff higher than previously anticipated (e.g., ≥1,280) can be used to increase the specificity for a non-MS disease course and facilitate the interpretation of MOG assay results [9].

The vast majority of recent studies suggest that persistently high-titer MOG Abs, but not their sole presence at onset, are associated with a high risk of relapse and that serial testing during and between clinical relapses could be reasonable for safe therapeutic decision-making, when attempting to predict the clinical course in MOG antibody positive patients [9, 11, 12, 34]. In general, patients with monophasic disease tend to exhibit more favorable outcomes (i.e., resolution of clinical and imaging abnormalities), which does not seem to be the case in patients with relapsing disease, who tend to exhibit a high relapse rate and progressive impairments [9, 12, 34, 35].

Paraclinical tests have also been associated with a distinct profile in patients with MOG antibody associated diseases. Cerebrospinal fluid (CSF) analysis in MOG antibody positive children is mandatory for detecting pleocytosis and the usual absence of OCBs (90% of cases), while double positivity for both MOG and anti-aquaporin 4 (AQP4) is rare in patients with NMOSD phenotypes and usually not statistically significantly different from healthy controls [8, 9, 12, 36]. MRI findings also vary among clinical phenotypes. In younger patients with an ADEM-like presentation, MRI findings are usually characterized by poorly demarcated and widespread lesions, sometimes with extensive myelin involvement including the conus. Such lesions exhibit no postcontrast enhancement and tend to resolve. In older patients, MRI findings can align with those of NMOSD, which is associated with extensive involvement of the optic nerves and periependymal areas as well as longitudinal extensive transverse myelitis (LETM). In such patients, lesions occasionally extend rostrally into the medulla and often the conus, although normal MRI findings are common in patients with pure relapsing ON [12, 16, 37]. The few MOG antibody seropositive children diagnosed with relapsing–remitting MS tend to exhibit a typical MS-like pattern with well demarcated periventricular and curved juxtacortical lesions involving U-fiber lesions, Dawson finger-type lesions, and short transverse myelitis [38].

In the acute phase, intravenous steroid treatment followed by per os tapering, intravenous immunoglobulin treatment, and plasmapheresis cycles appears to be associated with good responsiveness [12, 24, 37, 39]. However, the most effective treatments for relapsing disease remain to be clarified. Children with MOG antibody associated disorders generally did not benefit from the disease-modifying therapies commonly used in MS, in those rare cases that they have been employed, which also led to dramatic aggravation of symptoms in select cases [40–43]. B-cell-directed interventions (e.g., plasmapheresis and rituximab) have yielded positive results, along with certain immunosuppressive drugs (e.g., mycophenolate, azathioprine) [12, 44–46]. In their recent study of 102 children, Hacohen et al. reported that IV immunoglobulin maintenance therapy was the only intervention to significantly improve relapse rates and functional outcomes, expanding its well-known immunomodulatory effect in a probable dose-dependent manner [34].

2.2. HLA Alleles in Pediatric MS

Linkage studies in various populations have consistently demonstrated that the MHC and its polymorphisms represent the genetic locus most strongly linked to MS [47, 48]. In a recent collaborative European study, DRB11501 (split of DR2) exhibited the strongest association with MS, along with DRB10301 and DRB11301, while HLA-A0201 has been shown to confer protection against MS [49].

Numerous studies have verified the association between DRB115 and early-onset MS [50–52], supporting the notion that genetic contributions are fundamentally similar in both early-onset and adult MS. However, whether HLA-DRB11501 by itself lowers the age at MS onset remains controversial, with several studies indicating that both genetic and environmental epistatic interactions may play a role [53–71]. Several hypotheses have been proposed in an effort to explain this discrepancy. Ramagopalan et al. observed that only maternally transmitted DRB115 promotes lower age at MS onset, suggesting a possible parent of origin effect, while others have implicated relative fluctuations in vitamin D levels among different populations [72, 73].

In 2010, a remarkable DRB1-genotyping study in Australia became the first to demonstrate the significance of epistatic interactions at the HLA-DRB1 locus. Carriage of the DRB11501 risk allele was not significantly associated with age at onset, while the DRB10401 allele was associated with a reduced age at onset when combined with DRB11501 [74].

In our recent study in the Greek population, we proposed that the DRB103 allele may be associated with early-onset MS. However, further studies are required to verify this finding, as this allele has been associated not only with a presumably better MS prognosis, but also with NMO, a mainly humoral immunological entity [50].

In parallel with HLA studies, recent genome-wide association studies (GWAS) have provided evidence for more than 50 single-nucleotide polymorphisms (SNPs) of more modest effect that influence the risk of both adult MS and early-onset MS, further equalizing the genetic burden of these age groups [75] and suggesting possible clinical correlations [76]. In a 2017 study by Gianfrancesco et al., the authors analyzed 28 non-MHC mutations in 569 cases of early-onset MS. Despite the extensive literature regarding adult MS, they concluded that—while the generally observed higher burden did not reach statistical significance—the weighted genetic risk score of these mutations was significantly associated with pediatric-onset MS [77].

3. Discussion

Pediatric and adolescent MS is a well-defined clinical entity with established diagnostic criteria, whose early diagnosis and treatment may alter clinical outcomes in younger patients. In the context of the largely expanding therapeutic repertoire, the identification of genetic and antibody biomarkers may help guide diagnosis, predict disease course, and achieve targeted treatment. MOG antibodies and HLA alleles, either individually or via interactive mechanisms, have emerged as the two most promising candidates for such biomarkers.

MOG has been identified as a putative autoantigen and autoantibody target in patients with demyelination for almost three decades. However, only recently have cell-based assays (CBAs) and large-scale studies revealed its role in childhood and adolescent demyelination [23]. Earlier studies investigated MOG autoimmunity within the framework of specific demyelinating syndromes, including ADEM and pediatric MS, and while in ADEM cases the results were consistent, usually contradictory results were obtained in patients with CIS and an association with conversion to MS, especially before the introduction of CBAs [18, 78–90]. More recent evidence has demonstrated that antibodies against MOG may be associated with a clinical entity distinct from MS and AQP4-positive NMOSD [91–96]. This new entity, of dominantly humoral profile, is characterized by a range of clinical phenotypes closely related to the age of onset, with their own course, response to treatment, and prognosis, expanding the differential diagnostic work-up for patients with suspected demyelinating diseases. Thus, Hacohen et al. proposed a diagnostic algorithm for relapsing ADS in children, identifying five categories of relapsing DS (MS, anti-AQP4-positive NMOSD, MOG antibody associated disorders, and antibody-negative RDS) and highlighting the importance of anti-MOG testing in the differential diagnosis of MS [97]. Moreover, extended clinical and radiologic diagnostic criteria regarding the spectrum of MOG associated disorders have been recently proposed and although they could be adjusted on the basis of the evolving knowledge in this field, they could provide great assistance in everyday clinical practice [98–101].

In contrast, since its discovery and the early disease association studies of the 1970s, the MHC and its polymorphisms have represented the “gold standard” for attributing genetic burden in adult MS. Recently studies have further established the role of HLA-DRB11501 in pediatric and adolescent, while the roles of HLA-DRB10401 and HLA-DRB103 remain to be clarified. Furthermore, HLA genotype may interact with MOG and environmental factors, especially viruses, which may explain in part the clinical diversity of MOG antibody associated disorders. In particular, HLA-DRB10401, which appears to correlate with younger age at onset via epistatic interactions with HLA-DRB11501, also appears to bind with high affinity to MOG epitopes in both familial patients with MS and asymptomatic relatives. These findings indicate that humoral immune reactivity against MOG is partially under the control of certain HLA class II alleles [102–107]. This observation may be helpful in guiding therapy, as the HLA-DRB1∗0401 allele is associated with a greater risk of developing neutralizing antibodies against interferon beta (IFN-), which have been linked to poor therapeutic outcomes in adults [108]. Furthermore, in their recent breakthrough study, Morandi et al. investigated the potential interactions among MOG, HLA, and the Epstein–Barr virus (EBV), each of which is known to play a pathogenetic role in MS. Their findings demonstrated that EBV infection of B cells alters MOG processing, facilitating its cross-presentation to autoaggressive cytotoxic CD8 + T cells in an MHC-restricted manner, highlighting the interplay between genetic and biological factors in MS [109].

Abundant evidence supports the notion that MS is influenced by genetic, immunogenetic, immunological, and familial trait correlations. Table 1 [12, 50–71, 74, 98–101, 110–117] summarizes the available data regarding the distribution of HLA alleles and MRI findings for five demyelinating syndromes: clinically definite MS, AQP4-positive NMOSD, MOG antibody associated disorders, and antibody-negative ADEM. As indicated in the table, there is an obvious lack of information regarding HLA genotyping in pediatric and adolescent ADS, despite the fact that primary results demonstrate clear genetic diversity. We strongly believe that larger HLA-genotyping studies regarding early-onset demyelinating disorders are necessary. Such studies should be conducted in various ethnic groups in order to clarify, replicate, and expand the available evidence.

4. Conclusions

HLA alleles and MOG antibodies have emerged as two major biomarkers of pediatric and adolescent MS and related demyelinating disorders. Each of these putative biomarkers exhibits a separate correlation with MS pathogenesis, clinical course, and treatment responses, suggesting that these factors interact to influence MS phenotypes and outcomes, an assumption further supported by recent evidence. Thus, further large-scale studies regarding HLA and MOG antibodies are required to verify and expand our knowledge of early-onset MS and to determine the appropriate biomarkers for distinct clinical phenotypes.

Abbreviations

MS:	Multiple sclerosis
MHC:	Major histocompatibility complex
HLA:	Human leukocyte antigens
MOG:	Myelin oligodendrocyte glycoprotein
AQP4:	Aquaporin-4
Abs:	Antibodies
CSF:	Cerebrospinal fluid
OCBs:	Oligoclonal bands
ADS:	Acquired demyelinating syndromes
ADEM:	Acute disseminated encephalomyelitis
MDEM:	Multiphasic disseminated encephalomyelitis
ADEM-ON:	ADEM followed by optic neuritis
ON:	Optic neuritis
TM:	Transverse myelitis
NMO:	Neuromyelitis optica
NMOSD:	NMO spectrum diseases
GWAS:	Genome-wide association studies
SNPs:	Single-nucleotide polymorphisms
CBAs:	Cell-based assays
IFN-:	Interferon beta
CNS:	Central nervous system.

Conflicts of Interest

The authors declare that there are no conflicts of interesting regarding the publication of this article.

References

C. Renoux, S. Vukusic, and C. Confavreux, “The natural history of multiple sclerosis with childhood onset,” Clinical Neurology and Neurosurgery, vol. 110, no. 9, pp. 897–904, 2008.
View at: Publisher Site | Google Scholar
S. Venkateswaran and B. Banwell, “Pediatric multiple sclerosis,” The Neurologist, vol. 16, no. 2, pp. 92–105, 2010.
View at: Publisher Site | Google Scholar
M. L. B. Ferreira, M. Í. M. Machado, M. J. G. Dantas, Á. J. P. Moreira, and A. M. D. M. H. Souza, “Pediatric multiple sclerosis: Analysis of clinical and epidemiological aspects according to national MS society consensus 2007,” Arquivos de Neuro-Psiquiatria, vol. 66, no. 3 B, pp. 665–670, 2008.
View at: Publisher Site | Google Scholar
S. Katsavos and M. Anagnostouli, “Biomarkers in Multiple Sclerosis: An Up-to-Date Overview,” Multiple Sclerosis International, vol. 2013, Article ID 340508, 20 pages, 2013.
View at: Publisher Site | Google Scholar
A. Bar-Or, “The Immunology of Multiple Sclerosis,” Seminars in Neurology, vol. 28, no. 1, pp. 029–045, 2008.
View at: Publisher Site | Google Scholar
P. Peschl, K. Schanda, B. Zeka et al., “Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination,” Journal of Neuroinflammation, vol. 14, no. 1, 2017.
View at: Publisher Site | Google Scholar
P. Khare, D. K. Challa, S. C. Devanaboyina et al., “Myelin oligodendrocyte glycoprotein-specific antibodies from multiple sclerosis patients exacerbate disease in a humanized mouse model,” Journal of Autoimmunity, vol. 86, pp. 104–115, 2018.
View at: Publisher Site | Google Scholar
Y. Hacohen, M. Absoud, and K. Deiva, “Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children,” Neurology: Neuroimmunology & Neuroinflammation, vol. 2, no. 2, article e81, 2015.
View at: Publisher Site | Google Scholar
E.-M. Hennes, M. Baumann, K. Schanda et al., “Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome,” Neurology, vol. 89, no. 9, pp. 900–908, 2017.
View at: Publisher Site | Google Scholar
I. A. Ketelslegers, D. E. Van Pelt, S. Bryde et al., “Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort,” Multiple Sclerosis Journal, vol. 21, no. 12, pp. 1513–1520, 2015.
View at: Publisher Site | Google Scholar
S. Duignan, S. Wright, T. Rossor et al., “Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly specific in children with acquired demyelinating syndromes,” Developmental Medicine & Child Neurology, vol. 60, no. 9, pp. 958–962, 2018.
View at: Publisher Site | Google Scholar
E.-M. Hennes, M. Baumann, C. Lechner, and K. Rostásy, “MOG Spectrum Disorders and Role of MOG-Antibodies in Clinical Practice,” Neuropediatrics, vol. 49, no. 1, pp. 3–11, 2018.
View at: Publisher Site | Google Scholar
M. Reindl, F. Di Pauli, K. Rostásy, and T. Berger, “The spectrum of MOG autoantibody-associated demyelinating diseases,” Nature Reviews Neurology, vol. 9, no. 8, pp. 455–461, 2013.
View at: Publisher Site | Google Scholar
M. Reindl, “Clinical course of MOG antibody-associated recurrent demyelinating diseases,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 89, no. 2, pp. 118–118, 2018.
View at: Publisher Site | Google Scholar
M. Baumann, K. Sahin, C. Lechner et al., “Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 86, no. 3, pp. 265–272, 2015.
View at: Publisher Site | Google Scholar
C. Fernandez-Carbonell, D. Vargas-Lowy, A. Musallam et al., “Clinical and MRI phenotype of children with MOG antibodies,” Multiple Sclerosis Journal, vol. 22, no. 2, pp. 174–184, 2015.
View at: Publisher Site | Google Scholar
T. Kezuka, K. Tanaka, Y. Matsunaga et al., “Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders,” Neurology, vol. 83, no. 5, pp. 475-476, 2014.
View at: Publisher Site | Google Scholar
C. Lechner, M. Baumann, E.-M. Hennes et al., “Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 87, no. 8, pp. 897–905, 2016.
View at: Publisher Site | Google Scholar
A. K. Pröbstel, K. Dornmair, R. Bittner et al., “Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis,” Neurology, vol. 77, no. 6, pp. 580–588, 2011.
View at: Publisher Site | Google Scholar
M. Baumann, E.-M. Hennes, K. Schanda et al., “Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): Extending the spectrum of MOG antibody positive diseases,” Multiple Sclerosis Journal, vol. 22, no. 14, pp. 1821–1829, 2016.
View at: Publisher Site | Google Scholar
P. Huppke, K. Rostasy, M. Karenfort et al., “Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients,” Multiple Sclerosis Journal, vol. 19, no. 7, pp. 941–946, 2013.
View at: Publisher Site | Google Scholar
S. Jarius and B. Wildemann, “Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature,” Brain Pathology, vol. 23, no. 6, pp. 661–683, 2013.
View at: Publisher Site | Google Scholar
S. Ramanathan, R. C. Dale, and F. Brilot, “Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination,” Autoimmunity Reviews, vol. 15, no. 4, pp. 307–324, 2016.
View at: Publisher Site | Google Scholar
K. Rostasy, S. Mader, K. Schanda et al., “Anti–Myelin Oligodendrocyte Glycoprotein Antibodies in Pediatric Patients With Optic Neuritis,” JAMA Neurology, vol. 69, no. 6, 2012.
View at: Publisher Site | Google Scholar
F. di Pauli, S. Mader, K. Rostasy et al., “Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases,” Clinical Immunology, vol. 138, no. 3, pp. 247–254, 2011.
View at: Publisher Site | Google Scholar
K. Rostásy, S. Mader, E. M. Hennes et al., “Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica,” Multiple Sclerosis Journal, vol. 19, no. 8, pp. 1052–1059, 2013.
View at: Publisher Site | Google Scholar
P. Huppke, “MOG Antibodies in Pediatric Neurology,” Neuropediatrics, vol. 49, no. 1, pp. 1-2, 2018.
View at: Google Scholar
J. Zhou, W. Tan, S. E. Tan, J. Hu, Z. Chen, and K. Wang, “An unusual case of anti-MOG CNS demyelination with concomitant mild anti-NMDAR encephalitis,” Journal of Neuroimmunology, vol. 320, pp. 107–110, 2018.
View at: Publisher Site | Google Scholar
L. Zhou, J. ZhangBao, H. Li et al., “Cerebral cortical encephalitis followed by recurrent CNS demyelination in a patient with concomitant anti-MOG and anti-NMDA receptor antibodies,” Multiple Sclerosis and Related Disorders, vol. 18, pp. 90–92, 2017.
View at: Publisher Site | Google Scholar
M. Spadaro, L. A. Gerdes, M. Krumbholz et al., “Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis,” Neurology—Neuroimmunology Neuroinflammation, vol. 3, no. 5, article no. e257, 2016.
View at: Publisher Site | Google Scholar
M. Spadaro, L. A. Gerdes, M. C. Mayer et al., “Histopathology and clinical course of MOG-antibody-associated encephalomyelitis,” Annals of Clinical and Translational Neurology, vol. 2, no. 3, pp. 295–301, 2015.
View at: Publisher Site | Google Scholar
F. Di Pauli, R. Höftberger, M. Reindl et al., “Fulminant demyelinating encephalomyelitis,” Neurology - Neuroimmunology Neuroinflammation, vol. 2, no. 6, p. e175, 2015.
View at: Publisher Site | Google Scholar
S. Jarius, I. Metz, F. B. König et al., “Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in ‘pattern II multiple sclerosis’ and brain biopsy findings in a MOG-IgG-positive case,” Multiple Sclerosis Journal, vol. 22, no. 12, pp. 1541–1549, 2016.
View at: Publisher Site | Google Scholar
Y. Hacohen, Y. Y. Wong, C. Lechner et al., “Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease,” JAMA Neurology, vol. 75, no. 4, p. 478, 2018.
View at: Publisher Site | Google Scholar
M. Reindl, S. Jarius, K. Rostasy, and T. Berger, “Myelin oligodendrocyte glycoprotein antibodies: How clinically useful are they?” Current Opinion in Neurology, vol. 30, no. 3, pp. 295–301, 2017.
View at: Publisher Site | Google Scholar
R. Narayan, A. Simpson, K. Fritsche et al., “MOG antibody disease: A review of MOG antibody seropositive neuromyelitis optica spectrum disorder,” Multiple Sclerosis and Related Disorders, vol. 25, pp. 66–72, 2018.
View at: Publisher Site | Google Scholar
S. Ramanathan, K. Prelog, E. H. Barnes et al., “Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein mantibodies, aquaporin-4 antibodies, and multiple sclerosis,” Multiple Sclerosis, vol. 22, no. 4, pp. 470–482, 2016.
View at: Google Scholar
M. Baumann, A. Grams, T. Djurdjevic et al., “MRI of the first event in pediatric acquired demyelinating syndromes with antibodies to myelin oligodendrocyte glycoprotein,” Journal of Neurology, vol. 265, no. 4, pp. 845–855, 2018.
View at: Publisher Site | Google Scholar
S. Ramanathan, S. W. Reddel, A. Henderson et al., “Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis,” Neurology - Neuroimmunology Neuroinflammation, vol. 1, no. 4, p. e40, 2014.
View at: Publisher Site | Google Scholar
R. Marignier, A. C. Calvo, and S. Vukusic, “Neuromyelitis optica and neuromyelitis optica spectrum disorders,” Current Opinion in Neurology, vol. 30, no. 3, pp. 208–215, 2017.
View at: Publisher Site | Google Scholar
L. Azzopardi, A. L. Cox, C. L. McCarthy, J. L. Jones, and A. J. Coles, “Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series,” Journal of Neurology, vol. 263, no. 1, pp. 25–29, 2016.
View at: Publisher Site | Google Scholar
B. Wildemann, S. Jarius, A. Schwarz et al., “Failure of alemtuzumab therapy to control MOG encephalomyelitis,” Neurology, vol. 89, no. 2, pp. 207–209, 2017.
View at: Publisher Site | Google Scholar
S. Ramanathan, S. Mohammad, E. Tantsis et al., “Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 89, no. 2, pp. 127–137, 2018.
View at: Publisher Site | Google Scholar
P. Vermersch, T. Berger, R. Gold et al., “The clinical perspective: How to personalise treatment in MS and how may biomarkers including imaging contribute to this?” Multiple Sclerosis Journal, vol. 22, no. 2_suppl, pp. 18–33, 2016.
View at: Publisher Site | Google Scholar
R. C. Dale, F. Brilot, L. V. Duffy et al., “Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease,” Neurology, vol. 83, no. 2, pp. 142–150, 2014.
View at: Publisher Site | Google Scholar
A. Montcuquet, N. Collongues, C. Papeix et al., “NOMADMUS study group and the ObservatoireFrançais de la Scléroseen Plaques (OFSEP). Effectiveness of mycophenolatemofetil as first-line therapy in AQP4-IgG, MOG-IgG, and seronegative neuromyelitisoptica spectrum disorders,” Multiple Sclerosis, Article ID 1352458516678474, 2016.
View at: Google Scholar
S. V. Ramagopalan, D. A. Dyment, and G. C. Ebers, “Genetic epidemiology: the use of old and new tools for multiple sclerosis,” Trends in Neurosciences, vol. 31, no. 12, pp. 645–652, 2008.
View at: Publisher Site | Google Scholar
P. Stamatelos and M. Anagnostouli, “LA-Genotype in Multiple Sclerosis: The Role in Disease onset, Clinical Course, Cognitive Status and Response to Treatment: A Clear Step Towards Personalized Therapeutics,” Immunogenet, vol. 2, article 116, 2017.
View at: Google Scholar
S. Sawcer, G. Hellenthal, M. Pirinen et al., “Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis,” Nature, vol. 476, pp. 214–219, 2011.
View at: Google Scholar
M. C. Anagnostouli and A. Manouseli, “HLA-DRB1* Allele Frequencies in Pediatric, Adolescent and Adult-Onset Multiple Sclerosis Patients, in a Hellenic Sample. Evidence for New and Established Associations,” Journal of Multiple Sclerosis, vol. 01, no. 01, 2014.
View at: Publisher Site | Google Scholar
B. Banwell, A. Bar-Or, D. L. Arnold et al., “Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study,” The Lancet Neurology, vol. 10, no. 5, pp. 436–445, 2011.
View at: Google Scholar
G. Disanto, S. Magalhaes, A. E. Handel et al., “HLA-DRB1 confers increased risk of pediatric-onset MS in children with acquired demyelination,” Neurology, vol. 76, no. 9, pp. 781–786, 2011.
View at: Publisher Site | Google Scholar
T. Masterman, A. Ligers, T. Olsson, M. Andersson, O. Olerup, and J. Hillert, “HLA-DR15 is associated with lower age at onset in multiple sclerosis,” Annals of Neurology, vol. 48, no. 2, pp. 211–219, 2000.
View at: Publisher Site | Google Scholar
A. E. Hensiek, S. J. Sawcer, R. Feakes et al., “HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 72, no. 2, pp. 184–187, 2002.
View at: Publisher Site | Google Scholar
S. J. M. Weatherby, W. Thomson, L. Pepper et al., “HLA-DRB1 and disease outcome in multiple sclerosis,” Journal of Neurology, vol. 248, no. 4, pp. 304–310, 2001.
View at: Publisher Site | Google Scholar
C. Smestad, B. Brynedal, G. Jonasdottir et al., “The impact of HLA-A and -DRB1 on age at onset, disease course and severity in Scandinavian multiple sclerosis patients,” European Journal of Neurology, vol. 14, no. 8, pp. 835–840, 2007.
View at: Publisher Site | Google Scholar
K. Imrell, E. Greiner, J. Hillert, and T. Masterman, “HLA-DRB1*15 and cerebrospinal-fluid-specific oligoclonal immunoglobulin G bands lower age at attainment of important disease milestones in multiple sclerosis,” Journal of Neuroimmunology, vol. 210, no. 1-2, pp. 128–130, 2009.
View at: Publisher Site | Google Scholar
D. T. Okuda, R. Srinivasan, Oksenberg. J. R. et al., “Genotype-Phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures,” Brain, vol. 132, part 1, pp. 250–259, 2009.
View at: Google Scholar
R. Balnyte, D. Rastenyte, A. Vaitkus et al., “The importance of HLA DRB1 gene allele to clinical features and disability in patients with multiple sclerosis in Lithuania,” BMC Neurology, vol. 13, 2013.
View at: Google Scholar
S. Al-Shammri, R. F. Nelson, I. Al-Muzairi, and A. O. Akanji, “HLA determinants of susceptibility to multiple sclerosis in an Arabian Gulf population,” Multiple Sclerosis Journal, vol. 10, no. 4, pp. 381–386, 2016.
View at: Publisher Site | Google Scholar
O. I. Maslova, O. V. Bykova, M. R. Guseva et al., “Multiple sclerosis with early onset: pathogenesis, clinical characteristics, possibilities in the treatment of its pathogenesis,” Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, pp. 46–51, 2002.
View at: Google Scholar
A. Van Der Walt, J. Stankovich, M. Bahlo et al., “Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition,” Multiple Sclerosis Journal, vol. 17, no. 3, pp. 344–352, 2011.
View at: Publisher Site | Google Scholar
P. Villoslada, L. F. Barcellos, J. Rio et al., “The HLA locus and multiple sclerosis in Spain. Role in disease susceptibility, clinical course and response to interferon-β,” Journal of Neuroimmunology, vol. 130, no. 1-2, pp. 194–201, 2002.
View at: Publisher Site | Google Scholar
L. F. Barcellos, S. Sawcer, P. P. Ramsay et al., “Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis,” Human Molecular Genetics, vol. 15, no. 18, pp. 2813–2824, 2006.
View at: Publisher Site | Google Scholar
L. Barcellos, J. Oksenberg, A. Begovich et al., “HLA-DR2 Dose Effect on Susceptibility to Multiple Sclerosis and Influence on Disease Course,” American Journal of Human Genetics, vol. 72, no. 3, pp. 710–716, 2003.
View at: Publisher Site | Google Scholar
A. M. Silva, C. Pereira, A. Bettencourt et al., “The role of HLA-DRB1 alleles on susceptibility and outcome of a Portuguese Multiple Sclerosis population,” Journal of the Neurological Sciences, vol. 258, no. 1-2, pp. 69–74, 2007.
View at: Publisher Site | Google Scholar
S. Ouadghiri, K. El Alaoui Toussi, C. Brick et al., “Genetic factors and multiple sclerosis in the Moroccan population: A role for HLA class II,” Pathologie Biologie, vol. 61, no. 6, pp. 259–263, 2013.
View at: Publisher Site | Google Scholar
C. Ballerini, F. R. Guerini, G. Rombolà et al., “HLA-multiple sclerosis association in Continental Italy and correlation with disease prevalence in Europe,” Journal of Neuroimmunology, vol. 150, no. 1-2, pp. 178–185, 2004.
View at: Publisher Site | Google Scholar
A. N. Boiko, E. I. Gusev, M. A. Sudomoina et al., “Association and linkage of juvenile MS with HLA-DR2(15) in Russians,” Neurology, vol. 58, no. 4, pp. 658–660, 2002.
View at: Publisher Site | Google Scholar
V. P. Bozikas, M. C. Anagnostouli, P. Petrikis et al., “Familial bipolar disorder and multiple sclerosis: A three-generation HLA family study,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol. 27, no. 5, pp. 835–839, 2003.
View at: Publisher Site | Google Scholar
I. Kouri, S. Papakonstantinou, V. Bempes, H. S. Vasiliadis, A. P. Kyritsis, and S.-H. Pelidou, “HLA associations with multiple sclerosis in Greece,” Journal of the Neurological Sciences, vol. 308, no. 1-2, pp. 28–31, 2011.
View at: Publisher Site | Google Scholar
S. V. Ramagopalan, J. K. Byrnes, D. A. Dyment et al., “Parent-of-origin of HLA-DRB11501 and age of onset of multiple sclerosis,” Journal of Human Genetics, vol. 54, no. 9, pp. 547–549, 2009.
View at: Publisher Site | Google Scholar
S. V. Ramagopalan, N. J. Maugeri, L. Handunnetthi et al., “Expression of the multiple sclerosis-associated MHC class II allele HLA-DRB1*1501 is regulated by vitamin D,” PLoS Genetics, vol. 5, no. 2, 2009.
View at: Google Scholar
J. Wu, W. Qiu, A. Castley et al., “Modifying effects of HLA-DRB1 allele interactions on age at onset of multiple sclerosis in Western Australia,” Multiple Sclerosis Journal, vol. 16, no. 1, pp. 15–20, 2009.
View at: Publisher Site | Google Scholar
G. Disanto and S. V. Ramagopalan, “Similar genetics of adult and pediatric MS age is just a number,” Neurology, vol. 81, no. 23, pp. 1974-1975, 2013.
View at: Publisher Site | Google Scholar
J. S. Graves, L. F. Barcellos, S. Simpson et al., “The multiple sclerosis risk allele within the AHI1 gene is associated with relapses in children and adults,” Multiple Sclerosis and Related Disorders, vol. 19, pp. 161–165, 2018.
View at: Publisher Site | Google Scholar
M. A. Gianfrancesco, P. Stridh, X. Shao et al., “Genetic risk factors for pediatric-onset multiple sclerosis,” Multiple Sclerosis Journal, p. 135245851773355, 2017.
View at: Publisher Site | Google Scholar
P. H. Lalive, T. Menge, C. Delarasse et al., “Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 103, no. 7, pp. 2280–2285, 2006.
View at: Publisher Site | Google Scholar
P. Waters, M. Woodhall, K. C. O'Connor et al., “MOG cell-based assay detects non-MS patients with inflammatory neurologic disease,” Neurology - Neuroimmunology Neuroinflammation, vol. 2, no. 3, p. e89, 2015.
View at: Publisher Site | Google Scholar
K. Chalmoukou, H. Alexopoulos, S. Akrivou, P. Stathopoulos, M. Reindl, and M. C. Dalakas, “Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis,” Neurology - Neuroimmunology Neuroinflammation, vol. 2, no. 4, p. e131, 2015.
View at: Publisher Site | Google Scholar
R. S. Tsuburaya, N. Miki, K. Tanaka et al., “Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in a Japanese boy with recurrent optic neuritis,” Brain & Development, vol. 37, no. 1, pp. 145–148, 2015.
View at: Publisher Site | Google Scholar
A. Pröbstel, G. Rudolf, K. Dornmair et al., “Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype,” Journal of Neuroinflammation, vol. 12, no. 1, 2015.
View at: Publisher Site | Google Scholar
J. Hyun, M. R. Woodhall, S. Kim et al., “Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 88, no. 10, pp. 811–817, 2017.
View at: Publisher Site | Google Scholar
C. Linington, M. Bradl, H. Lassmann, C. Brunner, and K. Vass, “Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein,” The American Journal of Pathology, vol. 130, no. 3, pp. 443–454, 1988.
View at: Google Scholar
C. P. Genain, M.-H. Nguyen, N. L. Letvin et al., “Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate,” The Journal of Clinical Investigation, vol. 96, no. 6, pp. 2966–2974, 1995.
View at: Publisher Site | Google Scholar
M. J. Titulaer, R. Höftberger, T. Iizuka et al., “Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis,” Annals of Neurology, vol. 75, no. 3, pp. 411–428, 2014.
View at: Google Scholar
K. C. O'Connor, K. A. McLaughlin, P. L. De Jager et al., “Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein,” Nature Medicine, vol. 13, no. 2, pp. 211–217, 2007.
View at: Publisher Site | Google Scholar
K. A. McLaughlin, T. Chitnis, J. Newcombe et al., “Age-Dependent B Cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis,” The Journal of Immunology, vol. 183, no. 6, pp. 4067–4076, 2009.
View at: Publisher Site | Google Scholar
F. Brilot, R. C. Dale, R. C. Selter et al., “Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease,” Annals of Neurology, vol. 66, no. 6, pp. 833–842, 2009.
View at: Publisher Site | Google Scholar
K. Van Haren, B. H. Tomooka, B. A. Kidd et al., “Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing- Remitting multiple sclerosis,” Multiple Sclerosis Journal, vol. 19, no. 13, pp. 1726–1733, 2013.
View at: Publisher Site | Google Scholar
S. Kim, M. R. Woodhall, J. Kim et al., “Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS,” Neurology - Neuroimmunology Neuroinflammation, vol. 2, no. 6, p. e163, 2015.
View at: Publisher Site | Google Scholar
S. Mariotto, S. Ferrari, S. Monaco et al., “Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study,” Journal of Neurology, vol. 264, no. 12, pp. 2420–2430, 2017.
View at: Publisher Site | Google Scholar
Á. Cobo-Calvo, A. Ruiz, H. D’Indy et al., “MOG antibody-related disorders: common features and uncommon presentations,” Journal of Neurology, vol. 264, no. 9, pp. 1945–1955, 2017.
View at: Publisher Site | Google Scholar
S. Jarius, K. Ruprecht, I. Kleiter et al., “MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin,” Journal of Neuroinflammation, vol. 13, no. 1, 2016.
View at: Publisher Site | Google Scholar
S. Jarius, I. Kleiter, K. Ruprecht et al., “MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome,” Journal of Neuroinflammation, vol. 13, no. 1, 2016.
View at: Publisher Site | Google Scholar
F. Di Pauli, M. Reindl, and T. Berger, “New clinical implications of anti-myelin oligodendrocyte glycoprotein antibodies in children with CNS demyelinating diseases,” Multiple Sclerosis and Related Disorders, vol. 22, pp. 35–37, 2018.
View at: Publisher Site | Google Scholar
Y. Hacohen, K. Mankad, W. K. Chong et al., “Diagnostic algorithm for relapsing acquired demyelinating syndromes in children,” Neurology, vol. 89, no. 3, pp. 269–278, 2017.
View at: Publisher Site | Google Scholar
M. Juryńczyk, G. Tackley, Y. Kong et al., “Brain lesion distribution criteria distinguish MS from AQP4-antibody NMOSD and MOG-antibody disease,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 88, no. 2, pp. 132–136, 2017.
View at: Publisher Site | Google Scholar
C. Bensi, M. Marrodan, A. González et al., “Brain and spinal cord lesion criteria distinguishes AQP4-positive neuromyelitis optica and MOG-positive disease from multiple sclerosis,” Multiple Sclerosis and Related Disorders, vol. 25, pp. 246–250, 2018.
View at: Publisher Site | Google Scholar
S. Jarius, F. Paul, O. Aktas et al., “MOG encephalomyelitis: international recommendations on diagnosis and antibody testing,” Journal of Neuroinflammation, vol. 15, no. 1, 2018.
View at: Publisher Site | Google Scholar
A. S. López-Chiriboga, M. Majed, J. Fryer et al., “Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG–Associated Disorders,” JAMA Neurology, vol. 75, no. 11, p. 1355, 2018.
View at: Publisher Site | Google Scholar
T. G. Forsthuber, C. L. Shive, W. Wienhold et al., “T cell epitopes of human myelin oligodendrocyte glycoprotein identified in HLA-DR4 (DRB1*0401) transgenic mice are encephalitogenic and are presented by human B cells,” The Journal of Immunology, vol. 167, no. 12, pp. 7119–7125, 2001.
View at: Publisher Site | Google Scholar
J. Klehmet, C. Shive, R. Guardia-Wolff et al., “T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis,” Clinical Immunology, vol. 111, no. 1, pp. 53–60, 2004.
View at: Publisher Site | Google Scholar
M. Khare, M. Rodriguez, and C. S. David, “HLA class II transgenic mice authenticate restriction of myelin oligodendrocyte glycoprotein-specific immune response implicated in multiple sclerosis pathogenesis,” International Immunology, vol. 15, no. 4, pp. 535–546, 2003.
View at: Publisher Site | Google Scholar
K. Raddassi, S. C. Kent, J. Yang et al., “Increased frequencies of myelin oligodendrocyte glycoprotein/MHC class II-binding CD4 cells in patients with multiple sclerosis,” The Journal of Immunology, vol. 187, no. 2, pp. 1039–1046, 2011.
View at: Publisher Site | Google Scholar
A. Lutterotti, M. Reindl, C. Gassner et al., “Antibody response to myelin oligodendrocyte glycoprotein and myelin basic protein depend on familial background and are partially associated with human leukocyte antigen alleles in multiplex families and sporadic multiple sclerosis,” Journal of Neuroimmunology, vol. 131, no. 1-2, pp. 201–207, 2002.
View at: Publisher Site | Google Scholar
J. Sun, H. Link, T. Olsson et al., “T and B cell responses to myelinoligodendrocyte glycoprotein in multiple sclerosis,” The Journal of Immunology, vol. 146, no. 5, pp. 1490–1495, 1991.
View at: Google Scholar
D. Buck, S. Cepok, S. Hoffmann et al., “Influence of the HLA-DRB1 genotype on antibody development to interferon beta in multiple sclerosis,” JAMA Neurology, vol. 68, no. 4, pp. 480–487, 2011.
View at: Publisher Site | Google Scholar
E. Morandi, S. A. Jagessar, B. A. Hart, and B. Gran, “EBV infection empowers human b cells for autoimmunity: Role of autophagy and relevance to multiple sclerosis,” The Journal of Immunology, vol. 199, no. 2, pp. 435–448, 2017.
View at: Publisher Site | Google Scholar
H. H. Oh, S. H. Kwon, C. W. Kim et al., “Molecular analysis of HLA class II-associated susceptibility to neuroinflammatory diseases in Korean children,” Journal of Korean Medical Science, vol. 19, no. 3, pp. 426–430, 2004.
View at: Publisher Site | Google Scholar
M. Gontika and M. Anagnostouli, “Human leukocyte antigens-immunogenetics of neuromyelitis optica or Devic′s disease and the impact on the immunopathogenesis, diagnosis and treatment: a critical review,” Neuroimmunology and Neuroinflammation, vol. 1, no. 2, p. 44, 2014.
View at: Publisher Site | Google Scholar
D. Imbesi, R. S. Calabrò, G. Gervasi et al., “Does HLA Class II haplotype play a role in adult acute disseminated encephalomyelitis? Preliminary findings from a Southern Italy hospital-based study,” Archives Italiennes de Biologie, vol. 150, no. 1, pp. 1–4, 2012.
View at: Google Scholar
S. V. Alves-Leon, M. L. Veluttini-Pimentel, M. E. Gouveia et al., “Acute disseminated encephalomyelitis: Clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study,” Arquivos de Neuro-Psiquiatria, vol. 67, no. 3 A, pp. 643–651, 2009.
View at: Publisher Site | Google Scholar
Z. R. Idrissova, M. N. Boldyreva, E. P. Dekonenko et al., “Acute disseminated encephalomyelitis in children: clinical features and HLA-DR linkage,” European Journal of Neurology, vol. 10, no. 5, pp. 537–546, 2003.
View at: Publisher Site | Google Scholar
A. J. Thompson, B. L. Banwell, F. Barkhof et al., “Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria,” The Lancet Neurology, vol. 17, no. 2, pp. 162–173, 2018.
View at: Google Scholar
D. M. Wingerchuk, B. Banwell, J. L. Bennett et al., “International consensus diagnostic criteria for neuromyelitis optica spectrum disorders,” Neurology, vol. 85, no. 2, pp. 177–189, 2015.
View at: Publisher Site | Google Scholar
L. B. Krupp, M. Tardieu, M. P. Amato et al., “International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions,” Multiple Sclerosis Journal, vol. 19, no. 10, pp. 1261–1267, 2013.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2018 Maria P. Gontika and Maria C. Anagnostouli. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

2000

Downloads

1128

Citations