Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis

Pröbstel, Anne-Katrin; Dornmair, Klaus; Bittner, Robert A.; Sperl, P; Jenne, Dieter E.; Magalhaes, Sandra; Villalobos, Alvarez; Breithaupt, Constanze; Weissert, Robert; Jacob, Uwe; Krumbholz, Markus; Kuempfel, Tania; Blaschek, Astrid; Stark, Wiebke; Gärtner, Jutta; Pohl, Daniela; Rostásy, Kevin; Weber, Felix; Forné, Ignasi; Khademi, Mohsen; Olsson, Tomas; Brilot, Fabienne; Tantsis, Esther; Dale, Russell C.; Wekerle, Hartmut; Hohlfeld, Reinhard; Banwell, Brenda; Bar‐Or, Amit; Meinl, Edgar; Derfuss, Tobias

doi:10.1212/wnl.0b013e318228c0b1

Cited by 284 publications

(279 citation statements)

References 29 publications

Supporting

Mentioning

270

Contrasting

Unclassified

Order By: Relevance

“…Anti-MOG antibodies were measured in sera and in culture supernatants by flow cytometry as previously described (3). Supernatants were mixed with two volumes of reporter cell suspension in PBS containing 2% FCS by volume and 1 g/L of sodium azide on ice.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cocapture of cognate and bystander antigens can activate autoreactive B cells

Sanderson

Zimmermann

Eilinger

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with autoimmune central nervous system diseases like acute disseminated encephalomyelitis (ADEM). For ADEM, it is speculated that a preceding infection is the trigger of the autoimmune response, but the mechanism connecting the infection to the production of MOG antibodies remains a mystery. We reasoned that the ability of B cells to capture cognate antigen from cell membranes, along with small quantities of coexpressed "bystander" antigens, might enable B-cell escape from tolerance. We tested this hypothesis using influenza hemagglutinin as a model viral antigen and transgenic, MOG-specific B cells. Using flow cytometry and live and fixed cell microscopy, we show that MOG-specific B cells take up large amounts of MOG from cell membranes. Uptake of the antigen from the membrane leads to a strong activation of the capturing B cell. When influenza hemagglutinin is also present in the membrane of the target cell, it can be cocaptured with MOG by MOG-specific B cells via the B-cell receptor. Hemagglutinin and MOG are both presented to T cells, which in turn are activated and proliferate. As a consequence, MOG-specific B cells get help from hemagglutinin-specific T cells to produce anti-MOG antibodies. In vivo, the transfer of MOG-specific B cells into recipient mice after the cocapture of MOG and hemagglutinin leads to the production of class-switched anti-MOG antibodies, dependent on the presence of hemagglutinin-specific T cells. This mechanism offers a link between infection and autoimmunity.tolerance | autoantibodies | antigen capture | antigen presentation | influenza

show abstract

Section: Methodsmentioning

confidence: 99%

“…Among the most important suspected viral triggers of ADEM is influenza virus infection (2). It is also known that pediatric patients with ADEM especially mount a humoral immune response against myelin oligodendrocyte glycoprotein (MOG) (3). The mechnism through which the viral infection leads to the production of autoantibodies is unknown.…”

mentioning

confidence: 99%

Cocapture of cognate and bystander antigens can activate autoreactive B cells

Sanderson

Zimmermann

Eilinger

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…[14][15][16][17][18] In contrast, the clinical relevance of MOG antibodies in adults is unclear, as only a minority of patients with MS and NMO/NMOSD are seropositive. 16,[18][19][20][21][22][23][24] Herein, we provide evidence that MOG antibodies are a clinical biomarker of bilateral and/ or recurrent optic neuritis (BON) in adults and describe the characteristic clinical course, response to therapy, and visual outcomes of this condition.…”

mentioning

confidence: 99%

“…11 In particular, flow cytometry has emerged as a sensitive detection method, 6,14,16,21,32 with recent confirmation of the surface expression of the dominant MOG epitopes. 33 We describe that surface MOG IgG antibodies have a strong association with BON in adults.…”

mentioning

confidence: 99%

Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis

Ramanathan

Reddel

Henderson

et al. 2014

Journal of Neuroimmunology

110

View full text Add to dashboard Cite

“…A high proportion of patients with ADEM, especially children, are found to have antibodies directed toward myelin oligodendrocytes glycoprotein [63][64][65][66]. AHLE has been reported to occur in the context of several different viral infections, including cytomegalovirus, Epstein Barr virus, herpes simplex virus, the mumps virus, and the H1N1 virus [67][68][69][70][71].…”

Section: Ademmentioning

confidence: 99%

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

Geldern¹,

McPharlin

Becker

2012

Neurotherapeutics

View full text Add to dashboard Cite

This chapter will review the spectrum of immunemediated diseases that affect the nervous system and may result in an admission to the neurological intensive care unit. Immunomodulatory strategies to treat acute exacerbations of neurological diseases caused by aberrant immune responses are discussed, but strategies for long-term immunosuppression are not presented. The recommendations for therapeutic intervention are based on a synthesis of the literature, and include recommendations by the Cochrane Collaborative, the American Academy of Neurology, and other key organizations. References from recent publications are provided for the disorders and therapies in which randomized clinical trials and large evidenced-based reviews do not exist. The chapter concludes with a brief review of the mechanisms of action, dosing, and side effects of commonly used immunosuppressive strategies in the neurocritical care unit.

show abstract

Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis

Abstract: The persistence or disappearance of antibodies to MOG may have prognostic relevance for acute childhood demyelination.

Cited by 284 publications

References 29 publications

Cocapture of cognate and bystander antigens can activate autoreactive B cells

Cocapture of cognate and bystander antigens can activate autoreactive B cells

Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

Contact Info

Product

Resources

About