Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis.

Patrick Peschl,Romana Höftberger,Markus Reindl,Karin Jöhrer,Melanie Ramberger,Matthias Baumann,Kevin Rostásy

doi:10.3390/ijms18030679

Abstract

Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients. Therefore, we aimed to identify novel autoantibody targets in ADEM patients. Sixteen ADEM patients (11 seronegative, 5 seropositive for MOG antibodies) were analysed for potential new biomarkers, using a protein microarray and immunohistochemistry on rat brain tissue to identify antibodies against intracellular and surface neuronal and glial antigens. Nine candidate antigens were identified in the protein microarray analysis in at least two patients per group. Immunohistochemistry on rat brain tissue did not reveal new target antigens. Although no new autoantibody targets could be found here, future studies should aim to identify new biomarkers for therapeutic and prognostic purposes. The microarray analysis and immunohistochemistry methods used here have several limitations, which should be considered in future searches for biomarkers.

Highlights

Acute disseminated encephalomyelitis (ADEM) is an autoimmune disorder of the central nervous system (CNS) mainly affecting children and young adults
One potential biomarker is an autoantibody against myelin oligodendrocyte glycoprotein (MOG), which is located on the outermost surface of myelin sheaths and oligodendrocytes
Baumann and colleagues found that 58% of investigated ADEM patients were positive for MOG antibodies at disease onset, with a significantly better recovery compared to seronegative patients [12]

Summary

Introduction

Acute disseminated encephalomyelitis (ADEM) is an autoimmune disorder of the central nervous system (CNS) mainly affecting children and young adults. The disease course is mainly monophasic with partial or complete recovery, and multiphasic forms of ADEM have been observed with a recurrence of the initial symptoms or more distinct ADEM episodes appearing at least three months after the first event, making the differentiation to multiple sclerosis (MS) not always simple [2]. Baumann and colleagues found that 58% of investigated ADEM patients were positive for MOG antibodies at disease onset, with a significantly better recovery compared to seronegative patients [12]. A considerable group of ADEM patients are seronegative for MOG antibodies, usually responding to anti-inflammatory treatment regimens or plasmapheresis, indicating the role of other yet unknown autoantibodies in the pathogenesis of the disease

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Conclusion