Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis.
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.
Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck A-6020, Austria. patrick.peschl@i-med.ac.at.
Patrick
P
Peschl
Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck A-6020, Austria. ramberger.melanie@gmail.com.
Melanie
M
Ramberger
Institute of Neurology, Medical University of Vienna, Vienna A-1090, Austria. romana.hoeftberger@meduniwien.ac.at.
Romana
R
Höftberger
Tyrolean Cancer Research Institute, Innsbruck A-6020, Austria. karin.joehrer@tkfi.at.
Karin
K
Jöhrer
Division of Paediatric Neurology, Department of Paediatrics I, Medical University of Innsbruck, Innsbruck A-6020, Austria. matthias.baumann@tirol-kliniken.at.
Matthias
M
Baumann
Department of Paediatric Neurology, Witten/Herdecke University, Children's Hospital Datteln, Datteln D-45711, Germany. k.rostasy@kinderklinik-datteln.de.
Kevin
K
Rostásy
Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck A-6020, Austria. markus.reindl@i-med.ac.at.
Markus
M
Reindl
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers; D002648:Child; D016000:Cluster Analysis; D003429:Cross Reactions / Q000276:immunology; D004673:Encephalomyelitis, Acute Disseminated / Q000175:diagnosis* / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology; D040081:Protein Array Analysis; D011506:Proteins / Q000276:immunology; D020543:Proteome; D040901:Proteomics / Q000379:methods; D051381:Rats
D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C403049:CNTNAP2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D008565:Membrane Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D011506:Proteins; D020543:Proteome
acute disseminated encephalomyelitis; autoantibody; autoantigen; immunohistochemistry; paediatric; protein microarray