Abstract
Human antibodies against Myelin Oligodendrocyte Glycoprotein (MOG) from immunoglobulin-G subclasses (MOG-IgG) have been recently associated with a new subgroup of neurological autoimmune diseases with distinct clinical characteristics from multiple sclerosis and neuromyelitis optica spectrum disorders. The use of MOG-IgG as a biomarker is an essential tool to assist in the diagnosis and clinical prognosis. The cell-based assay (CBA) is a methodology that expresses high levels of natively folded human MOG protein in the cell membrane being the methodology most used for clinical MOG-IgG diagnosis. However, there is still no consensus about the best approach to perform CBA to improve the results. The CBA using flow cytometry (CBA-FC) is an automated technique with objective quantification, reducing the subject of human bias that occurred at CBA using immunofluorescence (CBA-IF). In this study, we compared the performance of CBA-IF and CBA-FC as an acquisition tool analysis. The sera of 104 patients diagnosed with inflammatory Central Nervous System diseases were tested in both CBA-IF and CBA-FC. We used the dilution of 1:128 for CBA-IF and three different dilutions (1:20, 1:100, and 1:640) for CBA-FC. The CBA-FC and CBA-IF results had 88.5% agreement between assays and the CBA-IF titers by endpoint-dilution correlated with the CBA-FC titers. The highest serum dilution resulted in an increased CBA-FC specificity, but there was a reduction in the CBA-FC sensitivity. Our study showed that CBA-FC can be used in clinical practice as a diagnostic technique for MOG-IgG. In addition, in some specific cases, the combination of both techniques could be used as a tool to discriminate unspecific binding and overcome single assay limitations.
Highlights
Myelin Oligodendrocyte Glycoprotein (MOG) is a protein exclusively expressed in the Central Nervous System (CNS)
The MOG from immunoglobulin-G subclasses (MOG-IgG)- group had a clinical diagnosis as follows: 25.9% had Optic Neuritis (ON), 27.6% had myelitis, 3.5% were clinically diagnosed with seronegative neuromyelitis optica spectrum disorders (NMOSD), 5.2% were diagnosed with AQP4-NMOSD
The MOG-associated disorder (MOGAD) or MONEM is a new subgroup of neurological autoimmune disorders, distinct from multiple sclerosis (MS) and aquaporin-4-IgG+
Summary
Myelin Oligodendrocyte Glycoprotein (MOG) is a protein exclusively expressed in the Central Nervous System (CNS). The human antibodies against MOG from immunoglobulin-G subclasses (MOG-IgG) have been recently associated with a new subgroup of neurological autoimmune diseases, with distinct clinical characteristics and prognosis from multiple sclerosis (MS) and aquaporin-4-IgG positive neuromyelitis optica spectrum disorders (NMOSD). Our group proposed the acronym MONEM to facilitate the identification of suspected cases as most the MOG-IgG+ patients present with attacks of Optic Neuritis (ON), Encephalitis, and/or Myelitis [3], but some other groups have used the term MOG-associated disorder (MOGAD) [4]. The presence of MOG-IgG occurs in some patients that can be clinically diagnosed with aquaporin-4-IgG seronegative NMOSD, acute disseminated encephalomyelitis (ADEM), and cortical encephalitis [8,9,10]. The MONEM cases are found in Caucasian and non-Caucasian paediatric and adult patients with a slight female predominance [6, 11, 12]
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