Background The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the differential diagnosis of acquired demyelinating syndromes of the CNS, among which multiple sclerosis (MS). We compared the diagnostic performance of four cell-based assays (CBAs) for their detection. Methods Consecutive sera from 204 patients with 'possible MOGAD' (55), MS (112), and other neurological disorders (OND, 37) were tested for MOG-IgG with a live-CBA with anti-heavy-and-light chain secondary-antibody (LCBA-IgG(H+L)), and a live-CBA for IgG(1)(LCBA-IgG(1)). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fc gamma secondary-antibody (LCBA-IgG(Fc gamma)), and a commercial fixed-CBA with anti-Fc gamma secondary-antibody (FCBA-IgG(Fc gamma))(.) Results Fifty-seven/204 patients (27.9%) were MOG-IgG-positive. Sensitivity was 89.1% (CI:77.8-95.9) and specificity 93.3% (CI:88.0-96.7) for LCBA-IgG(H+L), and 74.6% (CI:61.0-85.3) and 100% (CI:97.6-100) for LCBA-IgG(1). Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG(1)); of these, three with 'possible MOGAD' showed high-titer MOG-IgG (>= 1:640), and positivity for MOG-IgG(2), whereas 15/18 had low-titer MOG-IgG (1:160/1:320) and mixed diagnoses (5 'possible MOGAD', 6 MS, 4 OND). In the subgroup analysis, sensitivity was 92.3% (CI:79.1-98.4) and specificity 97.0% (CI:83.8-99.9) for LCBA-IgG(Fc gamma), and 87.2% (CI:72.6-95.7) and 97.0% (CI:83.8-99.9) for FCBA-IgG(Fc gamma). Conclusions LCBA-IgG(1)showed the highest specificity but can miss MOG-IgG(2)reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgG(H+L)/ IgG(Fc gamma)is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgG(Fc gamma)yielded the highest accuracy, and FCBA-IgG(Fc gamma)good specificity, but it was at risk of false-negative results.

Cell-based assays for the detection of MOG antibodies: a comparative study

Savasta S
Investigation
;
2020

Abstract

Background The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the differential diagnosis of acquired demyelinating syndromes of the CNS, among which multiple sclerosis (MS). We compared the diagnostic performance of four cell-based assays (CBAs) for their detection. Methods Consecutive sera from 204 patients with 'possible MOGAD' (55), MS (112), and other neurological disorders (OND, 37) were tested for MOG-IgG with a live-CBA with anti-heavy-and-light chain secondary-antibody (LCBA-IgG(H+L)), and a live-CBA for IgG(1)(LCBA-IgG(1)). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fc gamma secondary-antibody (LCBA-IgG(Fc gamma)), and a commercial fixed-CBA with anti-Fc gamma secondary-antibody (FCBA-IgG(Fc gamma))(.) Results Fifty-seven/204 patients (27.9%) were MOG-IgG-positive. Sensitivity was 89.1% (CI:77.8-95.9) and specificity 93.3% (CI:88.0-96.7) for LCBA-IgG(H+L), and 74.6% (CI:61.0-85.3) and 100% (CI:97.6-100) for LCBA-IgG(1). Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG(1)); of these, three with 'possible MOGAD' showed high-titer MOG-IgG (>= 1:640), and positivity for MOG-IgG(2), whereas 15/18 had low-titer MOG-IgG (1:160/1:320) and mixed diagnoses (5 'possible MOGAD', 6 MS, 4 OND). In the subgroup analysis, sensitivity was 92.3% (CI:79.1-98.4) and specificity 97.0% (CI:83.8-99.9) for LCBA-IgG(Fc gamma), and 87.2% (CI:72.6-95.7) and 97.0% (CI:83.8-99.9) for FCBA-IgG(Fc gamma). Conclusions LCBA-IgG(1)showed the highest specificity but can miss MOG-IgG(2)reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgG(H+L)/ IgG(Fc gamma)is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgG(Fc gamma)yielded the highest accuracy, and FCBA-IgG(Fc gamma)good specificity, but it was at risk of false-negative results.
Myelin oligodendrocyte glycoprotein; Autoantibodies; Cell-based assay; Demyelinating disorders; Standardization; Myelitis; Optic neuritis; Multiple sclerosis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/344605
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