Improving the sensitivity of myelin oligodendrocyte glycoprotein-antibody testing: exclusive or predominant MOG-IgG3 seropositivity-a potential diagnostic pitfall in patients with MOG-EM/MOGAD.

التفاصيل البيبلوغرافية
العنوان:	Improving the sensitivity of myelin oligodendrocyte glycoprotein-antibody testing: exclusive or predominant MOG-IgG3 seropositivity-a potential diagnostic pitfall in patients with MOG-EM/MOGAD.
المؤلفون:	Jarius S; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de., Ringelstein M; Department of Neurology, Heinrich Heine University, Düsseldorf, Germany., Schanda K; Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria., Ruprecht K; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Korporal-Kuhnke M; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany., Viehöver A; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany., Hümmert MW; Department of Neurology, Hannover Medical School, Hanover, Germany., Schindler P; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Endmayr V; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria., Gastaldi M; Neuroimmunology Laboratory and Neuroimmunology Research Unit, IRCCS Mondino Foundation National Neurological Institute, Pavia, Italy., Trebst C; Department of Neurology, Hannover Medical School, Hanover, Germany., Franciotta D; Neuroimmunology Laboratory and Neuroimmunology Research Unit, IRCCS Mondino Foundation National Neurological Institute, Pavia, Italy., Aktas O; Department of Neurology, Heinrich Heine University, Düsseldorf, Germany., Höftberger R; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria., Haas J; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany., Komorowski L; Institute of Experimental Neuroimmunology, affiliated to Euroimmun AG, Lübeck, Germany., Paul F; Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany.; Neuroscience Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Reindl M; Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria., Wildemann B; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. brigitte.wildemann@med.uni-heidelberg.de.
المصدر:	Journal of neurology [J Neurol] 2024 Jul; Vol. 271 (7), pp. 4660-4671. Date of Electronic Publication: 2024 Apr 13.
نوع المنشور:	Journal Article; Letter
اللغة:	English
بيانات الدورية:	Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0423161 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1459 (Electronic) Linking ISSN: 03405354 NLM ISO Abbreviation: J Neurol Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Berlin ; New York, Springer-Verlag
مواضيع طبية MeSH:	Myelin-Oligodendrocyte Glycoprotein/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Autoantibodies/blood, Humans ; Female ; Male ; Adult ; Middle Aged ; Sensitivity and Specificity ; Young Adult ; Aged ; Encephalomyelitis/diagnosis ; Encephalomyelitis/immunology ; Encephalomyelitis/blood
مستخلص:	Background: Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated. Objective: To assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing. Methods: Re-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion). Results: In accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 [93%] samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 [55%] patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 [32%] patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA ⁺ /IgG ^- MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested. Conclusions: In some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and-just like H+L- and Fcγ-specific testing-might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted. (© 2024. The Author(s).)
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فهرسة مساهمة:	Keywords: Antibodies; Aquaporin-4 (AQP4); Assays; Autoantibody; Detection antibodies; IgG subclasses; Immunoglobulin G (IgG); MOG antibody-associated disease (MOGAD); MOG antibody-associated encephalomyelitis (MOG-EM); MOG-IgG1; MOG-IgG3; Multiple sclerosis; Myelin oligodendrocyte glycoprotein (MOG); Myelitis; Neuromyelitis optica spectrum disorders (NMOSD); Optic neuritis; Rozanolixizumab; Sensitivity; Seroconversion; Serology; Seronegative; Seronegativity; Seroreversion; Tests
المشرفين على المادة:	0 (Myelin-Oligodendrocyte Glycoprotein) 0 (Immunoglobulin G) 0 (Autoantibodies) 0 (MOG protein, human)
تواريخ الأحداث:	Date Created: 20240412 Date Completed: 20240709 Latest Revision: 20240731
رمز التحديث:	20240801
مُعرف محوري في PubMed:	PMC11233316
DOI:	10.1007/s00415-024-12285-5
PMID:	38609667
قاعدة البيانات:	MEDLINE

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