Matteo Gastaldi1,2, Silvia Scaranzin3, Sven Jarius4, Brigitte Wildeman4, Elisabetta Zardini3, Giulia Mallucci5, Eleonora Rigoni5, Elisa Vegezzi6, Thomas Foiadelli7, Salvatore Savasta7, Paola Banfi8, Maurizio Versino8, Luana Benedetti9, Giovanni Novi9,10, Margherita Maria Mancardi11, Thea Giacomini11, Pietro Annovazzi12, Damiano Baroncini12, Diana Ferraro13, Vito Lampasona14, Markus Reindl15, Patrick Waters16, Diego Franciotta3. 1. Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy. matteo.gastaldi@mondino.it. 2. Neuro-Oncology and Neuroinflammation Unit, IRCCS Mondino Foundation, Pavia, Italy. matteo.gastaldi@mondino.it. 3. Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy. 4. Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Otto Meyerhof Center, Heidelberg, Germany. 5. Multiple Sclerosis Centre, IRCCS Mondino Foundation, Pavia, Italy. 6. Neuro-Oncology and Neuroinflammation Unit, IRCCS Mondino Foundation, Pavia, Italy. 7. Pediatric Clinic, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. 8. Neurology and Stroke Unit, Circolo Hospital/Macchi Foundation, University of Insubria, Varese, Italy. 9. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy. 10. IRCCS Policlinico San Martino, Genoa, Italy. 11. Unit of Child Neuropsychiatry, Clinical and Surgical Neurosciences Department, IRCCS Istituto Giannina Gaslini, Genova, Italy. 12. Multiple Sclerosis Centre, ASST Valle Olona - Gallarate Hospital, Gallarate, Italy. 13. Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy. 14. San Raffaele Diabetes Research Institute, IRCCS San Raffaele Hospital, Milan, Italy. 15. Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. 16. Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK.
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-IgGH+L), and a live-CBA for IgG1 (LCBA-IgG1). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fcγ secondary-antibody (LCBA-IgGFcγ), and a commercial fixed-CBA with anti-Fcγ secondary-antibody (FCBA-IgGFcγ). 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-IgGH+L, and 74.6% (CI:61.0-85.3) and 100% (CI:97.6-100) for LCBA-IgG1. Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG1); of these, three with 'possible MOGAD' showed high-titer MOG-IgG (≥ 1:640), and positivity for MOG-IgG2, 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-IgGFcγ, and 87.2% (CI:72.6-95.7) and 97.0% (CI:83.8-99.9) for FCBA-IgGFcγ. CONCLUSIONS: LCBA-IgG1 showed the highest specificity but can miss MOG-IgG2 reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgGH+L/ IgGFcγ is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgGFcγ yielded the highest accuracy, and FCBA-IgGFcγ good specificity, but it was at risk of false-negative results.
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-IgGH+L), and a live-CBA for IgG1 (LCBA-IgG1). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fcγ secondary-antibody (LCBA-IgGFcγ), and a commercial fixed-CBA with anti-Fcγ secondary-antibody (FCBA-IgGFcγ). 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-IgGH+L, and 74.6% (CI:61.0-85.3) and 100% (CI:97.6-100) for LCBA-IgG1. Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG1); of these, three with 'possible MOGAD' showed high-titer MOG-IgG (≥ 1:640), and positivity for MOG-IgG2, 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-IgGFcγ, and 87.2% (CI:72.6-95.7) and 97.0% (CI:83.8-99.9) for FCBA-IgGFcγ. CONCLUSIONS:LCBA-IgG1 showed the highest specificity but can miss MOG-IgG2 reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgGH+L/ IgGFcγ is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgGFcγ yielded the highest accuracy, and FCBA-IgGFcγ good specificity, but it was at risk of false-negative results.
Authors: Gianvito Masi; Yingkai Li; Tabitha Karatz; Minh C Pham; Seneca R Oxendine; Richard J Nowak; Jeffrey T Guptill; Kevin C O'Connor Journal: J Neuroimmunol Date: 2022-03-25 Impact factor: 3.221
Authors: Luciana G Lazaro; Jhon E Perea Cossio; Maria B Luis; Flavia Tamagnini; Diego A Paguay Mejia; Horacio Solarz; Nora A Fernandez Liguori; Ricardo N Alonso Journal: Brain Behav Immun Health Date: 2022-03-01
Authors: Kathrin Schanda; Patrick Peschl; Magdalena Lerch; Barbara Seebacher; Swantje Mindorf; Nora Ritter; Monika Probst; Harald Hegen; Franziska Di Pauli; Eva-Maria Wendel; Christian Lechner; Matthias Baumann; Sara Mariotto; Sergio Ferrari; Albert Saiz; Michael Farrell; Maria Isabel S Leite; Sarosh R Irani; Jacqueline Palace; Andreas Lutterotti; Tania Kümpfel; Sandra Vukusic; Romain Marignier; Patrick Waters; Kevin Rostasy; Thomas Berger; Christian Probst; Romana Höftberger; Markus Reindl Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-06-15