Frontiers in Immunology (Jan 2022)
Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study
- Verena Endmayr,
- Cansu Tunc,
- Lara Ergin,
- Anna De Rosa,
- Rosa Weng,
- Lukas Wagner,
- Thin-Yau Yu,
- Andreas Fichtenbaum,
- Thomas Perkmann,
- Helmuth Haslacher,
- Nicolas Kozakowski,
- Carmen Schwaiger,
- Gerda Ricken,
- Simon Hametner,
- Sigrid Klotz,
- Lívia Almeida Dutra,
- Christian Lechner,
- Christian Lechner,
- Désirée de Simoni,
- Désirée de Simoni,
- Kai-Nicolas Poppert,
- Georg Johannes Müller,
- Susanne Pirker,
- Walter Pirker,
- Aleksandra Angelovski,
- Matus Valach,
- Michelangelo Maestri,
- Melania Guida,
- Roberta Ricciardi,
- Florian Frommlet,
- Daniela Sieghart,
- Miklos Pinter,
- Karl Kircher,
- Gottfried Artacker,
- Romana Höftberger,
- Inga Koneczny
Affiliations
- Verena Endmayr
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Cansu Tunc
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Lara Ergin
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Anna De Rosa
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
- Rosa Weng
- Department of Neurology, Medical University of Vienna, Vienna, Austria
- Lukas Wagner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Thin-Yau Yu
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Andreas Fichtenbaum
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
- Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
- Helmuth Haslacher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
- Nicolas Kozakowski
- Department of Pathology, Medical University of Vienna, Vienna, Austria
- Carmen Schwaiger
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Gerda Ricken
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Simon Hametner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Sigrid Klotz
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Lívia Almeida Dutra
- Department of Neurology and Neurosurgery, Hospital Israelita Albert Einstein, São Paulo, Brazil
- Christian Lechner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Christian Lechner
- Pediatric Neurology, Department of Pediatric and Adolescent Medicine, Medical University of Innsbruck, Innsbruck, Austria
- Désirée de Simoni
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Désirée de Simoni
- Department of Neurology, University Hospital St. Poelten, St. Poelten, Austria
- Kai-Nicolas Poppert
- Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
- Georg Johannes Müller
- 0Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria
- Susanne Pirker
- 1Department of Neurology, Klinik Hietzing, Vienna, Austria
- Walter Pirker
- 2Department of Neurology, Klinik Ottakring, Vienna, Austria
- Aleksandra Angelovski
- 2Department of Neurology, Klinik Ottakring, Vienna, Austria
- Matus Valach
- 3Department of Pathology, Klinik Landstrasse, Vienna, Austria
- Michelangelo Maestri
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
- Melania Guida
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
- Roberta Ricciardi
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
- Florian Frommlet
- 4Center for Medical Statistics, Informatics and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Vienna, Austria
- Daniela Sieghart
- 5Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Miklos Pinter
- 6Wiener Privatklinik – Health Center, Vienna, Austria
- Karl Kircher
- 7Department of Ophthalmology, Medical University of Vienna, Vienna, Austria
- Gottfried Artacker
- 8Department of Pediatrics and Adolescent Medicine, Klinik Donaustadt, Vienna, Austria
- Romana Höftberger
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Inga Koneczny
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- DOI
- https://doi.org/10.3389/fimmu.2021.785247
- Journal volume & issue
-
Vol. 12
Abstract
BackgroundIgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features.MethodsWe collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD.ResultsA significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD.ConclusionOur observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.
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