TY - JOUR
T1 - Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum
T2 - A Comparative Study
AU - Endmayr, Verena
AU - Tunc, Cansu
AU - Ergin, Lara
AU - De Rosa, Anna
AU - Weng, Rosa
AU - Wagner, Lukas
AU - Yu, Thin-Yau
AU - Fichtenbaum, Andreas
AU - Perkmann, Thomas
AU - Haslacher, Helmuth
AU - Kozakowski, Nicolas
AU - Schwaiger, Carmen
AU - Ricken, Gerda
AU - Hametner, Simon
AU - Klotz, Sigrid
AU - Dutra, Lívia Almeida
AU - Lechner, Christian
AU - de Simoni, Désirée
AU - Poppert, Kai-Nicolas
AU - Müller, Georg Johannes
AU - Pirker, Susanne
AU - Pirker, Walter
AU - Angelovski, Aleksandra
AU - Valach, Matus
AU - Maestri, Michelangelo
AU - Guida, Melania
AU - Ricciardi, Roberta
AU - Frommlet, Florian
AU - Sieghart, Daniela
AU - Pinter, Miklos
AU - Kircher, Karl
AU - Artacker, Gottfried
AU - Höftberger, Romana
AU - Koneczny, Inga
N1 - Publisher Copyright:
Copyright © 2022 Endmayr, Tunc, Ergin, De Rosa, Weng, Wagner, Yu, Fichtenbaum, Perkmann, Haslacher, Kozakowski, Schwaiger, Ricken, Hametner, Klotz, Dutra, Lechner, de Simoni, Poppert, Müller, Pirker, Pirker, Angelovski, Valach, Maestri, Guida, Ricciardi, Frommlet, Sieghart, Pinter, Kircher, Artacker, Höftberger and Koneczny.
PY - 2022/1/14
Y1 - 2022/1/14
N2 - Background: IgG4 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.Methods: We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD.Results: A 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.Conclusion: Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.
AB - Background: IgG4 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.Methods: We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD.Results: A 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.Conclusion: Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.
KW - Autoantibodies/immunology
KW - Autoantigens/immunology
KW - Female
KW - Humans
KW - Immunoglobulin G4-Related Disease/immunology
KW - Male
KW - Neurons/immunology
UR - https://www.scopus.com/pages/publications/85123759972
U2 - 10.3389/fimmu.2021.785247
DO - 10.3389/fimmu.2021.785247
M3 - Journal article
C2 - 35095860
VL - 12
SP - 785247
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 785247
ER -