Katalin T Kovacs1, Sudhakar Reddy Kalluri2, Antonio Boza-Serrano3, Tomas Deierborg3, Tunde Csepany4, Magdolna Simo5, Laszlo Rokusz6, Attila Miseta7, Nicolas Alcaraz8, Laszlo Czirjak1, Timea Berki9, Tihamer Molnar10, Bernhard Hemmer11, Zsolt Illes12. 1. Department of Rheumatology and Immunology, University of Pecs, Hungary. 2. Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany. 3. Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, Lund University, Sweden. 4. Department of Neurology, University of Debrecen, Hungary. 5. Department of Neurology, Semmelweis University, Hungary. 6. 1st Department of Internal Medicine, Military Hospital - State Health Centre, Hungary. 7. Department of Laboratory Medicine, University of Pecs, Hungary. 8. Computational Biology Group, Department of Mathematics and Computer Science (IMADA), University of Southern Denmark, Denmark. 9. Department of Immunology and Biotechnology, University of Pecs, Hungary. 10. Department of Anesthesiology and Intensive Care, University of Pecs, Hungary. 11. Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany/Munich Cluster for Systems Neurology (SyNergy), Germany. 12. Department of Neurology, Odense University Hospital, Denmark/Institute of Clinical Research, University of Southern Denmark, Denmark zsolt.illes@rsyd.dk.
Abstract
BACKGROUND: Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. OBJECTIVE: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute. METHODS: In 19 samples of six patients who developed NMO during SLE, we examined the correlation of AQP4-IgG1 and IgM with (i) anti-MOG IgG and IgM, (ii) anti-nuclear, anti-nucleosome and anti-dsDNA IgG antibodies, (iii) cytokines and chemokines in the serum and (iv) longitudinal relation to NMO relapses/remission. RESULTS: AQP4-IgG1 was present 1-2-5 years before the first NMO relapse. During relapse, AQP4-IgG1, ANA, anti-dsDNA and anti-nucleosome antibodies were elevated. Anti-MOG IgG/IgM and AQP4-IgM antibodies were not detected. AQP4-IgG1 antibodies correlated with concentration of anti-nucleosome, IFN-γ,interferon-gamma-induced CCL10/IP-10 and CCL17/TARC (p<0.05, respectively). CCL17/TARC correlated with levels of anti-nucleosome and anti-dsDNA (p<0.05, respectively). Compared to healthy subjects, concentration of IFN-γ and CCL17/TARC was higher in NMO/SLE (p<0.05). CONCLUSIONS: AQP4-IgG1 antibodies are present in the sera years before the first NMO attack in patients with SLE; elevation of anti-AQP4 is part of a polyclonal B cell response during NMO relapses; in spite of multiple autoantibodies in the serum, MOG antibodies were not present; Th1 responses accompany autoantibody responses in NMO/SLE.
BACKGROUND:Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. OBJECTIVE: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute. METHODS: In 19 samples of six patients who developed NMO during SLE, we examined the correlation of AQP4-IgG1 and IgM with (i) anti-MOG IgG and IgM, (ii) anti-nuclear, anti-nucleosome and anti-dsDNA IgG antibodies, (iii) cytokines and chemokines in the serum and (iv) longitudinal relation to NMO relapses/remission. RESULTS:AQP4-IgG1 was present 1-2-5 years before the first NMO relapse. During relapse, AQP4-IgG1, ANA, anti-dsDNA and anti-nucleosome antibodies were elevated. Anti-MOG IgG/IgM and AQP4-IgM antibodies were not detected. AQP4-IgG1 antibodies correlated with concentration of anti-nucleosome, IFN-γ,interferon-gamma-induced CCL10/IP-10 and CCL17/TARC (p<0.05, respectively). CCL17/TARC correlated with levels of anti-nucleosome and anti-dsDNA (p<0.05, respectively). Compared to healthy subjects, concentration of IFN-γ and CCL17/TARC was higher in NMO/SLE (p<0.05). CONCLUSIONS:AQP4-IgG1 antibodies are present in the sera years before the first NMO attack in patients with SLE; elevation of anti-AQP4 is part of a polyclonal B cell response during NMO relapses; in spite of multiple autoantibodies in the serum, MOG antibodies were not present; Th1 responses accompany autoantibody responses in NMO/SLE.
Authors: Barbara Uzonyi; Zsóka Szabó; Eszter Trojnár; Satu Hyvärinen; Katalin Uray; Helle H Nielsen; Anna Erdei; T Sakari Jokiranta; Zoltán Prohászka; Zsolt Illes; Mihály Józsi Journal: Front Immunol Date: 2021-04-27 Impact factor: 7.561
Authors: Nellie A Martin; Arkadiusz Nawrocki; Viktor Molnar; Maria L Elkjaer; Eva K Thygesen; Miklos Palkovits; Peter Acs; Tobias Sejbaek; Helle H Nielsen; Zoltan Hegedus; Finn Sellebjerg; Tihamer Molnar; Eudes G V Barbosa; Nicolas Alcaraz; Ferenc Gallyas; Asa F Svenningsen; Jan Baumbach; Hans Lassmann; Martin R Larsen; Zsolt Illes Journal: PLoS One Date: 2018-08-16 Impact factor: 3.240