Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder

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Uzonyi , B , Szabo , Z , Trojnar , E , Hyvarinen , S , Uray , K , Nielsen , HH , Erdei , A , Jokiranta , TS , Prohaszka , Z , Illes , Z & Jozsi , M 2021 , ' Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder ' , Frontiers in Immunology , vol. 12 , 660382 . https://doi.org/10.3389/fimmu.2021.660382

Title: Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder
Author: Uzonyi, B; Szabo, Z; Trojnar, E; Hyvarinen, S; Uray, K; Nielsen, HH; Erdei, A; Jokiranta, TS; Prohaszka, Z; Illes, Z; Jozsi, M
Contributor organization: Immunobiology Research Program
Department of Bacteriology and Immunology
Clinicum
Research Programs Unit
Medicum
Doctoral Programme in Biomedicine
T. Sakari Jokiranta / Principal Investigator
Date: 2021-04-27
Language: eng
Number of pages: 13
Belongs to series: Frontiers in Immunology
ISSN: 1664-3224
DOI: https://doi.org/10.3389/fimmu.2021.660382
URI: http://hdl.handle.net/10138/337040
Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), characterized by pathogenic, complement-activating autoantibodies against the main water channel in the CNS, aquaporin 4 (AQP4). NMOSD is frequently associated with additional autoantibodies and antibody-mediated diseases. Because the alternative pathway amplifies complement activation, our aim was to evaluate the presence of autoantibodies against the alternative pathway C3 convertase, its components C3b and factor B, and the complement regulator factor H (FH) in NMOSD. Four out of 45 AQP4-seropositive NMOSD patients (similar to 9%) had FH autoantibodies in serum and none had antibodies to C3b, factor B and C3bBb. The FH autoantibody titers were low in three and high in one of the patients, and the avidity indexes were low. FH-IgG complexes were detected in the purified IgG fractions by Western blot. The autoantibodies bound to FH domains 19-20, and also recognized the homologous FH-related protein 1 (FHR-1), similar to FH autoantibodies associated with atypical hemolytic uremic syndrome (aHUS). However, in contrast to the majority of autoantibody-positive aHUS patients, these four NMOSD patients did not lack FHR-1. Analysis of autoantibody binding to FH19-20 mutants and linear synthetic peptides of the C-terminal FH and FHR-1 domains, as well as reduced FH, revealed differences in the exact binding sites of the autoantibodies. Importantly, all four autoantibodies inhibited C3b binding to FH. In conclusion, our results demonstrate that FH autoantibodies are not uncommon in NMOSD and suggest that generation of antibodies against complement regulating factors among other autoantibodies may contribute to the complement-mediated damage in NMOSD.
Subject: aquaporin (AQP) 4
complement
factor H
neuromyelitis optica spectrum disorder
autoantibody
autoimmunity
inflammation
central nervous system
MECHANISMS
PROTEIN-1
DISEASES
EPITOPES
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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