A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission

Nóra Veszeli, György Füst, Dorottya Csuka, Anita Trauninger, Laszlo Bors, Csilla Rozsa, Zsuzsanna Nagy, Zita Jobbágy, Kornélia Eizler, Zoltán Prohászka, Lilian Varga, Zsolt Illes

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Abstract

Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS, but the three complement pathways have not been systematically investigated. We evaluated the overall activation of the classical, alternative, and MBL-lectin pathways in the peripheral blood of 25 patients with AQP4-seropositive NMO spectrum during remission and 113 healthy controls by three ways: (1) we measured the concentrations of native complement proteins of the three pathways [C1-inhibitor (C1-inh), C1q, C4, C3, C5, factor I, factor B, properdin]; (2) the concentrations of complement products suggesting in vivo activation (C1rC1sC1-inh, C3a, C3bBbP, and SC5b-9); and (3) the total activity of the three complement pathways. Additionally we measured levels of C1rC1sC1-inh, C3a, C3bBbP in cerebrospinal fluid (CSF) of 6 patients with relapsing NMO and of 18 patients with relapsing multiple sclerosis (MS). The serological studies indicated that total complement activity of the classical [median (interquartile range) 72 (61-82) vs. 65 (56-73) CH50/mL; p=0.0122] and of the lectin pathways [73 (59-111) vs. 49 (3-92)%; p=0.0078)] were elevated compared with the controls, whereas that of the alternative pathway was not significantly different. The levels of C3 [1.1 (0.9-1.3) vs. 1.4 (1.2-1.5)g/L; p
Original languageEnglish
JournalMolecular Immunology
Volume57
Issue number2
Pages (from-to)200-209
ISSN0161-5890
DOIs
Publication statusPublished - 2014

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Neuromyelitis Optica
Central Nervous System
Complement Factor B
Demyelinating Diseases
Cerebrospinal Fluid

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Veszeli, Nóra ; Füst, György ; Csuka, Dorottya ; Trauninger, Anita ; Bors, Laszlo ; Rozsa, Csilla ; Nagy, Zsuzsanna ; Jobbágy, Zita ; Eizler, Kornélia ; Prohászka, Zoltán ; Varga, Lilian ; Illes, Zsolt. / A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission. In: Molecular Immunology. 2014 ; Vol. 57, No. 2. pp. 200-209.
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title = "A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission",
abstract = "Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS, but the three complement pathways have not been systematically investigated. We evaluated the overall activation of the classical, alternative, and MBL-lectin pathways in the peripheral blood of 25 patients with AQP4-seropositive NMO spectrum during remission and 113 healthy controls by three ways: (1) we measured the concentrations of native complement proteins of the three pathways [C1-inhibitor (C1-inh), C1q, C4, C3, C5, factor I, factor B, properdin]; (2) the concentrations of complement products suggesting in vivo activation (C1rC1sC1-inh, C3a, C3bBbP, and SC5b-9); and (3) the total activity of the three complement pathways. Additionally we measured levels of C1rC1sC1-inh, C3a, C3bBbP in cerebrospinal fluid (CSF) of 6 patients with relapsing NMO and of 18 patients with relapsing multiple sclerosis (MS). The serological studies indicated that total complement activity of the classical [median (interquartile range) 72 (61-82) vs. 65 (56-73) CH50/mL; p=0.0122] and of the lectin pathways [73 (59-111) vs. 49 (3-92){\%}; p=0.0078)] were elevated compared with the controls, whereas that of the alternative pathway was not significantly different. The levels of C3 [1.1 (0.9-1.3) vs. 1.4 (1.2-1.5)g/L; p",
author = "N{\'o}ra Veszeli and Gy{\"o}rgy F{\"u}st and Dorottya Csuka and Anita Trauninger and Laszlo Bors and Csilla Rozsa and Zsuzsanna Nagy and Zita Jobb{\'a}gy and Korn{\'e}lia Eizler and Zolt{\'a}n Proh{\'a}szka and Lilian Varga and Zsolt Illes",
note = "Copyright {\circledC} 2013 Elsevier Ltd. All rights reserved.",
year = "2014",
doi = "10.1016/j.molimm.2013.09.010",
language = "English",
volume = "57",
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journal = "Molecular Immunology",
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Veszeli, N, Füst, G, Csuka, D, Trauninger, A, Bors, L, Rozsa, C, Nagy, Z, Jobbágy, Z, Eizler, K, Prohászka, Z, Varga, L & Illes, Z 2014, 'A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission', Molecular Immunology, vol. 57, no. 2, pp. 200-209. https://doi.org/10.1016/j.molimm.2013.09.010

A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission. / Veszeli, Nóra; Füst, György; Csuka, Dorottya; Trauninger, Anita; Bors, Laszlo; Rozsa, Csilla; Nagy, Zsuzsanna; Jobbágy, Zita; Eizler, Kornélia; Prohászka, Zoltán; Varga, Lilian; Illes, Zsolt.

In: Molecular Immunology, Vol. 57, No. 2, 2014, p. 200-209.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission

AU - Veszeli, Nóra

AU - Füst, György

AU - Csuka, Dorottya

AU - Trauninger, Anita

AU - Bors, Laszlo

AU - Rozsa, Csilla

AU - Nagy, Zsuzsanna

AU - Jobbágy, Zita

AU - Eizler, Kornélia

AU - Prohászka, Zoltán

AU - Varga, Lilian

AU - Illes, Zsolt

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2014

Y1 - 2014

N2 - Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS, but the three complement pathways have not been systematically investigated. We evaluated the overall activation of the classical, alternative, and MBL-lectin pathways in the peripheral blood of 25 patients with AQP4-seropositive NMO spectrum during remission and 113 healthy controls by three ways: (1) we measured the concentrations of native complement proteins of the three pathways [C1-inhibitor (C1-inh), C1q, C4, C3, C5, factor I, factor B, properdin]; (2) the concentrations of complement products suggesting in vivo activation (C1rC1sC1-inh, C3a, C3bBbP, and SC5b-9); and (3) the total activity of the three complement pathways. Additionally we measured levels of C1rC1sC1-inh, C3a, C3bBbP in cerebrospinal fluid (CSF) of 6 patients with relapsing NMO and of 18 patients with relapsing multiple sclerosis (MS). The serological studies indicated that total complement activity of the classical [median (interquartile range) 72 (61-82) vs. 65 (56-73) CH50/mL; p=0.0122] and of the lectin pathways [73 (59-111) vs. 49 (3-92)%; p=0.0078)] were elevated compared with the controls, whereas that of the alternative pathway was not significantly different. The levels of C3 [1.1 (0.9-1.3) vs. 1.4 (1.2-1.5)g/L; p

AB - Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS, but the three complement pathways have not been systematically investigated. We evaluated the overall activation of the classical, alternative, and MBL-lectin pathways in the peripheral blood of 25 patients with AQP4-seropositive NMO spectrum during remission and 113 healthy controls by three ways: (1) we measured the concentrations of native complement proteins of the three pathways [C1-inhibitor (C1-inh), C1q, C4, C3, C5, factor I, factor B, properdin]; (2) the concentrations of complement products suggesting in vivo activation (C1rC1sC1-inh, C3a, C3bBbP, and SC5b-9); and (3) the total activity of the three complement pathways. Additionally we measured levels of C1rC1sC1-inh, C3a, C3bBbP in cerebrospinal fluid (CSF) of 6 patients with relapsing NMO and of 18 patients with relapsing multiple sclerosis (MS). The serological studies indicated that total complement activity of the classical [median (interquartile range) 72 (61-82) vs. 65 (56-73) CH50/mL; p=0.0122] and of the lectin pathways [73 (59-111) vs. 49 (3-92)%; p=0.0078)] were elevated compared with the controls, whereas that of the alternative pathway was not significantly different. The levels of C3 [1.1 (0.9-1.3) vs. 1.4 (1.2-1.5)g/L; p

U2 - 10.1016/j.molimm.2013.09.010

DO - 10.1016/j.molimm.2013.09.010

M3 - Journal article

C2 - 24172223

VL - 57

SP - 200

EP - 209

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 2

ER -