Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus

BackgroundTo date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We aimed to assess the function of these three C cascades through functional assays and the m...

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Main Authors: María García-González, Fuensanta Gómez-Bernal, Juan C. Quevedo-Abeledo, Yolanda Fernández-Cladera, Agustín F. González-Rivero, Antonia de Vera-González, Iñigo de la Rua-Figueroa, Raquel López-Mejias, Federico Díaz-González, Miguel Á. González-Gay, Iván Ferraz-Amaro
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1167055/full
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author María García-González
Fuensanta Gómez-Bernal
Juan C. Quevedo-Abeledo
Yolanda Fernández-Cladera
Agustín F. González-Rivero
Antonia de Vera-González
Iñigo de la Rua-Figueroa
Raquel López-Mejias
Federico Díaz-González
Federico Díaz-González
Miguel Á. González-Gay
Miguel Á. González-Gay
Miguel Á. González-Gay
Iván Ferraz-Amaro
Iván Ferraz-Amaro
author_facet María García-González
Fuensanta Gómez-Bernal
Juan C. Quevedo-Abeledo
Yolanda Fernández-Cladera
Agustín F. González-Rivero
Antonia de Vera-González
Iñigo de la Rua-Figueroa
Raquel López-Mejias
Federico Díaz-González
Federico Díaz-González
Miguel Á. González-Gay
Miguel Á. González-Gay
Miguel Á. González-Gay
Iván Ferraz-Amaro
Iván Ferraz-Amaro
author_sort María García-González
collection DOAJ
description BackgroundTo date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics.MethodsNew generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system.ResultsLower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-β2GP, predominantly involving the AL pathway.ConclusionNot only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.
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spelling doaj.art-691ccd8bd5b24f8cbc4197522fd2aa6e2023-04-21T04:30:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11670551167055Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosusMaría García-González0Fuensanta Gómez-Bernal1Juan C. Quevedo-Abeledo2Yolanda Fernández-Cladera3Agustín F. González-Rivero4Antonia de Vera-González5Iñigo de la Rua-Figueroa6Raquel López-Mejias7Federico Díaz-González8Federico Díaz-González9Miguel Á. González-Gay10Miguel Á. González-Gay11Miguel Á. González-Gay12Iván Ferraz-Amaro13Iván Ferraz-Amaro14Division of Rheumatology, Hospital Universitario de Canarias, Tenerife, SpainDivision of Central Laboratory, Hospital Universitario de Canarias, Tenerife, SpainDivision of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, SpainDivision of Central Laboratory, Hospital Universitario de Canarias, Tenerife, SpainDivision of Central Laboratory, Hospital Universitario de Canarias, Tenerife, SpainDivision of Central Laboratory, Hospital Universitario de Canarias, Tenerife, SpainDivision of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, SpainEpidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación sanitaria Marqués de Valdecilla (IDIVAL), Santander, SpainDivision of Rheumatology, Hospital Universitario de Canarias, Tenerife, SpainDepartment of Internal Medicine. University of La Laguna (ULL), Tenerife, SpainDivision of Rheumatology, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, SpainUniversity of Cantabria, Instituto de Investigación sanitaria Marqués de Valdecilla (IDIVAL), Santander, SpainCardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaDivision of Rheumatology, Hospital Universitario de Canarias, Tenerife, SpainDepartment of Internal Medicine. University of La Laguna (ULL), Tenerife, SpainBackgroundTo date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics.MethodsNew generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system.ResultsLower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-β2GP, predominantly involving the AL pathway.ConclusionNot only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1167055/fullsystemic lupus erythematosuscomplement systemcomplement pathwaysdisease activitydisease damagedisease profiles
spellingShingle María García-González
Fuensanta Gómez-Bernal
Juan C. Quevedo-Abeledo
Yolanda Fernández-Cladera
Agustín F. González-Rivero
Antonia de Vera-González
Iñigo de la Rua-Figueroa
Raquel López-Mejias
Federico Díaz-González
Federico Díaz-González
Miguel Á. González-Gay
Miguel Á. González-Gay
Miguel Á. González-Gay
Iván Ferraz-Amaro
Iván Ferraz-Amaro
Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
Frontiers in Immunology
systemic lupus erythematosus
complement system
complement pathways
disease activity
disease damage
disease profiles
title Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
title_full Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
title_fullStr Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
title_full_unstemmed Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
title_short Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
title_sort full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
topic systemic lupus erythematosus
complement system
complement pathways
disease activity
disease damage
disease profiles
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1167055/full
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