Cargando…

An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases

High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Inf...

Descripción completa

Detalles Bibliográficos
Autores principales: Bettacchioli, Eléonore, Le Gaffric, Christelle, Mazeas, Margaux, Borghi, Maria Orietta, Frostegard, Johan, Barturen, Guillermo, Makowska, Zuzanna, Babei, Sepideh, Lesche, Ralf, Meroni, Pier Luigi, Alarcon-Riquelme, Marta E., Renaudineau, Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010703/
https://www.ncbi.nlm.nih.gov/pubmed/33817614
http://dx.doi.org/10.1016/j.jtauto.2021.100090
_version_ 1783673111945674752
author Bettacchioli, Eléonore
Le Gaffric, Christelle
Mazeas, Margaux
Borghi, Maria Orietta
Frostegard, Johan
Barturen, Guillermo
Makowska, Zuzanna
Babei, Sepideh
Lesche, Ralf
Meroni, Pier Luigi
Alarcon-Riquelme, Marta E.
Renaudineau, Yves
author_facet Bettacchioli, Eléonore
Le Gaffric, Christelle
Mazeas, Margaux
Borghi, Maria Orietta
Frostegard, Johan
Barturen, Guillermo
Makowska, Zuzanna
Babei, Sepideh
Lesche, Ralf
Meroni, Pier Luigi
Alarcon-Riquelme, Marta E.
Renaudineau, Yves
author_sort Bettacchioli, Eléonore
collection PubMed
description High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Information regarding clinical parameters, disease activity, medications, autoantibodies (Ab) and the interferon α and/or γ scores were recorded. Among SAD patients, 28.4% had raised total FLC (from 12% in RA to 30% in SLE and APS) with a normal kappa/lambda ratio. Total FLC levels were significantly higher in SAD with inflammation, active disease in SLE and SjS, and an impaired pulmonary functional capacity in SSc, while independent from kidney impairment, infection, cancer and treatment. Total FLC concentrations were positively correlated among the 10/17 (58.8%) autoantibodies (Ab) tested with anti-RNA binding protein Ab (SSB, SSA-52/60 kDa, Sm, U1-RNP), anti-dsDNA/nucleosome Ab, rheumatoid factor and negatively correlated with complement fractions C3/C4. Finally, examination of interferon (IFN) expression as a potential driver of FLC overexpression was tested showing an elevated level of total FLC among patients with a high IFNα and IFNγ Kirou's score, a strong IFN modular score, and the detection in the sera of B-cell IFN dependent factors, such as TNF-R1/TNFRSF1A and CXCL10/IP10. In conclusion, an elevated level of FLC, in association with a strong IFN signature, defines a subgroup of SAD patients, including those without renal affectation, characterized by increased disease activity, autoreactivity, and complement reduction.
format Online
Article
Text
id pubmed-8010703
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-80107032021-04-02 An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases Bettacchioli, Eléonore Le Gaffric, Christelle Mazeas, Margaux Borghi, Maria Orietta Frostegard, Johan Barturen, Guillermo Makowska, Zuzanna Babei, Sepideh Lesche, Ralf Meroni, Pier Luigi Alarcon-Riquelme, Marta E. Renaudineau, Yves J Transl Autoimmun Research paper High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Information regarding clinical parameters, disease activity, medications, autoantibodies (Ab) and the interferon α and/or γ scores were recorded. Among SAD patients, 28.4% had raised total FLC (from 12% in RA to 30% in SLE and APS) with a normal kappa/lambda ratio. Total FLC levels were significantly higher in SAD with inflammation, active disease in SLE and SjS, and an impaired pulmonary functional capacity in SSc, while independent from kidney impairment, infection, cancer and treatment. Total FLC concentrations were positively correlated among the 10/17 (58.8%) autoantibodies (Ab) tested with anti-RNA binding protein Ab (SSB, SSA-52/60 kDa, Sm, U1-RNP), anti-dsDNA/nucleosome Ab, rheumatoid factor and negatively correlated with complement fractions C3/C4. Finally, examination of interferon (IFN) expression as a potential driver of FLC overexpression was tested showing an elevated level of total FLC among patients with a high IFNα and IFNγ Kirou's score, a strong IFN modular score, and the detection in the sera of B-cell IFN dependent factors, such as TNF-R1/TNFRSF1A and CXCL10/IP10. In conclusion, an elevated level of FLC, in association with a strong IFN signature, defines a subgroup of SAD patients, including those without renal affectation, characterized by increased disease activity, autoreactivity, and complement reduction. Elsevier 2021-03-02 /pmc/articles/PMC8010703/ /pubmed/33817614 http://dx.doi.org/10.1016/j.jtauto.2021.100090 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research paper
Bettacchioli, Eléonore
Le Gaffric, Christelle
Mazeas, Margaux
Borghi, Maria Orietta
Frostegard, Johan
Barturen, Guillermo
Makowska, Zuzanna
Babei, Sepideh
Lesche, Ralf
Meroni, Pier Luigi
Alarcon-Riquelme, Marta E.
Renaudineau, Yves
An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases
title An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases
title_full An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases
title_fullStr An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases
title_full_unstemmed An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases
title_short An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases
title_sort elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010703/
https://www.ncbi.nlm.nih.gov/pubmed/33817614
http://dx.doi.org/10.1016/j.jtauto.2021.100090
work_keys_str_mv AT bettacchiolieleonore anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT legaffricchristelle anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT mazeasmargaux anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT borghimariaorietta anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT frostegardjohan anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT barturenguillermo anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT makowskazuzanna anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT babeisepideh anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT lescheralf anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT meronipierluigi anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT alarconriquelmemartae anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT renaudineauyves anelevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT bettacchiolieleonore elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT legaffricchristelle elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT mazeasmargaux elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT borghimariaorietta elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT frostegardjohan elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT barturenguillermo elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT makowskazuzanna elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT babeisepideh elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT lescheralf elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT meronipierluigi elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT alarconriquelmemartae elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases
AT renaudineauyves elevatedpolyclonalfreelightchainlevelreflectsastronginterferonsignatureinpatientswithsystemicautoimmunediseases