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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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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 |
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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 |
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