RT Journal Article
T1 An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases.
A1 Bettacchioli, Eléonore
A1 Le Gaffric, Christelle
A1 Mazeas, Margaux
A1 Borghi, Maria Orietta
A1 Frostegard, Johan
A1 Barturen, Guillermo
A1 Makowska, Zuzanna
A1 Babei, Sepideh
A1 Lesche, Ralf
A1 PRECISESADS Clinical Consortium, 
A1 Meroni, Pier Luigi
A1 Alarcon-Riquelme, Marta E
A1 Renaudineau, Yves
K1 APS, primary antiphospholipid syndrome
K1 AUC, area under the curve
K1 Ab, autoantibody
K1 Autoantibodies
K1 Autoimmune diseases
K1 CCP, cyclic citrulinated peptide
K1 CXCL10, C-X-C motif chemokine 10
K1 F, female
K1 FLC, free light chains
K1 Free light chains
K1 HC, healthy controls
K1 IFN, interferon
K1 Interferon signature
K1 M, male
K1 MCTD, mixed connective tissue disease
K1 MDA, malondialdehyde
K1 NK, natural killer
K1 PC, phosphorylcholine
K1 RA, rheumatoid arthritis
K1 RF, rheumatoid factor
K1 RNP, ribonucleoprotein
K1 ROC, Receiver Operating Characteristics
K1 SAD, systemic autoimmune diseases
K1 SD, standard deviation
K1 SLE, systemic lupus erythematosus
K1 Scl, systemic sclerosis
K1 SjS, Sjögren's syndrome
K1 TH1, T helper type 1
K1 TNF-R1, tumor necrosis factor receptor 1
K1 UCTD, undetermined connective tissue disease
K1 VAS, visual analogical scale
K1 κ, kappa
K1 λ, lambda
AB 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.
YR 2021
FD 2021-03-02
LK https://hdl.handle.net/10668/28379
UL https://hdl.handle.net/10668/28379
LA en
DS RISalud
RD Apr 12, 2025