Bettacchioli, EléonoreLe Gaffric, ChristelleMazeas, MargauxBorghi, Maria OriettaFrostegard, JohanBarturen, GuillermoMakowska, ZuzannaBabei, SepidehLesche, RalfPRECISESADS Clinical ConsortiumMeroni, Pier LuigiAlarcon-Riquelme, Marta ERenaudineau, Yves2025-01-072025-01-072021-03-02https://hdl.handle.net/10668/28379High 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/APS, primary antiphospholipid syndromeAUC, area under the curveAb, autoantibodyAutoantibodiesAutoimmune diseasesCCP, cyclic citrulinated peptideCXCL10, C-X-C motif chemokine 10F, femaleFLC, free light chainsFree light chainsHC, healthy controlsIFN, interferonInterferon signatureM, maleMCTD, mixed connective tissue diseaseMDA, malondialdehydeNK, natural killerPC, phosphorylcholineRA, rheumatoid arthritisRF, rheumatoid factorRNP, ribonucleoproteinROC, Receiver Operating CharacteristicsSAD, systemic autoimmune diseasesSD, standard deviationSLE, systemic lupus erythematosusScl, systemic sclerosisSjS, Sjögren's syndromeTH1, T helper type 1TNF-R1, tumor necrosis factor receptor 1UCTD, undetermined connective tissue diseaseVAS, visual analogical scaleκ, kappaλ, lambdaresearch article33817614open access10.1016/j.jtauto.2021.1000902589-9090PMC8010703https://doi.org/10.1016/j.jtauto.2021.100090https://pmc.ncbi.nlm.nih.gov/articles/PMC8010703/pdf