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.
Keywords: APS, primary antiphospholipid syndrome; AUC, area under the curve; Ab, autoantibody; Autoantibodies; Autoimmune diseases; CCP, cyclic citrulinated peptide; CXCL10, C-X-C motif chemokine 10; F, female; FLC, free light chains; Free light chains; HC, healthy controls; IFN, interferon; Interferon signature; M, male; MCTD, mixed connective tissue disease; MDA, malondialdehyde; NK, natural killer; PC, phosphorylcholine; RA, rheumatoid arthritis; RF, rheumatoid factor; RNP, ribonucleoprotein; ROC, Receiver Operating Characteristics; SAD, systemic autoimmune diseases; SD, standard deviation; SLE, systemic lupus erythematosus; Scl, systemic sclerosis; SjS, Sjögren's syndrome; TH1, T helper type 1; TNF-R1, tumor necrosis factor receptor 1; UCTD, undetermined connective tissue disease; VAS, visual analogical scale; κ, kappa; λ, lambda.
© 2021 The Author(s).