Date: Sunday, November 5, 2017
Session Title: Sjögren's Syndrome Poster I: Translational Research
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
During immunoglobulin synthesis in B-cells, kappa and lambda light chains are produced in excess compared to heavy chains, and the surplus of light chains are secreted into serum as free light chains (FLC). Compared to healthy individuals, elevated serum levels of polyclonal FLCs are seen in autoimmune diseases associated with increased B-cell activation, including primary Sjögren’s syndrome (pSS). In pSS, serum FLC levels correlate with IgG, rheumatoid factor and systemic disease activity.1 However, the clinical relevance of serum FLC levels as biomarker in pSS remains unclear. The objective of this study is to assess if I) FLCs are already elevated at the time of diagnosis, II) FLC levels can discriminate non-SS sicca from pSS patients, and III) FLCs can be used to monitor treatment response.
Serum samples of 102 consecutive patients referred to our expertise center for suspicion of pSS were included. Patients were classified by a panel of 3 clinical experts as non-SS sicca, incomplete pSS or pSS and fulfillment of ACR-EULAR criteria for pSS was assessed. Longitudinal serum samples of pSS patients treated with rituximab (n=20) or abatacept (n=15) were also included. Kappa (κ) and lambda (λ) FLCs were measured in serum by the Freelite assay (Binding Site, UK). Area under the ROC curve (AUC) was used to assess the ability of serum FLC levels to predict a pSS diagnosis. Generalized estimating equations were used to measure changes during treatment.
At the time of diagnosis, FLCκ and FLCλ serum levels were significantly higher in pSS patients compared to non-SS sicca patients (FLCκ: median (IQR)=29 (17-39) vs. 15 (11-17) mg/L, p<0.001; FLCλ: 27 (18-34) vs. 15 (13-18) mg/L, p<0.001). The κ/λ ratio was slightly increased in pSS compared to non-SS sicca patients (p=0.045). FLCκ and FLCλ both showed good accuracy to discriminate pSS from non-SS (FLCκ: AUC=0.806, 95% CI=0.708-0.904; FLCλ: AUC=0.802, 95% CI=0.705-0.899). However, the accuracy of serum IgG was higher (AUC=0.885, 95% CI=0.811-0.959). Interestingly, FLCκ was also elevated (>20 mg/L) in 4/9 incomplete pSS patients. In two of them, also FLCλ was elevated (>32 mg/L). In patients fulfilling ACR-EULAR criteria, FLCκ and FLCλ levels correlated with systemic disease activity, assessed by EULAR Sjögren’s syndrome disease activity index (FLCκ: Spearman’s ρ=0.282, p=0.004; FLCλ: ρ=0.321, p=0.001). Treatment with rituximab significantly lowered FLCκ and FLCλ levels (p<0.001 for both). Treatment with abatacept also reduced FLCκ and FLCλ levels, although to a smaller extent (p=0.006 and p=0.087, respectively).
Serum FLCs are elevated in pSS patients at the time of diagnosis and can discriminate non-SS sicca from pSS. FLCκ is already elevated in a large part of the incomplete SS patients and may serve as an early diagnostic biomarker. Furthermore, serum FLC levels can be used to monitor the effect of treatment on B-cell activity and may be more sensitive to change than serum IgG, because of a shorter half-life.
Gottenberg et al., Ann Rheum Dis 2007;66:23-7.
To cite this abstract in AMA style:Verstappen GM, Bijzet J, van Nimwegen JF, van Ginkel MS, Vissink A, Bootsma H, Kroese FGM. Clinical Relevance of Serum Free Light Chain Level As Biomarker in Primary Sjögren′s Syndrome [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/clinical-relevance-of-serum-free-light-chain-level-as-biomarker-in-primary-sjogren%e2%80%b2s-syndrome/. Accessed June 4, 2020.
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