Abstract
ObjectiveIn this study, we examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore, FLCs’ association with Epstein-Barr virus (EBV) antibodies was examined.MethodsUsing a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations of serum FLCs due to decreased clearance.ResultsSerum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (p<0.0001) also after adjusting for Ig levels (p<0.0001). The concentration of serum FLCs correlated with a global disease activity (SLE disease activity index (SLEDAI)) score of the SLE patients (r = 0.399, p = 0.007). Furthermore, concentrations of FLCs correlated with titers of dsDNA antibodies (r = 0.383, p = 0.009), and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients. Total immunoglobulin (IgG and IgA) concentrations correlated with FLC concentrations and elevated FLC levels were additionally shown to associate with the inflammatory marker C-reactive protein and also with complement consumption determined by low C4 in SLE patients. Collectively, results indicated that elevated serum FLCs reflects increased B cell activity in relation to inflammation. SLE patients had an increased seropositivity of EBV-directed antibodies that did not associate with elevated FLC concentrations. An explanation for this could be that serum FLC concentrations reflect the current EBV activity (reactivation) whereas EBV-directed antibodies reflect the extent of previous infection/reactivations.ConclusionSLE patients have elevated concentrations of serum FLCs that correlate with global disease activity scores and especially serologic markers for active disease. These findings are suggestive of circulating FLCs having potential as a new supplementary serologic biomarker in SLE.
Highlights
Systemic lupus erythematosus (SLE) is an important autoimmune disease with a prevalence of 20–150 cases per 100.000 [1,2], and typically presents in women (90% of cases) in the reproductive age
Concentrations of Free light chains (FLCs) correlated with titers of double-stranded DNA (dsDNA) antibodies (r = 0.383, p = 0.009), and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients
Elevated Concentrations of Serum FLCs in SLE Patients concentrations and elevated FLC levels were shown to associate with the inflammatory marker C-reactive protein and with complement consumption determined by low C4 in SLE patients
Summary
Systemic lupus erythematosus (SLE) is an important autoimmune disease with a prevalence of 20–150 cases per 100.000 [1,2], and typically presents in women (90% of cases) in the reproductive age. Free light chains (FLCs) are released to the circulation; κFLCs are released as either monomers or dimers and λFLCs are released as dimers. The serum FLCs are rapidly catabolized by the kidneys with a half life in the circulation of 2–4 hours for κFLCs and 3–6 hours for λFLCs. The normal concentration of FLCs in serum and urine is kept at low levels due to the kidneys massive capacity for clearing of serum FLCs (10–30 grams/day). In individuals with normal renal function, increased concentrations of serum FLCs are presumably a result of increased plasma cell activity [11,12,13]. Some SLE patients suffer from glomerulonephritis and renal insufficiency and as a consequence these patients presumably have decreased clearance of FLCs and thereby an elevated concentration in the circulation
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