title: Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies.
abstract: OBJECTIVE
  In 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.
  
  
  METHODS
  Using 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.
  
  
  RESULTS
  Serum 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.
  
  
  CONCLUSIONS
  SLE 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.
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Anette H
authors.initials: AH
authors.lastname: Draborg
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Magnus C
authors.initials: MC
authors.lastname: Lydolph
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Westergaard
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Severin
authors.initials: S
authors.lastname: Olesen Larsen
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark; Department of Infectious Diseases and Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christoffer T
authors.initials: CT
authors.lastname: Nielsen
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Duus
authors.affiliation: Department of Infectious Diseases and Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houen
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007249:Inflammation / Q000097:blood* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D000914:Antibodies, Viral; D001323:Autoantibodies; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D003165:Complement System Proteins; D002097:C-Reactive Protein