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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.

Draborg AH, Lydolph MC, Westergaard M, Olesen Larsen S, Nielsen CT, Duus K, Jacobsen S, Houen G - PLoS ONE (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Concentration of serum FLCs in SLE patients and healthy controls.Total FLC (A), λFLC (B) and κFLC (C) levels in SLE patients (n = 45) and healthy controls (n = 40) measured by quantitative nephelometry. SLE patients suffering from renal insufficiency (eGFR<60 ml/min/1.73m2) were excluded. Middle horizontal bars represent median and statistical significant differences are indicated with *, ** or *** for p-values less than 0.05, 0.01 or 0.001. p-values for comparison of FLC levels in SLE patients and healthy controls are <0.0001. Maximum and minimum values of the normal ranges of λFLCs and κFLCs are indicated on the y-axis as dotted lines. FLCs—free light chains, SLE—systemic lupus erythematosus.
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pone.0138753.g001: Concentration of serum FLCs in SLE patients and healthy controls.Total FLC (A), λFLC (B) and κFLC (C) levels in SLE patients (n = 45) and healthy controls (n = 40) measured by quantitative nephelometry. SLE patients suffering from renal insufficiency (eGFR<60 ml/min/1.73m2) were excluded. Middle horizontal bars represent median and statistical significant differences are indicated with *, ** or *** for p-values less than 0.05, 0.01 or 0.001. p-values for comparison of FLC levels in SLE patients and healthy controls are <0.0001. Maximum and minimum values of the normal ranges of λFLCs and κFLCs are indicated on the y-axis as dotted lines. FLCs—free light chains, SLE—systemic lupus erythematosus.

Mentions: Sera from 45 SLE patients and 40 healthy controls were examined by quantitative nephelometry for concentration of κFLCs and λFLCs. As illustrated in Fig 1A, a significantly elevated concentration of total serum FLCs was found in SLE patients compared to healthy controls (p<0.0001). The median total FLC concentration was 46.4 mg/L in SLE patients compared to a median level of 27.6 mg/L in healthy controls. Similar results were obtained when examining the λFLC and κFLC levels individually (Fig 1B and 1C), with significantly higher concentrations in SLE patients compared to healthy controls (p<0.0001 in both cases). The median value of λFLCs was 25.3 mg/L in SLE patients and 14.5 mg/L in healthy controls, and the median value was 22.5 mg/L and 13.1 mg/L of κFLCs in SLE patients and healthy controls, respectively.


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.

Draborg AH, Lydolph MC, Westergaard M, Olesen Larsen S, Nielsen CT, Duus K, Jacobsen S, Houen G - PLoS ONE (2015)

Concentration of serum FLCs in SLE patients and healthy controls.Total FLC (A), λFLC (B) and κFLC (C) levels in SLE patients (n = 45) and healthy controls (n = 40) measured by quantitative nephelometry. SLE patients suffering from renal insufficiency (eGFR<60 ml/min/1.73m2) were excluded. Middle horizontal bars represent median and statistical significant differences are indicated with *, ** or *** for p-values less than 0.05, 0.01 or 0.001. p-values for comparison of FLC levels in SLE patients and healthy controls are <0.0001. Maximum and minimum values of the normal ranges of λFLCs and κFLCs are indicated on the y-axis as dotted lines. FLCs—free light chains, SLE—systemic lupus erythematosus.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4581754&req=5

pone.0138753.g001: Concentration of serum FLCs in SLE patients and healthy controls.Total FLC (A), λFLC (B) and κFLC (C) levels in SLE patients (n = 45) and healthy controls (n = 40) measured by quantitative nephelometry. SLE patients suffering from renal insufficiency (eGFR<60 ml/min/1.73m2) were excluded. Middle horizontal bars represent median and statistical significant differences are indicated with *, ** or *** for p-values less than 0.05, 0.01 or 0.001. p-values for comparison of FLC levels in SLE patients and healthy controls are <0.0001. Maximum and minimum values of the normal ranges of λFLCs and κFLCs are indicated on the y-axis as dotted lines. FLCs—free light chains, SLE—systemic lupus erythematosus.
Mentions: Sera from 45 SLE patients and 40 healthy controls were examined by quantitative nephelometry for concentration of κFLCs and λFLCs. As illustrated in Fig 1A, a significantly elevated concentration of total serum FLCs was found in SLE patients compared to healthy controls (p<0.0001). The median total FLC concentration was 46.4 mg/L in SLE patients compared to a median level of 27.6 mg/L in healthy controls. Similar results were obtained when examining the λFLC and κFLC levels individually (Fig 1B and 1C), with significantly higher concentrations in SLE patients compared to healthy controls (p<0.0001 in both cases). The median value of λFLCs was 25.3 mg/L in SLE patients and 14.5 mg/L in healthy controls, and the median value was 22.5 mg/L and 13.1 mg/L of κFLCs in SLE patients and healthy controls, respectively.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus