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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

Correlation between serum FLC concentrations and SLEDAI scores in SLE patients with high CRP.Correlation between SLEDAI scores and total FLC, λFLC and κFLC levels in high CRP SLE patients (A) (n = 30) and in low CRP SLE patients (B) (n = 15). A: High CRP SLE patients. r-values are 0.506 (p = 0.004), 0.500 (p = 0.005) and 0.453 (p = 0.012) regarding total FLC, λFLC and κFLC levels, respectively. B: Low CRP SLE patients. r-values are 0.246 (p = 0.378), 0.393 (p = 0.148) and -0.056 (p = 0.844) regarding total FLC, λFLC and κFLC levels, respectively. FLCs—free light chains, SLE—systemic lupus erythematosus, SLEDAI—SLE disease activity index, CRP—C-reactive protein.
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pone.0138753.g008: Correlation between serum FLC concentrations and SLEDAI scores in SLE patients with high CRP.Correlation between SLEDAI scores and total FLC, λFLC and κFLC levels in high CRP SLE patients (A) (n = 30) and in low CRP SLE patients (B) (n = 15). A: High CRP SLE patients. r-values are 0.506 (p = 0.004), 0.500 (p = 0.005) and 0.453 (p = 0.012) regarding total FLC, λFLC and κFLC levels, respectively. B: Low CRP SLE patients. r-values are 0.246 (p = 0.378), 0.393 (p = 0.148) and -0.056 (p = 0.844) regarding total FLC, λFLC and κFLC levels, respectively. FLCs—free light chains, SLE—systemic lupus erythematosus, SLEDAI—SLE disease activity index, CRP—C-reactive protein.

Mentions: SLE patients stratified according to their concentrations of CRP showed that SLE patients with high CRP (>1 mg/l)(n = 30) had significantly higher serum λFLC concentrations compared to the SLE patients with low CRP (<1 mg/l) (n = 15) (p = 0.057, p = 0.050 and p = 0.059, regarding concentrations of total FLC, λFLC and κFLC, respectively) (results not shown). A positive correlation was obtained between FLC concentrations and SLEDAI scores for high CRP SLE patients (SLEDAI range: 0–21, median: 4) (Fig 8A) (r-values of 0.506 (p = 0.004), 0.500 (p = 0.005) and 0.453 (p = 0.012), regarding concentrations of total FLC, λFLC and κFLC, respectively), but not between FLC concentrations and SLEDAI scores for low CRP SLE patients (SLEDAI range: 0–12, median: 4) (Fig 8B) (r-values of 0.246 (p = 0.378), 0.393 (p = 0.148) and -0.056 (p = 0.844), regarding concentrations of total FLC, λFLC and κFLC, 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)

Correlation between serum FLC concentrations and SLEDAI scores in SLE patients with high CRP.Correlation between SLEDAI scores and total FLC, λFLC and κFLC levels in high CRP SLE patients (A) (n = 30) and in low CRP SLE patients (B) (n = 15). A: High CRP SLE patients. r-values are 0.506 (p = 0.004), 0.500 (p = 0.005) and 0.453 (p = 0.012) regarding total FLC, λFLC and κFLC levels, respectively. B: Low CRP SLE patients. r-values are 0.246 (p = 0.378), 0.393 (p = 0.148) and -0.056 (p = 0.844) regarding total FLC, λFLC and κFLC levels, respectively. FLCs—free light chains, SLE—systemic lupus erythematosus, SLEDAI—SLE disease activity index, CRP—C-reactive protein.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0138753.g008: Correlation between serum FLC concentrations and SLEDAI scores in SLE patients with high CRP.Correlation between SLEDAI scores and total FLC, λFLC and κFLC levels in high CRP SLE patients (A) (n = 30) and in low CRP SLE patients (B) (n = 15). A: High CRP SLE patients. r-values are 0.506 (p = 0.004), 0.500 (p = 0.005) and 0.453 (p = 0.012) regarding total FLC, λFLC and κFLC levels, respectively. B: Low CRP SLE patients. r-values are 0.246 (p = 0.378), 0.393 (p = 0.148) and -0.056 (p = 0.844) regarding total FLC, λFLC and κFLC levels, respectively. FLCs—free light chains, SLE—systemic lupus erythematosus, SLEDAI—SLE disease activity index, CRP—C-reactive protein.
Mentions: SLE patients stratified according to their concentrations of CRP showed that SLE patients with high CRP (>1 mg/l)(n = 30) had significantly higher serum λFLC concentrations compared to the SLE patients with low CRP (<1 mg/l) (n = 15) (p = 0.057, p = 0.050 and p = 0.059, regarding concentrations of total FLC, λFLC and κFLC, respectively) (results not shown). A positive correlation was obtained between FLC concentrations and SLEDAI scores for high CRP SLE patients (SLEDAI range: 0–21, median: 4) (Fig 8A) (r-values of 0.506 (p = 0.004), 0.500 (p = 0.005) and 0.453 (p = 0.012), regarding concentrations of total FLC, λFLC and κFLC, respectively), but not between FLC concentrations and SLEDAI scores for low CRP SLE patients (SLEDAI range: 0–12, median: 4) (Fig 8B) (r-values of 0.246 (p = 0.378), 0.393 (p = 0.148) and -0.056 (p = 0.844), regarding concentrations of total FLC, λFLC and κFLC, 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