Session Type: Abstract Submissions (ACR)
Background/Purpose: Chronic and hyper-stimulated B cells are characteristics commonly found in patients with systemic lupus erythematosus (SLE). Due to the complexity and variability observed during the course of the disease there is a paucity of suitable biomarkers and those available do not always reflect disease activity. Polyclonal serum free light chains (FLC), a marker of immune status and renal function, have been reported to be elevated in SLE. The aim here was to compare FLC levels with both routine biomarkers and the British Isles Lupus Assessment Group Index (BILAG) for disease activity in a prospectively collected SLE cohort.
Methods: Combined FLC (FLCκ + FLCλ= cFLC; Combylite; The Binding Site Group Ltd), IgG, IgA, IgM and Cystatin C (The Binding Site Group Ltd) were measured in sera from 62 patients who met the revised ACR criteria for the classification of SLE. Results were compared to conventional biomarkers of SLE disease activity, including anti-dsDNA antibodies, C3, lymphocyte count and erythrocyte sedimentation rate (ESR). Serologically active disease was defined as patients with elevated anti-dsDNA antibody levels (>50 IU/ml) and reduced C3 (<0.9g/L). BILAG was used to assess disease activity; clinically active disease was defined as an A or B score in any organ system. Statistical analysis (Mann Whitney U test and Spearman correlations) was performed using SPSS v21.
Results: The median age was 43 years (range: 21-86); 90% were female and 50% were Caucasian. The median cFLC concentration was 31.86mg/L (IQR: 22.27-58.17; median concentration in a healthy population: 20mg/L). Moderate correlations were observed between cFLC vs: ESR (r: 0.5, p<0.001), cystatin C (r: 0.41, p=0.002), IgG (r: 0.6, p<0.001) and IgA (r: 0.6, p<0.001). A weak correlation was seen between cFLC and anti-dsDNA antibodies (r: 0.3, p=0.02), but there was no association with C3 (r: -0.2, p=0.15), lymphocyte count (r: -0.1, p=0.36) or IgM (r: 0.03, p=0.82). In patients with serologically active disease (N=19, 32%), median cFLC levels were significantly elevated: 58.1mg/L (34.67-80.9) vs 28.9mg/L (20.56-45.09), p=0.02. Using the BILAG score, cFLC levels were elevated in patients with clinically active (N=26, 42%) vs inactive disease (N=36, 58%): 39.6mg/L (IQR: 25.3-80.9) vs 29.7mg/L (IQR: 19.3-49.3), p=0.05. Anti-dsDNA antibody levels were also elevated: 258 IU/ml (16-644.5) vs 45 IU/ml (10-181), p=0.04; however, there was no significant difference in the levels of C3 (p=0.32), ESR (p=0.65), IgG (p=0.31), IgA (p=0.27), IgM (p=0.68), or cystatin C (p=0.09) between the two groups.
Conclusion: cFLC concentrations are likely to reflect B cell activity and therefore represent attractive markers in SLE. In this study, elevated levels correlated with disease activity supporting this hypothesis, however further work is required to evaluate the usefulness of this observation and to determine how cFLC may be used to monitor disease progression.
L. K. Assi,
The Binding Site Group Ltd,
R. G. Hughes,
The Binding Site Group Ltd,
D. A. Isenberg,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-combined-serum-free-light-chains-are-associated-with-active-disease-in-systemic-lupus-erythematosus/