Elevation of Serum Immunoglobulin Free Light Chains During the Preclinical Period of Rheumatoid Arthritis

Abstract

Objective Immunoglobulin free light chains (FLCs) represent biomarkers of B-cell activity in rheumatoid arthritis (RA) and are associated with all-cause mortality in the general population. Our objective was to evaluate the relationships of serum FLCs to pre-clinical disease, RA characteristics, and mortality in RA compared to non-RA subjects. Methods A population-based study in Olmsted County, Minnesota, was performed by cross-linking a large cohort in the general population having available serum FLC measurements with established RA incidence and prevalence cohorts. Serum κ, λ, and total FLCs and their trends relative to RA incidence were compared between RA and non-RA subjects. Regression models were used to determine the associations between FLCs, disease characteristics and mortality, testing for differential effects of FLCs on mortality in RA. Results Among 16,609 subjects, 270 fulfilled the criteria for RA at the time of FLC measurement. Mean total FLCs were significantly higher in RA compared to non-RA subjects (4.2 vs. 3.3 mg/dL; p<0.001). FLCs became elevated 3 – 5 years before the clinical onset of RA and remained elevated during follow-up. Polyclonal FLCs were found to predict higher mortality in persons with RA, though elevation to the highest decile had a relatively lower impact on mortality in RA compared to non-RA subjects. Conclusions Elevation of serum FLCs precedes the development of RA and may be useful in monitoring B-cell activity and disease progression. FLCs are confirmed predictors of mortality, though the highest elevations of FLCs have a lower impact on mortality in RA than the general population.

Assessment of serum free light chain levels in healthy adults immediately after marathon running

“…FLCs are important for diagnosing, monitoring and prognosticating multiple myeloma, monoclonal gammopathy of unknown significance (MGUS) and an array of other associated disorders [1]. More recently, the prognostic utility of FLCs in non-neoplastic disorders has been highlighted [2][3][4]. Moreover, the sum of polyclonal κ and λ FLCs, expressed as ∑FLC, has been advocated as a global biomarker of immune activation [5], and is now regarded as a powerful prognostic marker for overall survival in the general population [6].…”

Biological links in periodontitis and rheumatoid arthritis: Discovery via text‐mining PubMed abstracts

“…Down‐regulation of neutrophil apoptotic genes is demonstrated in PD and long established in RA plausibly contributing to prolonged inflammation . Immunoglobulin production and IgG titers are higher in RA, even in the pre‐arthritic phase, being associated with autoantibody production . Severe periodontitis‐affected RA subjects have shown greater anti P. gingivalis IgG and IgM, while emerging evidence also shows heightened immunoglobulin response in RA to the pathobiont P. copri .…”

No Evidence of Systemic Inflammation in Symptomatic Patients With Femoroacetabular Impingement

“…Systemic inflammation was only assessed using a single biomarker, sFLCs, which are produced directly by activated B cells. Although, sFLCs are clinically useful in rheumatoid arthritis, [17][18][19][20] distinct inflammatory pathway to other inflammatory measures, such as CRP. 30…”

“…Serum‐free light chains (sFLCs) are inflammatory markers produced by immune cells of plasma cell lineage, they are renally cleared with a half‐life of 2–5 h. Initial studies have demonstrated the potential of sFLCs as a clinically useful biomarker across various fields . In rheumatoid arthritis, sFLC concentrations correlate with disease activity, and sFLC concentrations are raised 3–5 years before the clinical diagnosis of rheumatoid arthritis . The role of sFLCs has not yet been investigated in FAI or osteoarthritis.…”

“…16 In rheumatoid arthritis, sFLC concentrations correlate with disease activity, [17][18][19] and sFLC concentrations are raised 3-5 years before the clinical diagnosis of rheumatoid arthritis. 20 The role of sFLCs has not yet been investigated in FAI or osteoarthritis.…”