Serum immunoglobulin free light chain levels in systemic autoimmune rheumatic diseases

Abstract

Summary Several reports have highlighted the abnormal increments of serum immunoglobulin free light chains (FLCs) in the course of systemic autoimmune rheumatic diseases (SARD), but a comparative analysis among different conditions is still lacking. A strong association between elevated FLC and hepatitis C virus (HCV)-related mixed cryoglobulinaemia (HCVMC) has been well established. Here, we aimed to analyse serum FLC levels in patients with four different SARD in comparison with HCVMC. Using a turbidimetric assay, free κ and λ chains were quantified in sera from 198 SARD patients (37 rheumatoid arthritis, RA; 47 systemic lupus erythematosus, SLE; 52 anti-phospholipid syndrome, APS; 62 primary Sjogren's syndrome, pSS), 62 HCVMC and 50 healthy blood donors (HD). All patient groups showed increased κ levels when compared to HD: 33·5 ± 2·6 mg/l in HCVMC, 26·7 ± 2·3 mg/l in RA, 29·7 ± 1·9 mg/l in SLE, 23·8 ± 1·1 mg/l in APS, 24·2 ± 1·1 mg/l in pSS; 10·1 ± 0·6 mg/l in HD. Free λ levels displayed a significant increase only for HCVMC (20·4 ± 1·4 mg/l) and SLE (18·4 ± 1·0 mg/l) compared to HD (13·6 ± 0·9 mg/l). The increase of κ compared to λ takes into account a κ /λ ratio of 1·6 for all groups. Our results substantially analyse and strengthen the association between FLC and SARD focusing the questions regarding their role in the pathogenesis and diagnosis of human diseases. Unfortunately, the biochemical differences distinguishing normal from pathological FLC have not been identified. Production of different isotypes is probably connected to still-unknown pathways.

High κ free light chain is a potential biomarker for double seronegative and ocular myasthenia gravis

“…The exclusion criteria were a diagnosis of plasma cell dyscrasia disorders, a diagnosis or suspicion of another chronic inflammatory condition known to be associated with increased serum levels of FLC (such as rheumatoid arthritis, systemic sclerosis, Sjögren syndrome, and systemic lupus erythematosus), 10 , 14 a glomerular filtration rate of <60 mL/min/1.73 m 2 , and treatment with plasmapheresis for the past 3 months. We recruited healthy individuals to serve as the control group to test whether FLC levels are high in the sera of patients with MG.…”

“…In conditions in which the only diagnostic support for MG is a high κ FLC level, and after ruling out other disorders that are associated with high κ FLC levels, it would be appropriate to consider performing hematologic and immunologic tests for these disorder markers to rule them out. Because we did not assess the association between FLC levels with disease activity, severity, and response to therapy, we cannot comment on the use of FLC as a biomarker for MG activity, as reported in other autoimmune diseases, 9,10,14,25 or for the possibility of its being a marker of response to therapy. Further investigation is needed to study these questions.…”

“…9 An increase in free light chain (FLC) production has been reported in several autoimmune diseases. [11][12][13][14][15][16][17] To the best of our knowledge, only 1 study has evaluated FLC levels in MG, and it reported an elevation of both κ FLC and λ FLC in their 34 study patients. 18 We hypothesized that κ FLC and λ FLC levels may be biomarkers for MG, especially for SN-MG for which diagnosis can be difficult.…”

Cryoglobulins: Identification, classification, and novel biomarkers of mysterious proteins

“…Patients at risk of disease flare could be monitored with biomarkers to allow early intervention and possibly to reduce end-organ damage and mortality. Increased levels of biomarkers have also been described in the course of autoimmune diseases and are correlated with disease activity, facilitating the best choice of a therapeutic scheme [38] , [39] .…”

Assessment of immunoglobulins free light chains in serum and urine of patients with system sclerosis: novel biomarkers for activity disease

“…Therefore, in subjects with normal kidney function, their serum levels can be considered as a direct biomarker of B cell activity, which explains the growing interest of clinicians. More important, the well-demonstrated FLC contribution to inflammation in experimental disease models sparked a new light into their pathogenic role in different chronic autoimmune-based inflammatory diseases [4]. An increased level of polyclonal sFLC, described in several autoimmune diseases (ADs), may represent a reliable potential biomarker of disease evolution or remission [5].…”