Serum immunoglobulin free light chain levels in systemic autoimmune rheumatic diseases

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 kappa and lambda 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 kappa levels when compared to HD: 33 center dot 5 +/- 2 center dot 6 mg/l in HCVMC, 26 center dot 7 +/- 2 center dot 3 mg/l in RA, 29 center dot 7 +/- 1 center dot 9 mg/l in SLE, 23 center dot 8 +/- 1 center dot 1 mg/l in APS, 24 center dot 2 +/- 1 center dot 1 mg/l in pSS; 10 center dot 1 +/- 0 center dot 6 mg/l in HD. Free lambda levels displayed a significant increase only for HCVMC (20 center dot 4 +/- 1 center dot 4 mg/l) and SLE (18 center dot 4 +/- 1 center dot 0 mg/l) compared to HD (13 center dot 6 +/- 0 center dot 9 mg/l). The increase of kappa compared to lambda takes into account a kappa /lambda ratio of 1 center dot 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.