Serum immunoglobulin free light chains are sensitive biomarkers for monitoring disease activity and treatment response in primary Sjögren's syndrome

Rheumatology (Oxford). 2018 Oct 1;57(10):1812-1821. doi: 10.1093/rheumatology/key180.

Abstract

Objectives: Serum immunoglobulin free light chains (FLCs) are frequently elevated in B-cell-mediated autoimmune diseases, including primary SS (pSS). The objective of this study was to assess if serum FLCs can contribute to classification, mucosa-associated lymphoid tissue (MALT) lymphoma detection, monitoring of disease activity and treatment response in pSS.

Methods: Serum samples of 100 consecutive patients suspected of pSS were included. Forty-five patients fulfilled ACR-EULAR criteria for pSS. Additionally, samples of 17 pSS patients with MALT lymphoma and longitudinal samples of pSS patients treated with rituximab (n = 20), placebo (n = 10) or abatacept (n = 15) were included. Serum FLCκ/FLCλ was measured by nephelometry or turbidimetry.

Results: At diagnosis, FLCκ and FLCλ serum levels were significantly higher in pSS compared with non-SS sicca patients. The FLCκ/FLCλ ratio was abnormal in 11% of pSS patients. In established MALT-pSS patients, without recent rituximab treatment (n = 12), 50% had abnormal FLCκ/FLCλ ratios. FLC measurement had no additional value for pSS classification, compared with IgG and anti-SSA. FLC levels correlated significantly with systemic disease activity, assessed by EULAR SS Disease Activity Index (ESSDAI) and clinical ESSDAI, both cross-sectionally and longitudinally following treatment. Treatment with rituximab or abatacept significantly lowered FLC levels. FLCs show a large sensitivity to change and relative changes induced by treatment were higher compared with IgG.

Conclusion: Serum FLCs are elevated in pSS, and abnormal FLCκ/FLCλ ratios may be indicative for the presence of MALT lymhoma. FLC levels can be used as a biomarker for systemic disease activity and monitoring treatment responses. FLCs are sensitive to change and have more favorable kinetics than IgG.

MeSH terms

  • Abatacept / therapeutic use
  • Adult
  • Biomarkers / blood
  • Female
  • Humans
  • Immunoglobulin Light Chains / blood*
  • Immunologic Factors / therapeutic use*
  • Longitudinal Studies
  • Lymphoma, B-Cell, Marginal Zone / blood*
  • Lymphoma, B-Cell, Marginal Zone / immunology
  • Male
  • Middle Aged
  • Monitoring, Immunologic
  • Randomized Controlled Trials as Topic
  • Rituximab / therapeutic use
  • Sjogren's Syndrome / blood*
  • Sjogren's Syndrome / drug therapy
  • Sjogren's Syndrome / immunology
  • Treatment Outcome

Substances

  • Biomarkers
  • Immunoglobulin Light Chains
  • Immunologic Factors
  • Rituximab
  • Abatacept