Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay

Faint, J. M. et al. (2014) Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay. Clinical Chemistry and Laboratory Medicine, 52(11), pp. 1605-1613. (doi: 10.1515/cclm-2014-0279) (PMID:24926626)

Abstract

Background: Elevated polyclonal serum free light chain (FLC) levels have been associated with increased mortality and disease activity in many conditions. Currently, polyclonal FLC quantification requires summation of individual FLCκ and FLCλ assays. Here we present a single assay for combined FLC (cFLC, Combylite™) which reduces assay time and eliminates potential imprecision errors incurred by summating FLC assays (ΣFLC).

Methods: Sheep FLCκ- and FLCλ-specific antibodies were conjugated to latex microparticles to quantify FLCκ and FLCλ in a single assay. Combylite results were compared to ΣFLC (Freelite®) in 132 healthy controls and 1127 patient samples. The utility of cFLC for predicting all-cause mortality in a haematological referral population was evaluated.

Results: cFLC and ΣFLC results were highly concordant (Passing-Bablok equation y=0.98x–1.59 mg/L, R2=0.96). Combylite assay imprecision was low at concentrations around the upper normal range [coefficient of variation (CV) 5.5%, 54 mg/L] and the upper limit of the measuring range (CV 5.5%, 170 mg/L). cFLC levels were significantly raised in disease states compared with healthy controls. Additionally, cFLC >65 mg/L was associated with shorter overall survival in a haematological referral population (hazard ratio=4.5, p<0.001).

Conclusions: cFLC values obtained using Combylite were comparable to ΣFLC results over a wide concentration range, were elevated in diseases characterised by B cell activation and were associated with increased mortality in a haematological referral population. These observations indicate the Combylite assay has value for investigating the role of B cell activation in disparate disease groups and could be considered as a surrogate indication of B cell function.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jackson, Dr Colette
• Authors: Faint, J. M., Basu, S., Sutton, D., Showell, P. J., Kalra, P. A., Gunson, B. K., Jackson, C. E., Mushtaq, A., Assi, L. K., Carr-Smith, H. D., Cockwell, P., and Harding, S. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Clinical Chemistry and Laboratory Medicine
• Publisher: Walter de Gruyter GmbH
• ISSN: 1434-6621
• ISSN (Online): 1437-4331