Abstract

Introduction: Recent data suggest that serum monoclonal free light chain ratio (LCR) may have prognostic significance in monoclonal gammopathies. We routinely assay serum free light chains (FLC) in all new patients with a monoclonal gammopathy with the primary aim of identifying patients with a significant level of free light chain. We made a retrospective analysis of these data in order to establish the range of results observed in our patients and to establish a cohort of patients who will be followed up to evaluate the prognostic significance of LCR abnormalities.

Aims:

  • To identify the proportion of patients with monoclonal gammopathies that have abnormal serum LCR at presentation.

  • To identify how many patients have abnormal serum LCR but no other evidence of excess light chain production.

  • To establish the sensitivity of serum LCR for the presence of Bence Jones proteinuria.

Method and Setting: We analyzed data from a consecutive cohort of 496 patients with a newly identified paraprotein (by serum or urine protein electrophoresis and immunofixation), who had samples referred to the Immunology Department at Hull Royal Infirmary between 05/03/06 and 07/31/07. Serum FLC analysis was performed by a latex-enhanced immunoassay (The Binding Site, Birmingham, UK on a Beckman-Coulter IMMAGE nephelometric analyzer). Serum (SPE) and urine (UPE) protein electrophoresis were perfomed by SEBIA Hydrasys gel system or Capillarys 2 capillary electrophoresis system.

Results: Paraproteins were evident by SPE in 98% of patients (488 of 496). In the remaining 8 patients (2%) the paraprotein was only visible by UPE. Serum LCR was outside the standard reference interval (0.26–1.65) in 272 (55%) of all patients and in 124 (36%) of the 343 patients who had no FLC detected by SPE or UPE. Urines were received from 281 (57%) patients and a paraprotein was detected in 151 (54%) of these by UPE. FLC was detected in 126 (83%) of urines containing a paraprotein and in 89 (59%) was the sole paraprotein present in the urine. Of the 126 patients who had FLC detected by UPE, 124 (98%) had serum LCR outside the standard reference interval, and 119 (94%) had serum LCR outside the mean±3.5 sd range (0.18–2.01). The remaining two patients with normal LCR both had IgG-kappa paraproteins with a small free kappa band in the urine. The molecular weight of these free kappa bands has not yet been confirmed by SDS-PAGE electrophoresis and immunoblotting.

Conclusions:

  • Raised serum LCR was present in 55% of patients with a paraprotein at diagnosis.

  • 36% of patients with no other evidence of excess light chain production had abnormal LCR.

  • Using the LCR standard reference interval had a sensitivity of 98% for the presence of Bence Jones proteinuria.

This high sensitivity of LCR for Bence Jones proteinuria supports the cessation of UPE and its replacement with serum LCR. Our cohort of newly presenting, unselected patients with monoclonal gammopathies will be followed to determine the prognostic value of LCR for these patients.

Author notes

Disclosure:Consultancy: Russell Patmore is a current member of an advisory board of Roche Pharmaceuticals. Research Funding: The Binding Site has funded other research concerning the use of free light chain assays in our laboratory. They have also provided travel expenses to enable the presenting author to attend the 49th ASH Annual Meeting, 2007.