Polyclonal Free Light Chain Elevation and Mortality In the German Heinz Nixdorf Recall Study

Abstract 3903

Abnormalities of the κ:λ free light chain (FLC) ratio can detect monoclonal FLC elevations and are a valuable tool in the diagnosis and follow-up of plasma cell dyscrasias. However, due to their generation in active cells of the immune system and their renal metabolism, polyclonal FLC elevations might also provide valuable hints to other pathologic conditions. Recent reports suggest e.g. a role in predicting outcome in chronic viral infectious diseases. In a previous study, we screened the cohort of the German Heinz Nixdorf Recall Study for monoclonal gammopathies by combined serum protein electrophoresis and screening immunofixation (Eisele et al. EHA 2010, Abstract #0949) and also measured FLC concentration by nephelometric immunoassays (FREELITE, The Binding Site, UK) in all available samples. We here report our first preliminary results of the analysis of polyclonal FLC elevation with regard to all-cause mortality in the Heinz Nixdorf Recall cohort.

The Heinz Nixdorf Recall Study cohort comprises 4814 men and women from 3 large adjacent cities in Germany. Subjects were randomly selected from statutory lists of residence and gave informed consent. We screened serum samples from the baseline examination which took place from 2000 until 2003. After exclusion of samples with monoclonal FLC elevation, laboratory results together with clinical information of 4350 study subjects (2180 male, 2170 female) were available for analysis. We used summated FLC (total FLC, tFLC) as a measure for polyclonal elevation. tFLC ranged from 2.7 to 275 mg/l with a median of 30.2 mg/l. High levels of tFLC were associated with high-sensitive CRP (hsCRP) and chronic kidney disease (CKD). Both quintiles of tFLC and CKD stage were associated with shorter survival in univariate analysis. Using the median as cutoff, tFLC still separated groups with different survival within CKD stages 0 and 1. tFLC remained an independent predictor of survival in multivariable cox regression analysis adjusted for sex, age, hsCRP and CKD stage (HR 1.13 (95%CI 1.03 – 1.24 per quintile, p=0.0068). For the 274 deaths that occurred during a median observational time of 5 years we had information available from death certificates. Causes of death were categorized into cardiopulmonary, infectious, cancer, and other. The number of deaths increased from the lowest to the highest tFLC quintile (34 vs. 98), however we found no associations of tFLC with categorized causes of death.

Polyclonal FLC measurements are affected by a variety of health conditions and may thus be subject to fluctuations over time. We are currently measuring FLC in the 5-year follow-up samples of the Heinz Nixdorf Recall study. This will provide us with a more precise estimate of polyclonal FLC elevation and will help us to further define their role in predicting mortality. These results will also be reported at the conference.