The impact of exercise on the variation of serum free light chains

Measurement of serum free light chains (sFLC) has become an established method for screening, prognostic evaluation, and monitoring of multiple myeloma and related monoclonal gammopathies [1]. In recent years it was shown that non-clonal elevations of sFLC, measured as the κand λFLC sum (ΣFLC), can act as a global marker of immune stimulation, and may be linked to severity of immune disease [2]. In a cohort of 15,859 individuals all aged above 50 years, Dispenzieri et al. found that ΣFLC is a significant predictor of worse overall survival in persons without plasma cell disorders [3]. sFLC as such is regarded a biomarker of frailty in the elderly. Due to the well-defined clinical role of sFLC, the longterm biological variation of monoclonal FLC in patients with monoclonal gammopathies [4] and polyclonal FLC in healthy controls were recently assessed [5]. Immune status is not solely influenced by pathogen exposure or inherent immune disorders, other factors such as exercise also play a role. Acute exercise, e.g., induces immune stimulation, which is reflected by transiently increased concentrations of sensitive inflammation markers [6]. Whether or not exercise can affect FLC concentrations has to our knowledge not been assessed before. In the present study, we hypothesized that exerciseinduced immune stimulation may affect sFLC concentrations. To test this hypothesis we monitored sFLC concentrations in 37 elderly volunteers who participated in the Nijmegen Four Days Marches and walked 30 km at 4 consecutive days at a self-selected pace. Thirty-seven elderly men and women (age 76–86 years) of the 2013 Nijmegen Four Days Marches (an annual walking event in The Netherlands) volunteered to participate in our study. The experimental set-up to determine the demographic characteristics of the volunteers, their health status and exercise characteristics are described previously [7]. Baseline blood measurements were performed 12–36 h preceding the start. Immediately after finishing on the fourth day, all baseline measurements were repeated. FLC measurements were measured in batches of frozen and anonymized sera. Sera aliquots were stored at –20 °C directly after collection and thawed directly before analysis. Serum FLC analysis was performed on the SPAplus instrument using Freelite reagents (The Binding Site Ltd, Birmingham, UK). ΣFLC was calculated as the sum of the individual measurements of both κFLC and λFLC. Values are presented as means ± standard deviation. *Corresponding author: Joannes F.M. Jacobs, PhD, MD, Radboud University Medical Center, Department of Laboratory Medicine, Laboratory Medical Immunology (route 469), Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands, Phone: +31 24 3617414, Fax: +31 24 3619415, E-mail: H.Jacobs@Radboudumc.nl; and Department of Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands; and Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands Thijs M.H. Eijsvogels: Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands; and Henry Low Heart Center, Department of Cardiology, Hartford Hospital, Hartford, CT, USA Kornelis S.M. van der Geest and Annemieke M.H. Boots: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands; and Groningen Research initiative on healthy Ageing and Immune Longevity (GRAIL), Groningen, The Netherlands Hans J.P.M. Koenen and Irma Joosten: Department of Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands Colin A. Hutchison: Renal Institute of Birmingham, University Hospital Birmingham, Birmingham, UK; and Hawke’s Bay District Health Board, Hawke’s Bay, New Zealand Maria T.E. Hopman: Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands