Abstract
Background: Immunoglobulin κ and λ free light chains (FLC) are important serum biomarkers for diagnosing and monitoring plasma cell dyscrasias (via the κ:λ FLC ratio), and assessing immune competence and activation status (via ∑FLC). FLCs are produced, in excess of heavy chains, from healthy plasma cells during immunoglobulin production, but unlike intact immunoglobulins that are cleared by cellular catabolism over a number of weeks, FLC are rapidly cleared from the bloodstream by the renal glomerulus with a half-life of 3 (κ FLC)–6 (λ FLC) hours. Marathon running has been shown to acutely and transiently decrease renal function, however, the impact of prolonged aerobic exercise on FLC levels remains unknown.
Methods: We measured serum FLC levels in 60 runners before, and immediately after, the 2010 Eindhoven Marathon.
Results: A significant increase (p<0.01) in κ FLC levels was observed after the marathon, and κ FLC correlated positively with serum creatinine levels. No changes were observed for λ FLC, and thus, there were subtle elevations in the ∑FLC and FLC ratio in some participants. Indeed, we found that 13% of participants had an abnormally increased FLC ratio upon completion of the marathon; a phenomenon previously observed in renal diseases.
Conclusions: Abnormal FLC ratios observed after exercise reflected an increase in serum κ FLC levels, which may be due to acute and transient reductions in renal function during exercise, though we also observed an increase in serum IgG and IgA and thus cannot exclude exercise-induced immune stimulation or immunoglobulin redistribution.
References
1. Bradwell AR. Serum free light chain analysis (plus hevylite), 6th ed. Birmingham: Binding Site Group, 2010.Search in Google Scholar
2. Deng X, Crowson CS, Rajkumar SV, Dispenzieri A, Larson DR, Therneau TM, et al. Elevation of serum immunoglobulin free light chains during the preclinical period of rheumatoid arthritis. J Rheumatol 2015;42:181–7.10.3899/jrheum.140543Search in Google Scholar PubMed PubMed Central
3. Bellary S, Faint JM, Assi LK, Hutchison CA, Harding SJ, Raymond NT, et al. Elevated serum free light chains predict cardiovascular events in type 2 diabetes. Diabetes Care 2014;37:2028–30.10.2337/dc13-2227Search in Google Scholar PubMed
4. Hutchison CA, Burmeister A, Harding SJ, Basnayake K, Church H, Jesky MD, et al. Serum polyclonal immunoglobulin free light chain levels predict mortality in people with chronic kidney disease. Mayo Clin Proc 2014;89:615–22.10.1016/j.mayocp.2014.01.028Search in Google Scholar PubMed
5. Drayson MT. Using single protein biomarkers to predict health and disease in diverse patient populations: a new role for assessment of immunoglobulin free light chains. Mayo Clin Proc 2012;87:505–7.10.1016/j.mayocp.2012.04.004Search in Google Scholar PubMed PubMed Central
6. Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Therneau TM, Colby CL, et al. Use of nonclonal serum immunoglobulin free light chains to predict overall survival in the general population. Mayo Clin Proc 2012;87:517–23.10.1016/j.mayocp.2012.03.009Search in Google Scholar PubMed PubMed Central
7. Hutchison CA, Harding S, Hewins P, Mead GP, Townsend J, Bradwell AR, et al. Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol 2008;3:1684–90.10.2215/CJN.02290508Search in Google Scholar PubMed PubMed Central
8. McCullough PA, Chinnaiyan KM, Gallagher MJ, Colar JM, Geddes T, Gold JM, et al. Changes in renal markers and acute kidney injury after marathon running. Nephrology (Carlton) 2011;16:194–9.10.1111/j.1440-1797.2010.01354.xSearch in Google Scholar PubMed
9. Jacobs JF, Eijsvogels TM, van der Geest KS, Koenen HJ, Hutchison CA, Boots AM, et al. The impact of exercise on the variation of serum free light chains. Clin Chem Lab Med 2014;52:e239–42.10.1515/cclm-2014-0352Search in Google Scholar PubMed
10. Eijsvogels TM, Hoogerwerf MD, Maessen MF, Seeger JP, George KP, Hopman MT, et al. Predictors of cardiac troponin release after a marathon. J Sci Med Sport 2015;18:88–92.10.1016/j.jsams.2013.12.002Search in Google Scholar PubMed
11. Campbell JP, Cobbold M, Wang Y, Goodall M, Bonney SL, Chamba A, et al. Development of a highly-sensitive multi-plex assay using monoclonal antibodies for the simultaneous measurement of kappa and lambda immunoglobulin free light chains in serum and urine. J Immunol Methods 2013;391:1–13.10.1016/j.jim.2013.01.014Search in Google Scholar PubMed
12. Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol 2001;37:153–6.10.1016/S0735-1097(00)01054-8Search in Google Scholar
13. Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol 1974;37:247–8.10.1152/jappl.1974.37.2.247Search in Google Scholar PubMed
14. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.10.1186/cc5713Search in Google Scholar PubMed PubMed Central
15. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002;48:1437–44.10.1093/clinchem/48.9.1437Search in Google Scholar
16. Long JE, Ring C, Drayson M, Bosch J, Campbell JP, Bhabra J, et al. Vaccination response following aerobic exercise: can a brisk walk enhance antibody response to pneumococcal and influenza vaccinations? Brain Behav Immun 2012;26:680–7.10.1016/j.bbi.2012.02.004Search in Google Scholar PubMed
17. Jacobs JF, Hoedemakers RM, Teunissen E, Te Velthuis H. N Latex FLC serum free light-chain assays in patients with renal impairment. Clin Chem Lab Med 2014;52:853–9.10.1515/cclm-2013-0864Search in Google Scholar PubMed
18. Campbell JP, Stride AE, Cobbold M, Wang Y, Goodall M, Bonney SL, et al. Rapid test to identity myeloma kidney by measurement of serum free light chains. Clin Lymphoma Myeloma Leuk 2013;13:454.Search in Google Scholar
19. Walsh NP, Gleeson M, Shephard RJ, Woods JA, Bishop NC, Fleshner M, et al. Position statement. Part one: immune function and exercise. Exerc Immunol Rev 2011;17:6–63.Search in Google Scholar
20. Kosmadakis GC, Bevington A, Smith AC, Clapp EL, Viana JL, Bishop NC, et al. Physical exercise in patients with severe kidney disease. Nephron Clin Pract 2010;115:c7–16.10.1159/000286344Search in Google Scholar PubMed
21. Kosmadakis GC, John SG, Clapp EL, Viana JL, Smith AC, Bishop NC, et al. Benefits of regular walking exercise in advanced pre-dialysis chronic kidney disease. Nephrol Dial Transplant 2012;27:997–1004.10.1093/ndt/gfr364Search in Google Scholar PubMed
22. Dungey M, Hull KL, Smith AC, Burton JO, Bishop NC. Inflammatory factors and exercise in chronic kidney disease. Int J Endocrinol 2013;2013:569831.10.1155/2013/569831Search in Google Scholar PubMed PubMed Central
©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Editorial
- The way of prostate cancer diagnostics
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- Statistical methods used in the calculation of geriatric reference intervals: a systematic review
- Opinion Paper
- The side effects of translational omics: overtesting, overdiagnosis, overtreatment
- Genetics and Molecular Diagnostics
- Rapid detection of non-deletional mutations causing α-thalassemia by multicolor melting curve analysis
- General Clinical Chemistry and Laboratory Medicine
- Patient pools and the use of “patient means” are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay
- Long-term stability of glucose: 96-h study using Terumo Glycaemia tubes
- Glucose is stable during prolonged storage in un-centrifuged Greiner tubes with liquid citrate buffer, but not in serum and NaF/KOx tubes
- Croatian laboratories have a good knowledge of the proper detection and management of hemolyzed, icteric and lipemic samples
- Fetal exposure to ethanol: relationship between ethyl glucuronide in maternal hair during pregnancy and ethyl glucuronide in neonatal meconium
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- Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study
- Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients – a retrospective study
- Reference Values and Biological Variations
- Assessment of serum free light chain levels in healthy adults immediately after marathon running
- Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients
- Cancer Diagnostics
- An epidemiology-based model as a tool to monitor the outbreak of inappropriateness in tumor marker requests: a national scale study
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- Infectious Diseases
- Comparative evaluation of the Aptima HIV-1 Quant Dx assay and COBAS TaqMan HIV-1 v2.0 assay using the Roche High Pure System for the quantification of HIV-1 RNA in plasma
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- Diabetes
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- Letters to the Editors
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- More on the accuracy of the Architect enzymatic assay for hemoglobin A1c and its traceability to the IFCC reference system
- Assessing quality from an accuracy-based HbA1c proficiency survey
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- Between analyser differences in chloride measurements and thus anion gap cause different interpretations of the acid-base balance
- Non-albumininuric proteinuria: a urinary tubular marker in the diagnosis of diabetic kidney disease
- International Normalized Ratio (INR) testing: analytical and clinical performance of four point-of-care devices versus central laboratory instrumentation analysis
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Articles in the same Issue
- Frontmatter
- Editorial
- The way of prostate cancer diagnostics
- Review
- Statistical methods used in the calculation of geriatric reference intervals: a systematic review
- Opinion Paper
- The side effects of translational omics: overtesting, overdiagnosis, overtreatment
- Genetics and Molecular Diagnostics
- Rapid detection of non-deletional mutations causing α-thalassemia by multicolor melting curve analysis
- General Clinical Chemistry and Laboratory Medicine
- Patient pools and the use of “patient means” are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay
- Long-term stability of glucose: 96-h study using Terumo Glycaemia tubes
- Glucose is stable during prolonged storage in un-centrifuged Greiner tubes with liquid citrate buffer, but not in serum and NaF/KOx tubes
- Croatian laboratories have a good knowledge of the proper detection and management of hemolyzed, icteric and lipemic samples
- Fetal exposure to ethanol: relationship between ethyl glucuronide in maternal hair during pregnancy and ethyl glucuronide in neonatal meconium
- Comparing the effect of isotopically labeled or structural analog internal standards on the performance of a LC-MS/MS method to determine ciclosporin A, everolimus, sirolimus and tacrolimus in whole blood
- Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study
- Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients – a retrospective study
- Reference Values and Biological Variations
- Assessment of serum free light chain levels in healthy adults immediately after marathon running
- Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients
- Cancer Diagnostics
- An epidemiology-based model as a tool to monitor the outbreak of inappropriateness in tumor marker requests: a national scale study
- Comparative analysis of prostate cancer specific biomarkers PCA3 and ERG in whole urine, urinary sediments and exosomes
- Infectious Diseases
- Comparative evaluation of the Aptima HIV-1 Quant Dx assay and COBAS TaqMan HIV-1 v2.0 assay using the Roche High Pure System for the quantification of HIV-1 RNA in plasma
- Evaluating the use of procalcitonin in an asymptomatic, HIV-infected antiretroviral therapy-naïve, South African cohort
- Diabetes
- Early prediction of gestational diabetes: a practical model combining clinical and biochemical markers
- Letters to the Editors
- Highly-trained dogs’ olfactory system for detecting biochemical recurrence following radical prostatectomy
- More on the accuracy of the Architect enzymatic assay for hemoglobin A1c and its traceability to the IFCC reference system
- Assessing quality from an accuracy-based HbA1c proficiency survey
- HbG-Honolulu interferes with some cation-exchange HPLC HbA1c assays
- Between analyser differences in chloride measurements and thus anion gap cause different interpretations of the acid-base balance
- Non-albumininuric proteinuria: a urinary tubular marker in the diagnosis of diabetic kidney disease
- International Normalized Ratio (INR) testing: analytical and clinical performance of four point-of-care devices versus central laboratory instrumentation analysis
- Genetic screening of the makorin ring finger 3 gene in girls with idiopathic central precocious puberty
- Practical approach for medical validation of therapeutic drug monitoring results
- Marked elevation of procalcitonin in a patient with a drug related infusion reaction to rituximab