Elevated serum free light chains predict cardiovascular risk in type 1 diabetes mellitus

Authors

  • Lauren Marie Quinn The Medical School, University of Birmingham, Birmingham, UK
  • Sheridan Mcwilliam
  • John P Campbell Clinical Immunology Service, The Medical School, University of Birmingham, Birmingham, UK
  • Yan Wang Clinical Immunology Service, The Medical School, University of Birmingham, Birmingham, UK
  • David Hughes Clinical and Experimental Medicine, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, UK
  • Mark T Drayson Clinical Immunology Service, The Medical School, University of Birmingham, Birmingham, UK
  • Parth Narendran Clinical and Experimental Medicine, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, UK

DOI:

https://doi.org/10.15277/bjd.2016.107

Keywords:

free light chains, cardiovascular disease, type 1 diabetes mellitus

Abstract

Aims: Increased serum polyclonal combined immunoglobulin free light chain (cFLC = FLCκ+FLCλ) has been shown to predict cardiovascular (CV) events in South Asians with type 2 diabetes mellitus. We examined whether cFLC also predicted CV risk in unselected patients with type 1 diabetes mellitus.

Methods: cFLC was estimated in the serum of 55 adults with type 1 diabetes mellitus. CV risk was measured through two validated risk engines: Q-Risk and PROCAM. Statistical association was tested using the parametic Pearson’s or the Spearman’s rank correlation coefficient test, Student t-test or Mann-Whitney U-test and Kruskall-Wallis test for parametric or non-parametrically distributed data accordingly.

Results: cFLC was associated with CV risk. This association was significant when estimated through either risk engine (PROCAM p=0.003, Q-Risk p=0.012). cFLC was associated with diabetes mellitus duration (p=0.003), age (p=0.006) and history of cardiac disease (p=0.042).

Conclusions: These findings indicate that cFLC is a marker of CV risk in people with type 1 diabetes mellitus. Moreover, it supports emerging data demonstrating cFLC as a prognostic indicator for mortality.

References

van der Heijden M, Kraneveld A, Redegeld F. Free immunoglobulin light chains as target in the treatment of chronic inflammatory diseases. Eur J Pharmacol 2006;533:319-26. https://doi.org/10.1016/j.ejphar.2005.12.065

Hutchison CA, Harding S, Hewins P, 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. http://dx.doi.org/10.2215/CJN.02290508

Sølling K, Sølling J, Rømer FK. Free light chains of immunoglobulins in serum from patients with rheumatoid arthritis, sarcoidosis, chronic infections and pulmonary cancer. Acta Med Scand 1981;209:473-7. https://doi.org/10.1111/j.0954-6820.1981.tb11632.x

Draborg AH, Lydolph MC, Westergaard M, et al. Elevated concentrations of serum immunoglobulin free light chains in systemic lupus erythematosus patients in relation to disease activity, inflammatory status, B cell activity and Epstein-Barr virus antibodies. PLoS One 2015;10:e0138753. http://dx.doi.org/10.1371/journal.pone.0138753

Festa A, D’Agostino R, Howard G, Mykkänen L, Tracy RP, Haffner SM. Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study. Kidney Int 2002;58:1703-10. https://doi.org/10.1046/j.1523-1755.2000.00331.x

Hutchinson AT, Jones DR, Raison RL. The ability to interact with cell membranes suggests possible biological roles for free light chain. Immunol Lett 2012;142:75-7. http:dx.doi.org/10.1016/j.imlet.2011.10.013

Dispenzieri A, Katzmann JA, Kyle RA, 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. http://dx.doi.org/10.1016/j.mayocp.2012.03.009

Anandram S, Assi LK, Lovatt T, et al. Elevated, combined serum free light chain levels and increased mortality: a 5-year follow-up, UK study. J Clin Pathol 2012;65:1036-42. http://dx.doi.org/10.1136/jclinpath-2012-200910

Bellary S, Faint JM, Assi LK, et al. Elevated serum free light chains predict cardiovascular events in type 2 diabetes. Diabetes Care 2014;37:2028-30. http:dx.doi.org/10.2337/dc13-2227

University of Birmingham. Chronic Disease Research into Diabetes Study. 2015. Available from: http://www.birmingham.ac.uk/research/activity/mds/trials/pccrtu/trials/cdr/index.aspx (accessed 21 Jan 2015).

Campbell JP, Cobbold M, Wang Y, 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. http://dx.doi.org/10.1016/j.jim.2013.01.014

Hopper JE, Papagiannes E. Evidence by radioimmunoassay that mitogen-activated human blood mononuclear cells secrete significant amounts of light chain Ig unassociated with heavy chain. Cell Immunol 1986;101:122-31. https://doi.org/10.1016/0008-8749(86)90191-7

Corcos D, Osborn MJ, Matheson LS, et al. Immunoglobulin aggregation leading to Russell body formation is prevented by the antibody light chain. Blood 2010;115:282-8. http://dx.doi.org/10.1182/blood-2009-07-234864

Katzmann JA, Clark RJ, Abraham RS, 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.

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Published

2016-12-20

Issue

Vol. 16 No. 4 (2016)

Section

Original Research

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