Skip to main content
Top
Published in: Clinical Rheumatology 12/2016

01-12-2016 | Original Article

The significance and predictive value of free light chains in the urine of patients with chronic inflammatory rheumatic disease

Authors: Carsten Paul Bramlage, Britta Froelich, Manuel Wallbach, Joan Minguet, Clemens Grupp, Cornelia Deutsch, Peter Bramlage, Michael Koziolek, Gerhard Anton Müller

Published in: Clinical Rheumatology | Issue 12/2016

Login to get access

Abstract

In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p < 0.001; λ, r = 0.398, p < 0.001) and erythrocyte sedimentation rate (κ, r = 0.692, p < 0.001; λ, r = 0.612, p < 0.001). Patients being treated with rituximab displayed FLC levels similar to those of the reference group. There were clear elevations in both κ and λ FLCs in patients with rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.
Literature
1.
go back to reference Aggarwal R (2013) Urinary free light chains: a potential biomarker in lupus nephritis. Rheumatology (Oxford) 52:2106–2107CrossRef Aggarwal R (2013) Urinary free light chains: a potential biomarker in lupus nephritis. Rheumatology (Oxford) 52:2106–2107CrossRef
2.
go back to reference Aggarwal R, Sequeira W, Kokebie R, Mikolaitis RA, Fogg L, Finnegan A, Plaas A, Block JA, Jolly M (2011) Serum free light chains as biomarkers for systemic lupus erythematosus disease activity. Arthritis Care Res (Hoboken) 63:891–898CrossRef Aggarwal R, Sequeira W, Kokebie R, Mikolaitis RA, Fogg L, Finnegan A, Plaas A, Block JA, Jolly M (2011) Serum free light chains as biomarkers for systemic lupus erythematosus disease activity. Arthritis Care Res (Hoboken) 63:891–898CrossRef
3.
go back to reference Bradwell AR (2005) Serum free light chain measurements move to center stage. Clin Chem 51:805–807CrossRefPubMed Bradwell AR (2005) Serum free light chain measurements move to center stage. Clin Chem 51:805–807CrossRefPubMed
5.
go back to reference Brouwer J, Otting-van de Ruit M, Busking-van der Lely H (1985) Estimation of free light chains of immunoglobulins by enzyme immunoassay. Clin Chim Acta 150:267–274CrossRefPubMed Brouwer J, Otting-van de Ruit M, Busking-van der Lely H (1985) Estimation of free light chains of immunoglobulins by enzyme immunoassay. Clin Chim Acta 150:267–274CrossRefPubMed
6.
go back to reference Carubbi F, Alunno A, Cipriani P, Bartoloni E, Ciccia F, Triolo G, Gerli R, Giacomelli R (2014) Rituximab in primary Sjogren’s syndrome: a ten-year journey. Lupus 23:1337–1349CrossRefPubMed Carubbi F, Alunno A, Cipriani P, Bartoloni E, Ciccia F, Triolo G, Gerli R, Giacomelli R (2014) Rituximab in primary Sjogren’s syndrome: a ten-year journey. Lupus 23:1337–1349CrossRefPubMed
7.
go back to reference Chiche L, Cournac JM, Mancini J, Bardin N, Thomas G, Jean R, Schleinitz N, Kaplanski G, Durand JM, Boucraut J, Harle JR (2011) Normalization of serum-free light chains in patients with systemic lupus erythematosus upon rituximab treatment and correlation with biological disease activity. Clin Rheumatol 30:685–689CrossRefPubMed Chiche L, Cournac JM, Mancini J, Bardin N, Thomas G, Jean R, Schleinitz N, Kaplanski G, Durand JM, Boucraut J, Harle JR (2011) Normalization of serum-free light chains in patients with systemic lupus erythematosus upon rituximab treatment and correlation with biological disease activity. Clin Rheumatol 30:685–689CrossRefPubMed
8.
go back to reference Draborg AH, Lydolph MC, Westergaard M, Olesen Larsen S, Nielsen CT, Duus K, Jacobsen S, Houen G (2015) 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 10:e0138753CrossRefPubMedPubMedCentral Draborg AH, Lydolph MC, Westergaard M, Olesen Larsen S, Nielsen CT, Duus K, Jacobsen S, Houen G (2015) 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 10:e0138753CrossRefPubMedPubMedCentral
9.
go back to reference Gottenberg JE, Aucouturier F, Goetz J, Sordet C, Jahn I, Busson M, Cayuela JM, Sibilia J, Mariette X (2007) Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogren’s syndrome. Ann Rheum Dis 66:23–27CrossRefPubMed Gottenberg JE, Aucouturier F, Goetz J, Sordet C, Jahn I, Busson M, Cayuela JM, Sibilia J, Mariette X (2007) Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogren’s syndrome. Ann Rheum Dis 66:23–27CrossRefPubMed
10.
go back to reference Gottenberg JE, Miceli-Richard C, Ducot B, Goupille P, Combe B, Mariette X (2009) Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort. Arthritis Res Ther 11:R114CrossRefPubMedPubMedCentral Gottenberg JE, Miceli-Richard C, Ducot B, Goupille P, Combe B, Mariette X (2009) Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort. Arthritis Res Ther 11:R114CrossRefPubMedPubMedCentral
11.
go back to reference Hanaoka M, Gono T, Kawaguchi Y, Uchida K, Koseki Y, Katsumata Y, Kaneko H, Takagi K, Ichida H, Nitta K, Yamanaka H (2013) Urinary free light chain is a potential biomarker for ISN/RPS class III/IV lupus nephritis. Rheumatology (Oxford) 52:2149–2157CrossRef Hanaoka M, Gono T, Kawaguchi Y, Uchida K, Koseki Y, Katsumata Y, Kaneko H, Takagi K, Ichida H, Nitta K, Yamanaka H (2013) Urinary free light chain is a potential biomarker for ISN/RPS class III/IV lupus nephritis. Rheumatology (Oxford) 52:2149–2157CrossRef
12.
go back to reference Hopper JE, Golbus J, Meyer C, Ferrer GA (2000) Urine free light chains in SLE: clonal markers of B-cell activity and potential link to in vivo secreted Ig. J Clin Immunol 20:123–137CrossRefPubMed Hopper JE, Golbus J, Meyer C, Ferrer GA (2000) Urine free light chains in SLE: clonal markers of B-cell activity and potential link to in vivo secreted Ig. J Clin Immunol 20:123–137CrossRefPubMed
13.
go back to reference Hutchison CA, Harding S, Hewins P, Mead GP, Townsend J, Bradwell AR, Cockwell P (2008) Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol 3:1684–1690CrossRefPubMedPubMedCentral Hutchison CA, Harding S, Hewins P, Mead GP, Townsend J, Bradwell AR, Cockwell P (2008) Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol 3:1684–1690CrossRefPubMedPubMedCentral
14.
go back to reference Hutchison CA, Landgren O (2011) Polyclonal immunoglobulin free light chains as a potential biomarker of immune stimulation and inflammation. Clin Chem 57:1387–1389CrossRefPubMed Hutchison CA, Landgren O (2011) Polyclonal immunoglobulin free light chains as a potential biomarker of immune stimulation and inflammation. Clin Chem 57:1387–1389CrossRefPubMed
15.
go back to reference Jolly M, Francis S, Aggarwal R, Mikolaitis RA, Niewold TB, Chubinskaya S, Block JA, Scanzello C, Sequeira W (2014) Serum free light chains, interferon-alpha, and interleukins in systemic lupus erythematosus. Lupus 23:881–888CrossRefPubMed Jolly M, Francis S, Aggarwal R, Mikolaitis RA, Niewold TB, Chubinskaya S, Block JA, Scanzello C, Sequeira W (2014) Serum free light chains, interferon-alpha, and interleukins in systemic lupus erythematosus. Lupus 23:881–888CrossRefPubMed
16.
go back to reference Jones RB (2014) Rituximab in the treatment of anti-neutrophil cytoplasm antibody-associated vasculitis. Nephron Clin Pract 128:243–249CrossRefPubMed Jones RB (2014) Rituximab in the treatment of anti-neutrophil cytoplasm antibody-associated vasculitis. Nephron Clin Pract 128:243–249CrossRefPubMed
17.
go back to reference Kormelink TG, Tekstra J, Thurlings RM, Boumans MH, Vos K, Tak PP, Bijlsma JW, Lafeber FP, Redegeld FA, van Roon JA (2010) Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann Rheum Dis 69:2137–2144CrossRefPubMed Kormelink TG, Tekstra J, Thurlings RM, Boumans MH, Vos K, Tak PP, Bijlsma JW, Lafeber FP, Redegeld FA, van Roon JA (2010) Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann Rheum Dis 69:2137–2144CrossRefPubMed
18.
go back to reference Lopez-Olivo MA, Amezaga Urruela M, McGahan L, Pollono EN, Suarez-Almazor ME (2015) Rituximab for rheumatoid arthritis. Cochrane Database Syst Rev 1:Cd007356PubMed Lopez-Olivo MA, Amezaga Urruela M, McGahan L, Pollono EN, Suarez-Almazor ME (2015) Rituximab for rheumatoid arthritis. Cochrane Database Syst Rev 1:Cd007356PubMed
19.
go back to reference Nakano T, Nagata A, Takahashi H (2004) Ratio of urinary free immunoglobulin light chain kappa to lambda in the diagnosis of Bence Jones proteinuria. Clin Chem Lab Med 42:429–434CrossRefPubMed Nakano T, Nagata A, Takahashi H (2004) Ratio of urinary free immunoglobulin light chain kappa to lambda in the diagnosis of Bence Jones proteinuria. Clin Chem Lab Med 42:429–434CrossRefPubMed
20.
go back to reference Segal R, Yaron M, Tartakovsky B (1990) Methotrexate: mechanism of action in rheumatoid arthritis. Semin Arthritis Rheum 20:190–200CrossRefPubMed Segal R, Yaron M, Tartakovsky B (1990) Methotrexate: mechanism of action in rheumatoid arthritis. Semin Arthritis Rheum 20:190–200CrossRefPubMed
22.
go back to reference Stokes MB, Valeri AM, Herlitz L, Khan AM, Siegel DS, Markowitz GS, D’Agati VD (2015) Light chain proximal tubulopathy: clinical and pathologic characteristics in the modern treatment era. J Am Soc Nephrol Stokes MB, Valeri AM, Herlitz L, Khan AM, Siegel DS, Markowitz GS, D’Agati VD (2015) Light chain proximal tubulopathy: clinical and pathologic characteristics in the modern treatment era. J Am Soc Nephrol
23.
go back to reference van Gestel AM, Prevoo ML, van ‘t Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL (1996) Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum 39:34–40CrossRefPubMed van Gestel AM, Prevoo ML, van ‘t Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL (1996) Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum 39:34–40CrossRefPubMed
24.
go back to reference Waldmann TA, Strober W, Mogielnicki RP (1972) The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J Clin Invest 51:2162–2174CrossRefPubMedPubMedCentral Waldmann TA, Strober W, Mogielnicki RP (1972) The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J Clin Invest 51:2162–2174CrossRefPubMedPubMedCentral
25.
go back to reference Zhang R, Li M, Chouhan KK, Simon EE, Hamm LL, Batuman V (2013) Urine free light chains as a novel biomarker of acute kidney allograft injury. Clin Transpl 27:953–960CrossRef Zhang R, Li M, Chouhan KK, Simon EE, Hamm LL, Batuman V (2013) Urine free light chains as a novel biomarker of acute kidney allograft injury. Clin Transpl 27:953–960CrossRef
Metadata
Title
The significance and predictive value of free light chains in the urine of patients with chronic inflammatory rheumatic disease
Authors
Carsten Paul Bramlage
Britta Froelich
Manuel Wallbach
Joan Minguet
Clemens Grupp
Cornelia Deutsch
Peter Bramlage
Michael Koziolek
Gerhard Anton Müller
Publication date
01-12-2016
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 12/2016
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-016-3437-0

Other articles of this Issue 12/2016

Clinical Rheumatology 12/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.