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Determination of serum free light chains as a marker of systemic lupus flare

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A Correction to this article was published on 07 March 2022

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Abstract

Introduction

The aim of this study was to explore the usefulness of the determination of free light chains (FLC) in serum as a biomarker of flare in patients with systemic lupus erythematosus (SLE) and to analyze the differences in their discriminatory capacity with complement C3 and C4.

Methods

This was a prospective cohort study. The definition of flare was based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index. The discriminatory capacity of FLC and C3 and C4 levels was compared using receiver operating characteristic (ROC) curves and the area under the curve (AUC).

Results

Forty-six patients were enrolled. Patients with SLE flare showed significantly lower C3 (p = 0.025) and C4 levels (p = 0.028), as well as a higher concentration of lambda light chains (λ-LC) (p = 0.028) compared with the non-flare group. λ-LC, as opposed to kappa light chains and total light chains, demonstrated a discriminatory capacity for detecting the presence of SLE flare (AUC 0.781), with 100% sensitivity, 65% specificity, and 69.6% of patients correctly classified for a cutoff point of ≥ 19.5 mg/L. Complement C3 and C4 also showed a high discriminatory capacity for SLE flare (AUC 0.804 and 0.837, respectively). Comparing λ-LC, C3, and C4, the last one demonstrates better discriminatory capacity for SLE flare with the highest AUC (0.837; 95% CI 0.663–1.000).

Conclusions

λ-LC have good discriminatory capacity for SLE flare and could be useful as a biomarker of SLE exacerbation.

Key Points

• The usefulness of free light chains as a biomarker could be compared with complement.

• Lambda free light chains have good discriminatory capacity for SLE flare.

• Free light chains are a promising marker of SLE activity

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References

  1. Cozzani E, Drosera M, Gasparini G, Parodi A (2014) Serology of lupus erythematosus: correlation between immunopathological features and clinical aspects. Autoimmune Dis 2014:321359. https://doi.org/10.1155/2014/321359

    Article  PubMed  PubMed Central  Google Scholar 

  2. ter Borg EJ, Horst G, Hummel EJ et al (1990) Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study. Arthritis Rheum 33:634–643

    Article  PubMed  Google Scholar 

  3. Smeenk RJ, Aarden LA, Swaak TJ (1996) Laboratory tests as predictors of disease exacerbations in systemic lupus erythematosus: comment on the article by Esdaile et al. Arthritis Rheum 39:2083–2085

    Article  CAS  PubMed  Google Scholar 

  4. Ng KP, Manson JJ, Rahman A, Isenberg DA (2006) Association of antinucleosome antibodies with disease flare in serologically active clinically quiescent patients with systemic lupus erythematosus. Arthritis Rheum 55:900–904. https://doi.org/10.1002/art.22356

    Article  CAS  PubMed  Google Scholar 

  5. 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 63:891–898. https://doi.org/10.1002/acr.20446

    Article  CAS  Google Scholar 

  6. Kaplan B, Livneh A, Sela B-A (2011) Immunoglobulin free light chain dimers in human diseases. ScientificWorldJournal 11:726–735. https://doi.org/10.1100/tsw.2011.65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ye Y, Li S-L, Xie M, Jiang P, Liu KG, Li YJ (2013) Judging disease activity in rheumatoid arthritis by serum free kappa and lambda light chain levels. Kaohsiung J Med Sci 29:547–553. https://doi.org/10.1016/j.kjms.2013.01.013

    Article  PubMed  Google Scholar 

  8. Deng X, Crowson CS, Rajkumar SV, Dispenzieri A, Larson DR, Therneau TM, Matteson EL, Kyle RA, Katzmann JA, Gabriel SE, Davis JM 3rd (2015) Elevation of serum immunoglobulin free light chains during the preclinical period of rheumatoid arthritis. J Rheumatol 42:181–187. https://doi.org/10.3899/jrheum.140543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Brito-Zerón P, Retamozo S, Gandía M et al (2012) Monoclonal gammopathy related to Sjögren syndrome: a key marker of disease prognosis and outcomes. J Autoimmun 39:43–48. https://doi.org/10.1016/j.jaut.2012.01.010

    Article  PubMed  Google Scholar 

  10. Gottenberg J-E, 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 66:23–27. https://doi.org/10.1136/ard.2006.052159

    Article  CAS  PubMed  Google Scholar 

  11. Hanaoka M, Gono T, Kawaguchi Y et al (2013) Urinary free light chain is a potential biomarker for ISN/RPS class III/IV lupus nephritis. Rheumatol Oxf Engl 52:2149–2157. https://doi.org/10.1093/rheumatology/ket108

    Article  Google Scholar 

  12. Aggarwal R (2013) Urinary free light chains: a potential biomarker in lupus nephritis. Rheumatol Oxf Engl 52:2106–2107. https://doi.org/10.1093/rheumatology/ket286

    Article  CAS  Google Scholar 

  13. Tan EM, Cohen AS, Fries JF, Masi AT, McShane D, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Article  CAS  PubMed  Google Scholar 

  14. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725. https://doi.org/10.1002/art.1780400928 (199709)40:9<1725::AID-ART29>3.0.CO;2-Y

    Article  CAS  PubMed  Google Scholar 

  15. Petri M, Orbai A-M, Alarcón GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sánchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven R, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686. https://doi.org/10.1002/art.34473

    Article  PubMed  PubMed Central  Google Scholar 

  16. Calvo-Alén J, Silva-Fernández L, Úcar-Angulo E et al (2013) SER consensus statement on the use of biologic therapy for systemic lupus erythematosus. Reumatol Clin 9:281–296. https://doi.org/10.1016/j.reuma.2013.04.001

    Article  PubMed  Google Scholar 

  17. Castrejón I, Rúa-Figueroa I, Rosario MP, Carmona L (2014) Clinical composite measures of disease activity and damage used to evaluate patients with systemic lupus erythematosus: a systematic literature review. Reumatol Clin 10:309–320. https://doi.org/10.1016/j.reuma.2014.01.012

    Article  PubMed  Google Scholar 

  18. Mikdashi J, Nived O (2015) Measuring disease activity in adults with systemic lupus erythematosus: the challenges of administrative burden and responsiveness to patient concerns in clinical research. Arthritis Res Ther 17:183. https://doi.org/10.1186/s13075-015-0702-6

    Article  PubMed  PubMed Central  Google Scholar 

  19. Napodano C, Pocino K, Rigante D et al (2019) Free light chains and autoimmunity. Autoimmun Rev 18:484–492. https://doi.org/10.1016/j.autrev.2019.03.003

    Article  CAS  PubMed  Google Scholar 

  20. Hopper JE, Sequeira W, Martellotto J, Papagiannes E, Perna L, Skosey JL (1989) Clinical relapse in systemic lupus erythematosus: correlation with antecedent elevation of urinary free light-chain immunoglobulin. J Clin Immunol 9:338–350

    Article  CAS  PubMed  Google Scholar 

  21. Hopper JE, Papagiannes E (1986) Evidence by radioimmunoassay that mitogen-activated human blood mononuclear cells secrete significant amounts of light chain Ig unassociated with heavy chain. Cell Immunol 101:122–131

    Article  CAS  PubMed  Google Scholar 

  22. Jolly M, Francis S, Aggarwal R et al (2014) Serum free light chains, interferon-alpha, and interleukins in systemic lupus erythematosus. Lupus 23:881–888. https://doi.org/10.1177/0961203314530793

    Article  CAS  PubMed  Google Scholar 

  23. Żychowska I, Suszek D, Dryglewska M et al (1960) (2018) [Serum free light chains for monitoring systemic lupus erythematosus activity]. Wiadomosci Lek Wars Pol 71:21–31

    Google Scholar 

  24. 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:e0138753. https://doi.org/10.1371/journal.pone.0138753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sakane T, Suzuki N, Takada S et al (1988) B cell hyperactivity and its relation to distinct clinical features and the degree of disease activity in patients with systemic lupus erythematosus. Arthritis Rheum 31:80–87

    Article  CAS  PubMed  Google Scholar 

  26. Kao AH, Navratil JS, Ruffing MJ et al (2010) Erythrocyte C3d and C4d for monitoring disease activity in systemic lupus erythematosus. Arthritis Rheum 62:837–844. https://doi.org/10.1002/art.27267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors want to thank the Spanish Society of Rheumatology for the help in the translation of the manuscript.

Funding

This work is supported by a grant from Madrid Society of Rheumatology.

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Authors and Affiliations

  1. Division of Rheumatology, Hospital Universitario Severo Ochoa, Avda. de Orellana s/n CP 28911, Leganés, Madrid, Spain

    Ana Belén Rodríguez-Cambrón, Francis Rey Pazos, Cristina Macía-Villa, María Alcalde-Villar, Paz Collado-Ramos, Félix Manuel Cabero Del Pozo, Eva Álvarez-Andrés & Ana Cruz-Valenciano

  2. Division of Biochemistry, Hospital Universitario Severo Ochoa, Madrid, Spain

    Juana Jiménez-Jiménez

  3. Division of Rheumatology, Hospital Universitario Ramón y Cajal, Madrid, Spain

    María Ángeles Blázquez-Cañamero

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  1. Ana Belén Rodríguez-Cambrón
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Correspondence to Ana Belén Rodríguez-Cambrón.

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The original online version of this article was revised: In the original version of this article, the given and family names of authors were incorrectly structured. These has been corrected.

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Rodríguez-Cambrón, A.B., Jiménez-Jiménez, J., Blázquez-Cañamero, M.Á. et al. Determination of serum free light chains as a marker of systemic lupus flare. Clin Rheumatol 39, 449–454 (2020). https://doi.org/10.1007/s10067-019-04827-4

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