Free light chains of immunoglobulins in serum as biomarker of activity in systemic lupus erythematosus

Authors: Hrnčíř Zb;  M. Drahošová 1;  T. Soukup;  J. Tomš
Authors‘ workplace: II. interní klinika a 1Ústav klinické imunologie a alergologie, Lékařská fakulta UK a Fakultní nemocnice, Hradec Králové
Published in: Čes. Revmatol., 21, 2013, No. 1, p. 4-10.
Category: Original Papers


The molecules of immunoglobulins (Ig) include two identical heavy and two identical light chains. More light than heavy chains of Ig are produced under physiological conditions, and so free light chains (FLC) may be detected in biological fluids, especially in serum. Systemic lupus erythematosus (SLE) in associated with polyclonal activation of B cells, and propotional elevation of FLC kappa and FLC lambda values in serum with normal relation of FLC kappa:FLC lambda should be expected in active form of SLE.

To explore the changes of serum concentration of FLC kappa and FLC lambda as putative biomarkers of SLE disease activity in a prospective, comparative, and cross-over study.

Eighty-three adult SLE (ACR/1982, update in 1997) patients and 33 age- and sex-matched healthy controls were enrolled; concomitant infection, monoclonal gammopathy and renal failure in patients under study were excluded. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K): a score ≥6 was considered clinically important. FLC kappa and FLC lambda in serum were analysed by quantitative nephelometric assay and compared against SLEDAI-2K and serological biomarkers IgG, C3, C4, „total“ ANA, anti-dsDNA, and antinucleosome Abs. Statistical analysis using Medcalc-Statistical software programme was made.

Serum concentration of FLC kappa, FLC lambda and total FLC kappa + FLC lambda in 22 SLE with SLEDAI-2K ≥6, and also in 61 SLE with SLEDAI-2K <6 was significantly higher against healthy controls (p = 0.003 - <0.001) except FLC lambda in SLE with SLEDAI-2K <6 against controls (p > 0.05). In SLE with SLEDAI-2K ≥6 the concentration of FLC kappa, FLC lambda and FLC kappa + FLC lambda was always significantly higher than in SLE with SLEDAI-2K <6 (p < 0.001). In total group of 83 SLE a significant correlation (p < 0.001) was found between SLEDAI-2K score and FLC kappa (r = 0.56), FLC lambda (r = 0.58) and FLC kappa + FLC lambda (r = 0.62). FLC analysis against serum values of Abs under study demonstrated a strong correlation namely between FLC kappa, FLC lambda and FLC kappa + FLC lambda,and antinucleosome Abs (r = 0.59, r = 0.53, and r = 0.59).

FLC (kappa, lambda and total) concentration in serum correlate strongly with disease activity in SLE and is significantly higher in patients with clinically important SLEDAI-2K ≥6; these results are suggesting that serum FLC may be used as biomarker of SLE disease activity.

Key words:
Free light chains of immunoglobulins, systemic lupus erythematosus, SLEDAI-2K scoring system, biomarkers of disease activity in serum


1. Illei GG, Tackey E, Lapteva L, Lipsky PE. Biomarkers in systemic lupus erythematosus. Arthritis Rheum 2004;50:2048–2061.

2. Ruperto N, Hanrahan LM, Alarcón GS, Belmont HM, Brey RL, Brunetta Pe, et al. International consensus for a definition of disease flare in lupus. Lupus 2011;20:453–462.

3. Romero-Diaz J, Isenberg D, Ramsey-Goldman R. Measures of adult systemic lupus erythematosus. Arthritis Care Res 2011;63 (S11):S37–S46.

4. Steiman AJ, Gladman DD, Ibanez D, Urowitz MB, et al. Outcomes in patients with systemic lupus erythematosus with and without a prolonged serologically active clinically quiescent period. Arthritis Care Res 2012;64:511–518.

5. Ho A, Magder LS, Barr SG, Petri M. Decrease in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus. Arthritis Rheum 2001;44:2342–2349.

6. Aggarwal R, Sequeira W, Kokebie R, Mikolaitis RA, Fogg L, Finnegan A, et al. Serum free light chains as biomarkers for systemic lupus erythematosus disease aktivity. Arthritis Care Res 2011;63:891–898.

7. Bradwell AR, Carr Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Hihgly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001;47:673–680.

8. Rahna, A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med 2008;358:929–939.

9. Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002;29:288–291.

10. Cooper A, Bluestone R. Free immunoglobulin light chains in connective tissue diseases. Ann Rheum Dis 1968;27:537–543.

11. Epstein WV, Tan M. Increase of L-chains proteins in the sera of patients with systemic lupus erythematosus and the synovial fluid of patients with peripheral arthritis. Arthritis Rheum 1966;9:713–716.

12. Hirohata S, Miyamoto T. Increased intrathecal immunoglobulin synthesis of both kappa and lambda types in patients with systemic lupus erythematosus and central nervous system involvment. J Rheumatol 1986;13:715–721.

13. 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;209:473:477.

14. Cohen PL, Eisenberg RA, Dermer GB. Unusual acidic light chains in murine SLE serum. Clin Exp Immunol 1984;55:509–515.

15. Gordon C. Assessing disease activity and outcome in systemic lupus erythematosus. In Hochberg MC, et al. „Rheumatology“, Mosby 3. Ed., 2003:1389–1393.

16. Chiche L, Cournac JM, Mancini J, Bardin N, Thomas G, Jean R, et al. Normalization of serum-free light chanis in patients ­with systemic lupus erythematosus upon rituximab treatment and correlation with biological disease activity. Clin Rheumatol 2011;30:695–689.

17. Komerlink TG, Tekstra J, Thurlings RM, Boumans MHJ, Vos K, Tak PP, et al. Decreace in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann Rheum Dis 2010;69:2137–2144.

18. Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 2012;64:797–808.

19. Hrnčíř Zb. Imunoglobulinové volné lehké řetězce u revmatických chorob. Rheumatologia 2012;26:57–62.

Dermatology & STDs Paediatric rheumatology Rheumatology
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account