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Plasma C4d as marker for lupus nephritis in systemic lupus erythematosus

Author information

Martin M1, Smoląg KI1, Björk A1, Gullstrand B2, Okrój M3, Leffler J4, Jönsen A2, Bengtsson AA2, Blom AM5. Arthritis Res Ther. 2017 Dec 6;19(1):266. doi: 10.1186/s13075-017-1470-2.

Abstract

1 Department of Translational Medicine, Section of Medical Protein Chemistry, Lund University, Inga Marie Nilsson's Street 53, 205 02, Malmö, Sweden.

2 Rheumatology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.

3 Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.

4 Telethon Kids Institute, University of Western Australia, Perth, Australia.

5 Department of Translational Medicine, Section of Medical Protein Chemistry, Lund University, Inga Marie Nilsson's Street 53, 205 02, Malmö, Sweden. anna.blom@med.lu.se.

Abstract

BACKGROUND: In the present study, we sought to evaluate the complement activation product C4d as a marker for lupus nephritis in systemic lupus erythematosus (SLE).

METHODS: C4d levels were determined by enzyme-linked immunosorbent assay in plasma samples of patients with established SLE using a novel approach based on detection of a short linear cleavage neoepitope. Cross-sectional associations were studied in 98 patients with SLE with samples taken at lower or higher respective disease activity. Temporal associations were investigated in 69 patients with SLE who were followed longitudinally for up to 5 years. Plasma samples from 77 healthy donors were included as controls.

RESULTS: C4d levels were negligible in healthy control subjects and significantly increased in patients with SLE in the cross-sectional study (p < 0.0001). C4d levels discriminated between higher and lower disease activity according to ROC curve analysis (p < 0.001), exhibiting a positive predictive value of 68%. At higher disease activity, C4d levels correlated with the modified Systemic Lupus Erythematosus Disease Activity Index (p = 0.011) and predominantly with lupus nephritis (p = 0.003), exhibiting a sensitivity of 79% to identify patients with nephritis. High C4d levels together with the presence of anti-dsDNA autoantibodies preceded and thus predicted future lupus nephritis in the longitudinal study (OR 5.4, 95% CI 1.4-21.3). When we considered only patients with renal involvement (19 of 69) during the longitudinal study, we found that high C4d levels alone could forecast recurrence of future lupus nephritis (OR 3.3, 95% CI 1.2-9.6).

CONCLUSIONS: C4d appears to be a valuable marker for use in monitoring of patients with SLE, particularly for lupus nephritis. Importantly, C4d levels can predict impending flares of lupus nephritis and may thus be useful for informing treatment.