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Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus

¹ Division of Rheumatology, Department of Medicine, Los Angeles County + University of Southern California Medical Center and University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
² Human Genome Sciences, Inc, Rockville, MD 20850, USA

Correspondence to:
Correspondence to:
Dr W Stohl
Division of Rheumatology, University of Southern California, 2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033, USA; stohl{at}usc.edu

Objective: To assess longitudinal expression of a proliferation-inducing ligand (APRIL) in patients with systemic lupus erythematosus (SLE) and its correlation with B lymphocyte stimulator (BLyS) expression, serum anti-dsDNA titres, and clinical disease activity.

Methods: Sixty eight patients with SLE were longitudinally followed up for a median of 369 days. At each visit the physician assessed disease activity by SLEDAI, and blood was collected for determination of serum APRIL and BLyS levels and of blood APRIL and BLyS mRNA levels. Fifteen normal control subjects underwent similar laboratory evaluation.

Results: Dysregulation of APRIL was not as great as that of BLyS. Changes in serum levels of APRIL and BLyS over time were usually discordant, whereas blood levels of APRIL and BLyS mRNA strongly paralleled each other. Serum APRIL levels modestly, but significantly, inversely correlated with serum anti-dsDNA titres in anti-dsDNA positive patients analysed in aggregate. Moreover, serum APRIL levels modestly, but significantly, inversely correlated with clinical disease activity in all patients analysed in aggregate.

Conclusion: Serum levels of APRIL and BLyS are differentially regulated. APRIL may serve as a down modulator of serological and/or clinical autoimmunity in patients with SLE. This may have important ramifications for BLyS targeted treatment, and it remains to be determined whether agents which neutralise only BLyS will be preferable to agents which neutralise both BLyS and APRIL.

Abbreviations: APRIL, a proliferation-inducing ligand; BLyS, B lymphocyte stimulator; ELISA, enzyme linked immunosorbent assay; IFN, interferon; SLE, systemic lupus erythematosus; SLEDAI, SLE Disease Activity Index; TNF, tumour necrosis factor

Keywords: B lymphocyte stimulator (BLyS); APRIL; systemic lupus erythematosus; anti-dsDNA antibodies; disease activity

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