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Ann Rheum Dis. Sep 2004; 63(9): 1096–1103.
PMCID: PMC1755113

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

Abstract

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.

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Selected References

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Figures and Tables

Figure 1
 Heterogeneity in serum APRIL phenotypes among patients with SLE and relation to disease activity. (A) Serum samples collected from three representative normal controls (circles, triangles, squares) were assayed for APRIL levels. By definition, ...
Figure 2
 Relation between serum APRIL and serum BLyS levels. Serum samples collected from two representative normal controls (A, B) and four representative patients with SLE (C–F) were assayed for APRIL and BLyS levels. The dotted lines delineate ...
Figure 3
 Insensitivity of serum APRIL levels to treatment with high dose corticosteroids. Nine patients with SLE were treated with short courses of high dose corticosteroids.15 BLyS levels in pretreatment (B-pre) and post-treatment (B-post) serum samples ...
Figure 4
 Heterogeneity in blood APRIL mRNA phenotypes among patients with SLE. (A) Peripheral blood samples collected from the same three representative normal controls illustrated in fig 1A (circles, triangles, squares) were assayed for APRIL mRNA levels. ...
Figure 5
 Relation between blood APRIL mRNA levels and blood BLyS mRNA levels. (A–D) Blood collected from two representative normal controls (A, B) and two representative patients with SLE (C, D) were assayed for APRIL mRNA and BLyS mRNA. The ...
Figure 6
 Relation between serum APRIL levels and serum anti-dsDNA titres. (A, B) Serum APRIL levels (filled circles) and serum anti-dsDNA titres (open squares) were determined in two representative patients with SLE in whom changes in serum APRIL levels ...

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