Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis - PubMed (original) (raw)

Clinical Trial

Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis

Therese Vallerskog et al. Arthritis Res Ther. 2006.

Abstract

The objective of this study was to investigate the interaction between levels of BAFF (B-cell activation factor of the tumour necrosis factor [TNF] family) and APRIL (a proliferation-inducing ligand) and B-cell frequencies in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) treated with the B-cell-depleting agent rituximab. Ten patients with SLE were treated with rituximab in combination with cyclophosphamide and corticosteroids. They were followed longitudinally up to 6 months after B-cell repopulation. Nine patients with RA, resistant or intolerant to anti-TNF therapy, treated with rituximab plus methotrexate were investigated up to 6 months after treatment. The B-cell frequency was determined by flow cytometry, and serum levels of BAFF and APRIL were measured by enzyme-linked immunosorbent assays. BAFF levels rose significantly during B-cell depletion in both patient groups, and in patients with SLE the BAFF levels declined close to pre-treatment levels upon B-cell repopulation. Patients with SLE had normal levels of APRIL at baseline, and during depletion there was a significant decrease. In contrast, patients with RA had APRIL levels 10-fold higher than normal, which did not change during depletion. At baseline, correlations between levels of B cells and APRIL, and DAS28 (disease activity score using 28 joint counts) and BAFF were observed in patients with RA. In summary, increased BAFF levels were observed during absence of circulating B cells in our SLE and RA patient cohorts. In spite of the limited number of patients, our data suggest that BAFF and APRIL are differentially regulated in different autoimmune diseases and, in addition, differently affected by rituximab treatment.

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Figures

Figure 1

Serum cytokine levels at B-cell-related time points. Left panels: levels of (a) BAFF and (b) APRIL in patients with systemic lupus erythematosus (SLE) at baseline (n = 10), depletion (n = 8), repopulation (n = 7), and recovery (n = 9). A significant increase compared with baseline was observed in BAFF at depletion (p < 0.01) and at repopulation (p < 0.05). In APRIL, a significant decrease (p < 0.05) occurred at depletion compared with baseline. Left panels: levels of (c) BAFF and (d) APRIL in patients with rheumatoid arthritis (RA) at baseline (n = 9), depletion (n = 8), and 6 months after infusion (n = 5). There was a significant increase (p < 0.01) in BAFF levels at depletion compared with baseline. Middle panels: longitudinal levels of BAFF and APRIL in patients with (a, b) SLE and (c, d) RA; each line corresponds to a different patient. The y-axis has the same scale as the axis in the box-plots. Right panels: relative changes compared with baseline of BAFF and APRIL in patients with (a, b) SLE and (c, d) RA. Relative change = sample X/baseline sample. The grey bar on the y-axis illustrates the level in healthy controls (*p < 0.05, **p < 0.01). APRIL, a proliferation-inducing ligand; BAFF, B-cell activation factor of the tumour necrosis factor family.

Figure 2

Relation between cytokine levels and B-cell frequency. (a) Two patients with systemic lupus erythematosus (SLE) (S5 and S14) representing the relation of B-cell frequency (left y-axis in diagrams) and cytokine levels (right y-axis) of BAFF (top row) and APRIL (bottom row) at B-cell-related time points. Dashed line depicts the cytokine level, and the unbroken line depicts the B-cell frequency. (b) Two patients with rheumatoid arthritis (RA) (R17 and R3) representing the relation of B-cell frequency (left y-axis) and levels of cytokines (right y-axis) BAFF (top row) and APRIL (bottom row) at baseline, depletion, and 6 months after treatment. APRIL, a proliferation-inducing ligand; BAFF, B-cell activation factor of the tumour necrosis factor family.

Figure 3

Correlations of BAFF (B-cell activation factor of the tumour necrosis factor family) and APRIL (a proliferation-inducing ligand). (a) Negative correlation of the B-cell frequency and APRIL levels in serum at baseline in patients with rheumatoid arthritis (RA) (Spearman r [rs] = -0.8, p < 0.05). (b) There was also a correlation between the number of B cells and levels of APRIL in serum at baseline in the patients with RA (rs = -0.67, p < 0.05). (c) Moreover, a correlation between the disease activity score using 28 joint counts (DAS28) and circulating levels of BAFF at baseline in patients with RA was found (rs = 0.76, p < 0.05). Each dot represents a different patient, and the line illustrates the slope of r.

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Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis - PubMed (original) (raw)