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Clinical and immunological effects of anti-TNF therapy in systemic lupus erythematosus (SLE)
Arthritis Res Ther volume 5, Article number: 33 (2003)
Tumor necrosis factor (TNF) is increased in the sera of patients with SLE and in lupus glomerulonephritis and is associated with disease activity. We investigated clinical and immunological outcomes in a pilot trial of TNF blockade in SLE.
Within an open safety study, SLE patients with nephritis or arthritis receive the humanized chimeric anti-TNF antibody infliximab plus azathioprine or methotrexate. Serum TNF (sTNF)was measured by ELISA, the percentages of TNF-positive lymphocytes by fluorocytometry.
In the first two lupus nephritis patients treated with infliximab, proteinuria fell from 1.2 to 0.3 g/24 h and from 5.7 to 1.1 g/24 h, respectively, within 3 months after the start of therapy; the (normal) creatinine serum levels remained stable. Arthritis in a third SLE patient remitted under therapy but relapsed 8 weeks after the last infusion. Anti-dsDNA IgG antibodies increased transiently in all three patients at around week 10 of therapy. An increase in anti-histone antibodies (as well as anti-chromatin antibodies in two of the three patients) predated the increase in anti-dsDNA, which was not associated with increased disease activity. Interestingly, even the increase in anti-histone antibodies was predated by an increase in sTNF (mean ± SD of peak value 168 ± 114 pg/ml), while the percentage of lymphocytes carrying TNF decreased at the same time.
Anti-TNF therapy improves SLE glomerulonephritis and arthritis but leads to a transient increase in autoantibodies, which was not associated with flares in our patients. The observation that anti-dsDNA antibodies are predated by anti-histone antibodies and that this increase follows the changes in TNF suggests that TNF-blocking therapy is directly associated with an increase in anti-histone and a subsequent transient increase in anti-dsDNA antibodies.
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Aringer, M., Steiner, G., Graninger, W. et al. Clinical and immunological effects of anti-TNF therapy in systemic lupus erythematosus (SLE). Arthritis Res Ther 5, 33 (2003) doi:10.1186/ar663
- Systemic Lupus Erythematosus
- Tumor Necrosis Factor
- Systemic Lupus Erythematosus Patient