Clinical and immunological effects of anti-TNF therapy in systemic lupus erythematosus (SLE)

Background

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.

Methods

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.

Results

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.

Conclusion

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.