BASIC AND TRANSLATIONAL RESEARCH

Serum levels of tumour necrosis factor family members a proliferation-inducing ligand (APRIL) and B lymphocyte stimulator (BLyS) are inversely correlated in systemic lupus erythematosus

J Morel^1,2, C Roubille¹, L Planelles³, C Rocha⁴, L Fernandez³, C Lukas¹, M Hahne, B Combe²

¹ Service d’Immuno-Rhumatologie Université Montpellier 1 et CHU Montpellier, Montpellier, France
² Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Montpellier, France
³ Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain
⁴ Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

Dr J Morel, Department of Immuno-Rheumatology, Montpellier I University and Lapeyronie Teaching Hospital, 34295 Montpellier, Cedex 5, France; j-morel{at}chu-montpellier.fr

Objective: To determine whether serum levels of a proliferation-inducing ligand (APRIL) are altered in patients with systemic lupus erythematosus (SLE), and correlate with disease parameters.

Methods: Clinical and biological parameters were analysed for 43 patients that fulfilled American College of Rheumatology (ACR) criteria for SLE classification and were positive for anti-double-stranded DNA (dsDNA) antibodies at least once in their medical records. Tests included measurement of serum levels of the tumour necrosis factor (TNF) family members APRIL and B lymphocyte stimulator (BLyS; a cytokine shown to promote SLE disease).

Results: Median APRIL levels were elevated in patients with SLE compared to patients with osteoarthritis and healthy controls, but did not correlate with the SLE Disease Activity Index (SLEDAI). APRIL serum levels showed an inverse correlation with BLyS serum levels (r = –0.339; p = 0.03). For patients with SLE with positive anti-dsDNA titres (>40 arbitrary units (AU)/ml) at inclusion (n = 25), circulating APRIL was inversely correlated with BLyS levels (r = –0.465; p = 0.022) and anti-dsDNA antibody titres (r = –0.411; p = 0.046). In a follow-up study at their second visit, 27 patients showed an inverse correlation of APRIL serum levels with BLyS (r = –0.398; p = 0.03) as well as with anti-dsDNA (r = –0.408; p = 0.03) titres and SLEDAI (r = –0.408; p = 0.01).

Conclusion: The inverse correlation observed between APRIL and BLyS suggests that APRIL acts as a protective factor. APRIL and BLyS may thus have opposite roles in SLE, which must be considered when defining therapeutic applications of these cytokines.

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