Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus erythematosus: relationship to neuropsychiatric symptoms

Annie George-Chandy¹^,2 , Estelle Trysberg³ and Kristina Eriksson¹

¹Department of Rheumatology and Inflammation Research, Guldhedsgatan 10A, 413 46 Gothenburg, Sweden

²Department of Infection Immunology, Statens Serum Institut, Artillerivej 5, 232 300 Copenhagen, Denmark

³Rheumatogy Unit at Karolinska University Hospital/Huddinge, Hälsovägen 141, 141 52 Huddinge, Sweden

author email corresponding author email

Arthritis Research & Therapy 2008, 10:R97doi:10.1186/ar2484


Published:	22 August 2008

Abstract

Introduction

The tumour necrosis factor (TNF) family ligands BAFF (B-cell activating factor of TNF family) and APRIL (a proliferation-inducing ligand) are essential for B-cell survival and function. Elevated serum levels of BAFF and APRIL have been reported earlier in patients with systemic lupus erythematosus (SLE). Since autoantibody formation in the central nervous system (CNS) is a distinct feature of neuropsychiatric SLE (NPSLE), we have investigated whether NPSLE is associated with an enhanced intrathecal production of APRIL and BAFF.

Methods

Levels of BAFF and APRIL in cerebrospinal fluid (CSF) and serum from healthy controls, SLE patients without CNS involvement, and patients with NPSLE were determined by enzyme-linked immunosorbent assay. Interleukin-6 (IL-6) levels were determined by an IL-6-specific bioassay.

Results

SLE patients had levels of APRIL in CSF that were more than 20-fold higher and levels of BAFF in CSF that were more than 200-fold higher than those of healthy controls. Separate analyses of SLE patients with and without CNS involvement revealed that NPSLE patients had enhanced levels of APRIL in CSF. BAFF and APRIL were likely produced locally in the CNS as CSF and serum levels did not correlate. Moreover, CSF levels of APRIL correlated with BAFF but not with IL-6, suggesting that APRIL and BAFF in the CNS are regulated together but that they are produced independently of IL-6.

Conclusion

To our knowledge this is the first study to show elevated levels of BAFF and APRIL in CSF of SLE patients. APRIL was augmented in NPSLE patients compared with SLE patients without CNS involvement. APRIL and BAFF antagonists breeching the blood-brain barrier therefore could have beneficial effects on SLE patients, in particular patients with NPSLE.