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Open Access Research article

Synovial tissues concentrate secreted APRIL

Cem Gabay12, Veit Krenn3, Carine Bosshard24, Christian Alexander Seemayer56, Carlo Chizzolini7 and Bertrand Huard24*

Author Affiliations

1 Division of Rheumatology, University Hospitals, 4 rue Gabrielle Perret-Gentil, Geneva, CH 1211, Switzerland

2 Department of Pathology-Immunology, Faculty of Medicine, 1 rue Michel Servet, Geneva, CH 1211, Switzerland

3 Cytology and Molecular Diagnostic, Histology Center, Max Planck Street, Trier D-54296, Germany

4 Division of Hematology, 4 rue Gabrielle Perret-Gentil, Geneva, CH 1211, Switzerland

5 Department of Pathology, Faculty of Medicine, 1 rue Michel Servet, Geneva, CH 1211, Switzerland

6 Current address: Rheumatology, University Hospitals, 46 rue du Bugnon, Lausanne, CH 1011, Switzerland

7 Division of Immunology and Allergy, 4 rue Gabrielle Perret-Gentil, Geneva, CH 1211, Switzerland

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Arthritis Research & Therapy 2009, 11:R144  doi:10.1186/ar2817

Published: 29 September 2009

Abstract

Introduction

A proliferation-inducing ligand (APRIL) from the TNF family, owing to its role in the generation and survival of plasma cells (PCs), is currently targeted for rheumatoid arthritis (RA) treatment. However, little is known about APRIL expression in RA lesions, hampering our understanding of the way APRIL may modulate this autoimmune disease.

Methods

We performed immunological staining of human normal, non-RA and RA synovial tissues with a pair of antibodies specifically recognizing APRIL-producing cells and secreted APRIL.

Results

We detected significant amounts of secreted APRIL in normal synovium mostly concentrated around blood vessels and at the lining layer, but no cells producing APRIL. Meanwhile, we observed that blood neutrophils constitutively secrete APRIL, indicating that blood APRIL may diffuse into the synovium via its fenestrated vessels. Synovium from non-RA and RA patients retained similarly secreted APRIL, but in this case APRIL-producing cells, including neutrophils and macrophages, were present in the tissue. Notably, PCs - when present in RA synovium - accumulated in areas of APRIL retention, spreading from blood vessels towards the lining layer.

Conclusions

PCs accumulate in synovial zones rich in secreted APRIL, consistent with a pro-survival role of APRIL for PCs in RA. The concentration of APRIL by normal synovium indicates that this tissue may constitute a proper environment for PCs even before RA onset.