Synovial tissues concentrate secreted APRIL.
BACKGROUND
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.
Gabay
Cem
C
Division of Rheumatology, University Hospitals, 4 rue Gabrielle Perret-Gentil, Geneva, CH 1211, Switzerland. Cem.Gabay@hcuge.ch
Krenn
Veit
V
Bosshard
Carine
C
Seemayer
Christian Alexander
CA
Chizzolini
Carlo
C
Huard
Bertrand
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D010950:Plasma Cells / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism*
D053300:Tumor Necrosis Factor Ligand Superfamily Member 13