Synovial tissues concentrate secreted APRIL.

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• A proliferation-inducing ligand (APRIL) is a TNF family member crucial for plasma cell (PC) generation and survival.
• APRIL is a therapeutic target for rheumatoid arthritis (RA).
• The expression and role of APRIL in RA synovial lesions remain poorly understood.

Purpose of the Study:

• To investigate the expression and localization of APRIL and APRIL-producing cells in normal, non-RA, and RA synovial tissues.
• To understand the potential role of APRIL in modulating rheumatoid arthritis pathogenesis.

Main Methods:

• Immunohistochemical staining of human synovial tissues (normal, non-RA, RA) using antibodies against APRIL and APRIL-producing cells.
• Detection of secreted APRIL and cellular sources of APRIL, including neutrophils, macrophages, and plasma cells.

Main Results:

• Secreted APRIL was detected in normal synovium, primarily around blood vessels and the lining layer.
• Blood neutrophils constitutively secrete APRIL, suggesting diffusion into the synovium.
• RA and non-RA synovium showed similar secreted APRIL levels, but RA synovium contained APRIL-producing neutrophils and macrophages.
• Plasma cells in RA synovium localized to areas of APRIL retention, particularly near blood vessels and the lining layer.

Conclusions:

• Plasma cells accumulate in APRIL-rich synovial areas, supporting a pro-survival role for APRIL in RA.
• The normal synovium concentrates APRIL, indicating it may provide a supportive environment for plasma cells even before RA onset.