Selective APRIL blockade delays systemic lupus erythematosus in mouse

Area of Science:

• Immunology
• Rheumatology
• Molecular Biology

Background:

• Systemic lupus erythematosus (SLE) pathogenesis involves autoantibodies forming immune complexes, leading to tissue damage.
• A proliferation-inducing ligand (APRIL) promotes plasma cell survival and may prolong pathogenic autoantibody production in lupus.

Purpose of the Study:

• To investigate the role of APRIL in SLE pathogenesis using a NZB/W mouse model.
• To evaluate the therapeutic potential of APRIL blockade in treating lupus.

Main Methods:

• Quantified APRIL mRNA and protein levels in bone marrow and spleen cells of lupus mice and controls.
• Administered selective antibody-mediated APRIL blockade to lupus mice.
• Assessed disease progression, including proteinuria, kidney lesions, mortality, autoantibody levels, and B- and T-cell homeostasis.

Main Results:

• Elevated APRIL levels were observed in bone marrow cells of lupus mice.
• APRIL blockade significantly delayed SLE disease development, reducing proteinuria, kidney damage, and mortality.
• Treatment decreased anti-DNA and anti-chromatin autoantibody levels without altering B- and T-cell homeostasis.

Conclusions:

• APRIL blockade is a promising therapeutic strategy for SLE, specifically targeting plasma cells.
• This approach offers a potentially safer alternative to broad immunosuppressants, with fewer adverse effects.
• Targeting APRIL presents a novel, specific treatment avenue for managing autoantibody-driven diseases like lupus.