Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• T peripheral helper (Tph) cells are implicated in rheumatoid arthritis pathogenesis by promoting B cell maturation and antibody production in non-lymphoid tissues.
• Juvenile oligoarthritis (oligo JIA) is an inflammatory arthritis where T cell-B cell interactions may be dysregulated.

Purpose of the Study:

• To investigate the role of Tph cells and T cell-B cell interactions in juvenile oligoarthritis (oligo JIA).
• To determine if Tph cells contribute to autoantibody production in oligo JIA.

Main Methods:

• Single-cell transcriptomics was used to analyze Tph cells in synovial fluid from oligo JIA patients.
• Comparison of Tph cell gene expression and accumulation in autoantibody-positive versus autoantibody-negative patients.

Main Results:

• Clonally expanded Tph cells that promote B cell antibody production were found preferentially in the synovial fluid of antinuclear antibody (ANA)-positive oligo JIA patients.
• Tph cells from ANA-positive patients showed upregulated genes associated with B cell help compared to ANA-negative patients.
• Tph-like regulatory T cells (Tregs) co-expressing B cell-help factors were identified, suggesting a potential regulatory role.

Conclusions:

• Disordered T cell-help to B cells plays a central role in autoantibody-positive arthritides, including oligo JIA.
• Tph cells are key drivers of B cell responses in the synovium of oligo JIA patients with autoantibodies.