Pathogenesis of relapsing polychondritis: a 2013 update

Area of Science:

• Immunology
• Rheumatology
• Systemic Inflammatory Diseases

Background:

• Relapsing polychondritis (RP) is a rare systemic inflammatory disorder affecting cartilaginous tissues and other organs.
• The specific auto-antigens targeted in RP remain largely unknown.
• Evidence suggests both Collagen Type II (CII) and matrilin-1 as potential candidates.

Purpose of the Study:

• To investigate the immunological underpinnings of relapsing polychondritis.
• To identify potential auto-antigens and characterize the inflammatory pathways involved.
• To explore the role of cytokines and cellular recruitment in RP pathogenesis.

Main Methods:

• Analysis of serum cytokine levels in RP patients compared to healthy donors.
• Assessment of disease activity markers, including sTREM-1, interferon-gamma, and various chemokines.
• Review of existing data from human studies and murine models regarding potential auto-antigens.

Main Results:

• RP appears to be a Th1-mediated disease, with serum levels of IFN-γ, IL-12, and IL-2 correlating with disease activity.
• Elevated levels of sTREM-1, IFN-γ, CCL4, VEGF, and MMP-3 were observed in RP patients.
• Active RP cases showed significantly higher levels of MCP-1, MIP-1β, MIF, and IL-8, indicating monocyte and neutrophil recruitment.

Conclusions:

• A complex cytokine network orchestrates the infiltration of immune cells in RP lesions.
• Understanding the cellular repertoire and circulating mononuclear cells during flares can provide insights into RP auto-antigens and disease mechanisms.
• Targeted cytokine modulation therapies show promise but require further investigation.