Increased Complement 3a Receptor is Associated with Behcet's disease and Vogt-Koyanagi-Harada disease

Area of Science:

• Immunology
• Autoimmune Diseases
• Ophthalmology

Background:

• Behcet's disease (BD) and Vogt-Koyanagi-Harada disease (VKH) are systemic autoimmune disorders characterized by abnormal T cell responses.
• Complement receptors, including complement 3a receptor (C3aR) and complement 5a receptor (C5aR), are implicated in T cell-mediated autoimmune conditions.

Purpose of the Study:

• To investigate the expression and role of C3aR and C5aR in the pathogenesis of active Behcet's disease (aBD) and active Vogt-Koyanagi-Harada disease (aVKH).

Main Methods:

• Quantification of C3aR and C5aR expression in peripheral blood mononuclear cells (PBMCs) from patients with active BD, active VKH, and healthy controls.
• Analysis of C3aR expression following control of intraocular inflammation.
• In vitro studies assessing the effects of patient serum and C3a on PBMC cytokine production and T cell responses.

Main Results:

• Elevated C3aR expression was observed in PBMCs of patients with active BD and active VKH, returning to normal levels after inflammation control.
• C5aR expression showed no significant difference between patients and controls.
• Patient serum induced C3aR expression in PBMCs; C3a stimulation promoted pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and inhibited IL-10 production.
• C3aR activation in CD4+ T cells upregulated IL-17 and inhibited IL-10 production.

Conclusions:

• Increased C3aR expression in BD and VKH patients correlates with active disease and may contribute to pathogenesis.
• The findings suggest that C3aR activation promotes Th17 cell responses, potentially driving the autoimmune processes in BD and VKH.