Table 1. Factors involved in PBC and SSc pathogenesis.

PBC: primary biliary cholangitis; SSc: systemic sclerosis; TGF-β: transforming growth factor-beta; IL: interleukin; TNFα: tumor necrosis factor-alpha; EBV: Epstein-Barr virus; CMV: cytomegalovirus.

Factor	Source/trigger	Role in PBC	Role in SSc
TGF-β [4,9,17]	Fibroblasts, immune cells	Promotes fibrosis and biliary epithelial cell injury	Promotes systemic fibrosis
IL-6 [9,19]	Immune cells	Drives inflammation and fibrosis
TNFα [9,19]	Immune cells	Promotes disease progression and loss of self-tolerance	Type I collagen production by fibroblast and mediates vasculopathy and fibrosis
IL-2R [9,19]	Immune cells	Decreases Treg cells and promotes autoimmunity	Secretes immunomodulatory factors by stimulating epithelial and endothelial cells and fibroblasts
IL-17 [4,16]	Immune cells	Pro-inflammatory factor and induces inflammation	Alleviates immune and inflammatory response
CD40L [16]	Immune cells	Regulates T-cell autoreactivity	Promotes autoimmunity
Smoking [16,20]	Environmental	Increases oxidative stress and promotes autoimmunity	Enhances vascular damage and fibrosis
UV exposure [16,20]	Environmental	Triggers DNA damage and promotes autoimmunity	Induces oxidative stress and promotes autoimmunity
EBV, CMV [9,19]	Environmental	Triggers disease by molecular mimicry	Antibodies directed against viral protein UL94 cross reacts with NAG-2, expressed by endothelial cells and fibroblasts
HDAC7 suppression [16,21]	Epigenetic	Decreases type I/III collagen production and modulates T-cell autoreactivity	Modulates fibrosis and immune responses
H4ac [16,21]	Epigenetic	Induces CD40L and IL-17, suppresses the TNF-related apoptosis-inducing ligand (TRAIL), and regulates T-cell autoreactivity	Progression of disease activity