CEACAM 1, 3, 5 and 6 -positive classical monocytes correlate with interstitial lung disease in early systemic...

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Systemic sclerosis (SSc) is a multi-organ disease marked by vascular damage, autoimmunity, and fibrosis, often leading to poor prognosis due to organ injuries like interstitial lung diseases (ILD).
• While autoantibodies are present in SSc patients, the precise mechanisms of immune cell involvement in tissue inflammation and fibrosis remain unclear.
• Previous research implicated carcinoembryonic antigen related cell adhesion molecule (CEACAM)-positive monocytes in murine lung fibrosis, prompting investigation into their role in human SSc.

Purpose of the Study:

• To investigate the presence and role of CEACAM-positive monocytes in the pathogenesis of systemic sclerosis (SSc).
• To determine the correlation between CEACAM-positive monocyte proportions and clinical parameters in SSc patients.
• To analyze the functional characteristics and tissue infiltration of CEACAM-positive monocytes in SSc.

Main Methods:

• Flow cytometry was used to quantify CEACAM-positive classical monocytes in healthy controls (HCs), rheumatoid arthritis (RA) patients, and SSc patients.
• Correlation analyses were performed between monocyte proportions and clinical parameters (ESR, IgG, KL-6, %FVC) in SSc patients.
• Gene expression microarrays, immunohistochemical staining of skin biopsies, and in vitro assays using HCs' monocytes stimulated with SSc serum were conducted.

Main Results:

• Patients with early SSc (within 2 years of diagnosis) showed increased CEACAM-positive classical monocytes, correlating with higher ESR, IgG, KL-6, and lower %FVC.
• The proportion of CEACAM-positive monocytes decreased following immunosuppressive therapy.
• CEACAM6-positive monocytes were significantly elevated in SSc patients compared to HCs and RA patients, infiltrated SSc skin, produced higher levels of TNF-α and IL-1β, and exhibited NF-κB pathway activation.

Conclusions:

• CEACAM-positive monocytes exhibit inflammatory phenotypes and are implicated in the tissue inflammation and fibrosis observed in early SSc.
• These monocytes may serve as potential biomarkers for identifying SSc patients with progressive interstitial lung disease (ILD) who require therapeutic intervention.