High Levels of Specific Antibodies Associated with Worsening Lung Function in Systemic Sclerosis Patients

A recent study showed that worsening symptoms of lung fibrosis in systemic sclerosis patients is linked to high levels of antibodies against the chemokine receptors Cxcr3 and Cxcr4.

The results were revealed at the 4^th Systemic Sclerosis World Congress held in Lisbon, Portugal, Feb. 18-20 in the presentation “Antibodies against chemokine receptors Cxcr3 and Cxcr4 as marker for lung fibrosis in patients with systemic sclerosis.”

Cxcr3 and Cxcr4 are key chemokine receptors that play important roles in the trafficking and function of immune cells, as chemokines drive immune cells to sites of inflammation. These particular receptors were shown to be involved in fibrosis development in systemic sclerosis patients. Previous reports suggested that antibodies against Cxcr3 and Cxcr4 receptors are present in systemic sclerosis patients and correlate with clinical symptoms.

A team of researchers tackled this issue and analyzed 425 serum samples from 312 systemic sclerosis patients for antibodies against Cxcr3 and Cxcr4 (anti-Cxcr3 and anti-Cxcr4), and the same procedure was followed in healthy controls. The levels of antibodies in systemic sclerosis patients were then correlated with patients’ clinical data for disease symptoms and severity. Researchers also measured the expression of Cxcr3 and Cxcr4 in monocytes, a type of white blood cell, and compared it to clinical data.

The team found that the levels of anti-Cxcr3 and anti-Cxcr4 differed between healthy controls and systemic sclerosis patients, with the latter expressing higher levels, particularly those with diffuse systemic sclerosis — a subtype of systemic sclerosis that involves the skin of the proximal extremities and trunk, also associated with internal organ involvement.

The levels of both antibodies correlated with each other and with negative lung function parameters. Specifically, a particular correlation was observed between anti-Cxcr3 and anti-Cxcr4 levels and predicted vital capacity — a parameter that denotes the maximum amount of air a person can expel from the lungs after a maximum inhalation.

Researchers also observed that higher levels of antibodies were found in patients with lung fibrosis and muscular symptoms, and low levels of anti-Cxcr3 were found in patients with secondary Sjoegren’s syndrome (a condition that often accompanies immune disorders, often characterized by less moist mucous membranes, resulting in impaired production of tears and saliva), osteoarthritis, and fibromyalgia.

Patients with high levels of anti-Cxcr3 and anti-Cxcr4 presented higher risks for continued lung deterioration compared to those with lower levels.

The results of the study suggested that antibodies against Cxcr3 and Cxcr4 correlate with worsening manifestations of systemic sclerosis, particularly lung fibrosis.