Researchers at Germany’s University of Luebeck and Charité University recently presented a study where they reported that circulating antibodies against specific chemokine (small proteins with an important role in the immune system) receptors exist in higher levels in patients with systemic sclerosis, and these antibodies correlate with disease progression and clinical manifestations of the disease, such as lung fibrosis.
The study was presented at the 4th Systemic Sclerosis World Congress in Lisbon, Portugal, Feb. 18-20, and was titled “Antibodies Against Chemokine Receptors CXCR3 and CXCR4 as Marker for Lung Fibrosis in Patients with Systemic Sclerosis.”
Systemic sclerosis, or scleroderma, is a chronic connective tissue disease characterized by the hardening and tightening of the skin. Inflammation and development of fibrotic tissue are also features of the disease. Chemokines are essential to the migration of pro-inflammatory immune cells to the sites of inflammation.
The immune cells have chemokine receptors in their surface that allow such responses to happen. Two of these chemokine receptors, CXCR3 and CXCR4, are known to be involved in fibrotic events as well as angiogenesis (formation of blood capillaries), which is known to be altered in systemic sclerosis. Now there is a theory that antibodies targeting these receptors might be associated with fibrotic mechanisms.
The research team investigated the clinical significance of CXCR3 and CXCR4 receptors and corresponding antibodies. Blood was collected from 312 systemic sclerosis patients and 234 healthy donors, and the levels of anti-CXCR3 and anti-CXCR4 antibodies were measured and compared with clinical data. The expression of the receptors on immune cells called monocytes was also determined.
Results showed that the level of antibodies, which strongly correlated with each other, were different between systemic sclerosis patients and healthy subjects, being significantly higher in patients with diffuse disease.
Also, the levels of anti-CXCR3 and anti-CXCR4 antibodies negatively correlated with lung function parameters, such as predicted vital capacity. Higher levels of antibodies were found in patients that exhibited lung fibrosis and muscular symptoms, and patients with higher antibody levels showed increased likelihood for further lung deterioration than patients with lower antibody levels. CXCR4 expression was higher in patients exhibiting digital ulcers and cardiac involvement.
Based on the results, the research team concluded in their presentation’s abstract that the “percentages of PBMC [peripheral blood mononuclear cell] expressing CXCR3 and CXCR4 receptors and the corresponding autoantibodies are linked with clinical manifestations in systemic sclerosis, mainly with signs of lung fibrosis and with the progress of the disease.”
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