The presence of antibodies against the chemokine receptors CXR3 and CXR4 correlates with the severity of interstitial lung disease related to systemic sclerosis, according to findings published in Arthritis Research and Therapy.
“C-X-C motif chemokine receptor (CXCR)3 and CXCR4 are G protein-coupled receptors (GPCRs) mediating the migration of different cells including lymphocytes, endothelial progenitor cells, and stem cells,” Florian Weigold, Dr. Med, of the Charité University Hospital, Berlin, Germany, and colleagues wrote. “Assuming the existence of antibodies against CXCR3 and CXCR4, our group has developed enzyme-linked immunosorbent assays (ELISAs) to measure their concentrations in sera.”
To determine whether anti-CXCR3/4 antibodies, and the corresponding receptors, could act as biomarkers for systemic sclerosis or related organ damage, the researchers studied 449 sera from 327 patients with systemic sclerosis from the Charité University Hospital, as well as 425 sera from 312 healthy donors. In patients with systemic sclerosis, investigators compared antibody levels with patients’ clinical data.
The presence of antibodies against the chemokine receptors CXR3 and CXR4 correlates with the severity of interstitial lung disease related to systemic sclerosis, according to researchers.
Further, the researchers, using flow cyometry, examined CXCR3/4 protein expression on peripheral blood mononuclear cells (PBMCs) in 17 patients with systemic sclerosis and in 8 of the healthy donors.
According to the researchers, anti-CXCR3 and anti-CXCR4 antibody levels were highest in diffuse patients with systemic sclerosis, and antibody levels strongly correlated with each other (r = 0.85). Patients with interstitial lung disease related to systemic sclerosis demonstrated higher antibody levels, which was negatively associated with lung function. The researchers also noted that patients with decreasing lung function demonstrated lower anti-CXCR3 and anti-CXCR4 antibody levels, compared with those with stable disease.
Additionally, frequencies and median fluorescence intensities of the PBMCs were lower in patients with systemic sclerosis, compared with healthy donors, and correlated with skin and lung fibrosis severity.
“We have identified novel anti-GPCR [antibodies] against the chemokine receptors CXCR3 and CXCR4 in patients with systemic sclerosis linking autoimmunity with interstitial lung disease,” Weigold and colleagues wrote. “Here, anti-CXCR3 and anti-CXCR4 antibody levels are shown to be very good markers of predicting lung fibrosis and are, therefore, candidates to stratify patients for disease progression, that is, in clinical trials.” – by Jason Laday
Disclosure: Weigold reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.