Epitope-based blood test may identify active systemic sclerosis

MADRID — A conformational epitope-based assay may be effective in identifying systemic sclerosis patients whose disease is active, regardless of whether their condition is classified as limited or diffuse, according to a study presented at the EULAR Congress, here.

“Currently, there is no single blood test or biomarker that can predict progression of systemic sclerosis,” presenter Gianluca Moroncini, MD, PhD, of Università Politecnica Marche, Ancona, Italy, said in a press conference. “Nobody can predict right now if Reynaud’s phenomenon is primary, or if it will evolve toward scleroderma or systemic sclerosis.”

In the study, researchers screened the large platelet-derived growth factor receptor-alpha (PDGFR-alpha) peptide library used for epitope mapping of monoclonal anti-PDGFR-alpha antibodies for samples from 25 systemic sclerosis (SSc; 12 limited, 13 diffuse) and 25 healthy control serum samples. In this library, the researchers identified a specific peptide that could distinguish blood samples of patients with SSc from those of healthy controls.

Researchers screened a smaller PDGFR-alpha consisting of only the top 20 conformational binders. As well as 20 linear controls and 20 conformational controls. The screening of this laboratory confirmed the identity of the immunodominant peptide.

Statistical analysis revealed two subgroups of SSc samples: reactive and nonreactive.

In a third library, the researchers detected the chimeric peptide recognized only by reactive SSc serum samples. These samples came from patents with active, progressive SSc, regardless of whether they were classified as limited or diffuse. Conversely, the nonreactive SSc samples came from patients with less active, non-progressive disease.

The researchers have used the immunodominant epitope to develop a test that detects SSc-specific antibodies.

“The general idea is that scleroderma patients and controls can have antibodies against this receptor, but while some antibodies bind in an innocent region of this receptor, scleroderma patients are characterized by stimulatory antibodies that induce fibrosis,” Moroncini said. “The idea is to exploit this epitope to detect and identify scleroderma patients who have this antibody.”

The prototype test may be useful in identifying patients with active disease, regardless of whether they are classified as limited or diffuse, Moroncini said.
“We will need to validate this tool in larger groups of patients, to see if the test can identify very early-stage patients and predict whether they are going to worsen in their disease,” he said. — by Jennifer Bryne

Reference:

Moroncini G, et al. Abstract #OP0031. Presented at: EULAR Annual Congress; June 14-17, 2017; Madrid.

Disclosure: Moroncini reports no relevant disclosures.