Gene expression may potentially be used to stratify patients with systemic sclerosis
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It may be possible to use the signature of classical and non-classical circulating monocytes to stratify patients with systemic sclerosis and predict disease severity and outcomes, according to data published in Arthritis & Rheumatology.
“SSc is highly heterogenous in presentation and disease course, and may involve the skin, blood vessels, lungs, heart, kidneys, and gastrointestinal (GI) tract,” Hadijat-Kubura M. Makinde, PhD, of Northwestern University, and colleagues wrote. “SSc can be subtyped by cutaneous involvement, including limited (lcSSc), diffuse (dcSS), and non-cutaneous (ncSSc, more recently known as sine scleroderma). While clinically defined SSc cutaneous subsets are associated with internal organ complications and death, they cannot predict disease course on a per-patient basis or inform treatment decisions.
“Thus, identification of disease endophenotypes and their longitudinal course will facilitate precision medicine implementation,” they added.
To establish and verify new biomarkers to help categorize patients with SSc, Makinde and colleagues examined patient information from the Prospective Registry of Early Systemic Sclerosis. Patients were included if they had never received immunosuppressant therapy and planned to begin a new SSc therapy between September 2015 and June 2016. Administrators collected data, including Rodnan skin and pulmonary function test scores, and additionally recruited age-, sex- and ethnicity-matched controls.
Following isolation and collection, the researchers processed and stained the samples via fluorescence activated cell sorting, before assessing them via RNA sequencing. The researchers identified 431 classical and 388 non-classical circulating monocytes genes, and calculated each gene’s average expression for different patient groups, determining which genes were expressed in higher proportions in the trial group compared with the control group.
Patients were sorted into one of three groups based on their signatures compared with control patients. The sorting was conducted via clustering patients hierarchically based on genes that were differential in three or more patients.
According to the researchers, patients in groups B and C demonstrated worse lung function than patients in group A, but there was no clear distinction in skin disease at baseline.
“Clinical heterogeneity in SSc presentation has been well-characterized for decades, and differential gene expression has been demonstrated in fibrotic tissue; however, reproducible connections have not been established between transcriptomic intrinsic subsets and clinical characteristics, including prognosis and response to treatment,” Makinde and colleagues wrote. “A thorough molecular understanding of SSc may help to stratify patients for enrollment in clinical trials and to inform drug selection.”
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