A small study by researchers in Greece showed that B-cell depletion through “off-label” use of an approved drug may help to treat skin fibrosis in people with systemic sclerosis (SSc), and identified specific molecules of likely importance to this process. The article, “B cell depletion therapy upregulates Dkk-1 skin expression in patients with systemic sclerosis: association with enhanced resolution of skin fibrosis,“ was published in the journal Arthritis Research and Therapy.
B-cells are immune system cells that make antibodies, proteins that attack harmful substances and remove them from the body. But B-cells can be involved in harmful immune responses, contributing to diseases such as SSc, and causing the skin fibrosis (scarring) that occurs in this condition.
Rituximab (Rituxan, Genentech) is an approved drug to treat certain B-cell cancers, like non-Hodgkin lymphomas, and rheumatoid arthritis, and the researchers believe it might also help to reduce skin fibrosis in people with SSc. Led by Dimitrios Daoussis of the Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, they wanted to better understand how rituximab functions and to identify specific molecules that the drug activates.
Based on prior research, the scientists hypothesized that rituximab regulates a molecule called dickkopf-1 (Dkk-1), which inhibits a cellular pathway called the Wnt pathway. Ultimately, this may stop B-cells from causing fibrosis.
A total of 14 people with SSc participated in the study, and five healthy people served as controls. Scientists took skin samples from the SSc patients. After treatment with rituximab, four of the patients had an increase in Dkk-1 in their skin. These patients also had the greatest improvement in their skin condition, and exhibited a decrease in markers for B-cell activity, namely TGFβ (transforming growth-factor beta).
“This is the first study demonstrating a link between B cell depletion and skin Dkk-1 upregulation in patients with SSc,” the researchers wrote. “Moreover, patients with upregulation of Dkk-1 following [rituximab] treatment have the best histologic response to treatment.”
The findings could ultimately point toward new mechanisms for preventing skin fibrosis in SSc, and a possible new treatment for the disease. More research in larger groups of SSc patients, however, is needed.
SSc is a connective tissue disease that can involve many organs, including the skin, and is characterized by diseased blood vessels and fibrosis — the thickening and scarring of connective tissue.
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