Despite differing reports within the scientific community, a new study confirms that serum levels of the TGF-β1 cytokine are significantly higher in patients with systemic sclerosis (SSc). Cytokines are small proteins secreted by certain cells of the immune system that impact other cells.
Transforming growth factor beta (TGF-β) is a signaling molecule that once released from cells can activate neighboring or distant cells. It is thought to play a pro-fibrotic role in SSc. Three major forms of TGF-β exist: TGF-β1, TGF-β2, and TGF-β3, each with distinct expression patterns.
Although each of the three isoforms have been associated with SSc, TGF-β1 is the most extensively studied and was the focus of the study titled “Reassessing the Role of the Active TGF𝛽1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations,” published in the journal Disease Markers.
Because of the contradictory scientific literature, the study’s authors wanted to more fully understand the role of TGF-β1 in SSc. They recruited 56 patients with SSc along with 24 healthy people, or controls. Most of the patients in the study were female (94.6%).
SSc can be subdivided into two major subtypes: diffuse cutaneous systemic sclerosis (dSSc) and limited cutaneous systemic sclerosis (lSSc). Just over half of the patients in the study (53.6 %) had lSSc.
The researchers looked at different biological sources of TGF-β1 including serum, skin from SSc patients, and levels secreted by patients’ peripheral blood mononuclear cells (PBMCs) in in vitro cultures. They correlated levels of the cytokine with clinical parameters.
Compared to healthy controls, patients with SSc had significantly higher levels of TGF-β1 in their serum. In patients with lung fibrosis, digital ulcers, or who were positive for anti-toperisomerase I antibodies (autoantibodies found in several diseases, especially in SSc), serum levels of TGF-β1 were also significantly elevated compared to patients who did not possess these clinical manifestations.
After correcting for age, gender, disease duration and treatment, the researchers found higher serum levels of active TGF-β1 to be independently associated with lung fibrosis. Previous studies also suggested that TGF-β1 levels correlate with idiopathic pulmonary fibrosis, and the present study supports this claim.
In addition, the presence of autoantibodies such as the anti-toperisomerase I are also independently associated with elevated levels of TGF-β1 in the serum of patients with SSc. These autoantibodies attack self-proteins and contribute toward inflammation. They are associated with lung fibrosis and diffuse skin involvement.
Higher levels of the TGF-β1 cytokine in serum were also found in patients with dSSc compared to patients with lSSC, after correcting for confounding factors.
The authors identified no significant differences when assessing TGF-β1 levels in skin biopsies or the levels of secreted TGF-β1 from patients’ PBMCs cultures. A small sample size and technical limitations may explain the lack of significant data using these biological sources.
Regardless, the significantly increased TGF-β1 levels in the serum of SSc patients provides confirmation that this cytokine plays a role in systemic sclerosis.
“Taken together, our findings demonstrated raised active TGF-𝛽1 serum levels in SSc patients,” the team wrote. “Furthermore, we showed a significant association between active TGF-𝛽1 serum levels and vascular (digital ulcers) and fibrotic (lung and skin) manifestations in SSc patients, suggesting that raised levels could be evaluated as a marker of advanced disease.”