Autotaxin protein found at higher levels in women with SSc-ILD
Sex differences uncovered in US study for protein tied to wound healing
Autotaxin, a protein involved in wound healing and scarring, or fibrosis, was found at higher levels in women with systemic sclerosis-associated interstitial lung disease (SSc-ILD) than in men with the condition, per a new U.S. study.
According to the researchers, “this study is the first to report sex-specific … protein differences in patients with SSc-ILD.”
Overall, 40 proteins were found to be present at different levels in men and women with SSc-ILD, with the team noting that “none of these proteins have been previously associated with sex-related hormones.”
However, only autotaxin was shown to be present at “significantly different” levels between the sexes in a subsequent analysis, the researchers noted.
“These proteins could influence disease progression and treatment response and underscore the importance of personalized therapeutic strategies and further research into sex-related molecular pathways in SSc-ILD,” the team wrote.
Their study, “An exploratory analysis of differences in serum protein expression by sex in patients with systemic sclerosis associated interstitial lung disease,” was published in the journal BMC Pulmonary Medicine.
Men less likely to develop SSc, but more likely to have SSc-ILD
SSc, also known as scleroderma, is an autoimmune disease characterized by inflammation and fibrosis, or the accumulation of scar tissue, in the skin and internal organs, particularly the lungs. About 30% to 50% of SSc patients develop interstitial lung disease, or ILD, a group of conditions characterized by inflammation and scarring of the lungs.
Men are less likely to develop SSc. But previous studies have suggested that male patients are more prone to have SSc-ILD, and to develop it at a younger age, than female patients. The mortality rate also is higher in men.
“Even though … disease progression and severity differ between men and women, it remains unknown why these differences exist,” the researchers wrote.
To learn more, a team of U.S. scientists analyzed the differences in blood protein levels between men and women with SSc-ILD who were enrolled in the University of California, San Francisco Scleroderma Center registry.
More than 200 patients — 162 women and 47 men — with similar characteristics were involved in the study. Most (85%) were being treated with immunosuppressant therapies, with no significant difference between the percentage of men and women.
The participants were followed for a median of 3.5 years. During that time, 118 (56%) experienced a decline in forced vital capacity, or FVC, a measure of lung function, of at least 5%. The median time for lung function worsening was 2.1 years and also did not differ between men and women.
Additionally, 58 patients had an FVC decline of 10% after a median of 2.6 years, again with no sex differences.
Levels of autotaxin, 39 other proteins, found to differ between men and women
Among the patients, 72 had available blood samples. From these, more than 700 proteins were identified, 40 of which were significantly different between men and women.
A total of 17 proteins were present at higher levels in women, while 23 were elevated in men. After further testing, only the levels of autotaxin remained significantly elevated in women.
This protein is known to promote wound healing and deposits of collagen, a main component of scar tissue. Previous studies indicated that people with idiopathic pulmonary fibrosis, a type of ILD, have elevated levels of autotaxin.
Further research efforts should focus on the evaluation of differential pathways that may define sexual dimorphism [sex differences] in SSc-ILD.
Studies in mice also demonstrated that blocking autotaxin resulted in reduced lung fibrosis.
Altogether, “these findings suggest a potential role for autotaxin in modulating fibrotic processes in SSc-ILD, like its known associations in [idiopathic pulmonary fibrosis] and other fibrotic disorders,” the researchers wrote.
The team noted, as a “major limitation” of the study, its relatively small sample size. The researchers said future studies “could evaluate the relationship between these differentially-expressed proteins” — with a second look at differences that did not remain significant after additional analysis.
“Further research efforts should focus on the evaluation of differential pathways that may define sexual dimorphism [sex differences] in SSc-ILD, particularly in [not previously treated] patients,” the scientists concluded.
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