Researchers have also found that castrated male mice have arthritis scores similar to female mice—low testosterone essentially feminizes the arthritis phenotype. They found a similar effect when looking at the percentage of diseased lung in the mice, and they noted that a lack of testosterone doesn’t bring about the fibrotic lung disease typically seen in aged mice.
“We believe that the SKG mouse is a really good model” for studying RA-related interstitial lung disease, Dr. Keith said. “Surgical castration, or lack of testosterone, in this mouse actually generates more feminine type of phenotype in which there’s increased arthritis severity and prevalence compared to male [mice], but lack of testosterone does not induce that fibrotic lung phenotype. So, as we move forward with these studies, we’re interested in looking at other mechanisms.”
Markers of RA-related Lung Disease
ILD stemming for RA can have devastating effects, making this complication one of the leading causes of morbidity and mortality in RA.
Researchers at the University of Miami are looking for noninvasive peripheral biomarkers to give doctors a marker for disease before it emerges clinically and may no longer be amenable to meaningful treatment. They are also hoping to use autoantibody profiles to show that tissue-specific patterns of protein citrullination distinguish RA patients who do and do not have ILD.
RA-related ILD accounts for between 10% and 20% of mortality in RA patients, making it crucial to find early clues. Getting clues about the precise nature of the lung disease is important because the histopathological subtype influences survival and outcomes for patients, said Dana Ascherman, MD, associate professor of medicine at the University of Miami’s Miller School of Medicine.
In their search for biomarkers, researchers anticipate that expression of CXCR3-binding chemokines and of certain metalloproteinases will be upregulated in cases of RA with ILD. They also anticipate that more extensive biomarker profiles obtained using enzyme-linked immunosorbent assay (ELISA) will differ according to the subtype of the disease. “The point of this effort is not simply to establish biomarkers of these different stages of lung disease but hopefully to gain insight regarding molecular pathways in the process,” Dr. Ascherman said.
Regarding autoantibody profiling, he said there is opportunity for advance even though previous studies haven’t shown a clear link between anticyclic citrullinated peptide titers and lung disease because those studies were limited to the proteins and peptides contained within conventional assays. This project will therefore look at a broader array of citrullinated proteins.
