Study lays groundwork for understanding RA-ILD/RA-IPF overlap

Comparative serum protein biomarker profiling may allow researchers to identify patients with rheumatoid arthritis-associated interstitial lung disease and/or idiopathic pulmonary fibrosis, according to findings published in Arthritis Rheumatology.

“The real question we wanted to answer was whether we could find a molecular profile that explains the clinical overlap between advanced RA-ILD and IPF,” Dana P. Ascherman, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh School of Medicine, told Healio Pulmonology. “Based on this, the ultimate goal is to develop a biomarker signature that might elucidate critical disease-related pathways and identify the subset of RA patients with ILD who will do poorly.”

The researchers profiled 45 serum protein biomarkers, including cytokines/chemokines, growth factors and matrix metalloproteinases, in two cohorts of patients with rheumatoid arthritis (RA), one a Veterans Affairs group and one consisting of patients recruited through non-VA academic medical centers. The VA group included 17 patients with no ILD and 86 with ILD, whereas the non-VA cohort included 22 patients with no ILD and 49 with ILD. There were also 100 patients with IPF and 38 healthy controls enrolled in this study. Ascherman noted a high prevalence of smoking and male predominance in the VA cohort, which may have affected study findings.

In fact, results adjusted for age, sex, smoking and articular disease activity showed that a number of markers — including eotaxin, growth-related oncogene (GRO-1), macrophage inflammatory protein-1 beta (MIP1-beta), interleukin-8 (IL-8) and several matrix metalloproteinases — differentiated ILD from no ILD in the VA cohort of patients with RA. A number of mediators also distinguished patients with RA with and without ILD in the non-VA cohort. However, apart from MIP1-beta, results showed “little overlap” in protein signatures between the two RA-ILD cohorts, according to Ascherman.

“This was a little bit of a surprise,” Ascherman said. “There were actually big differences between the two cohorts of RA patients with ILD.”

In turn, the degree of overlap between RA-ILD and IPF was quite different between the VA and non-VA cohorts, suggesting that background demographic features, including male gender and smoking history, exert a critical effect on peripheral blood biomarker signatures.

Although these cross-sectional analyses have seemingly identified serum protein biomarker profiles of RA-ILD, longitudinal studies will ultimately be required to determine if the observed biomarkers will be predictive of disease progression and poor prognosis in these and other cohorts of patients with RA.

“I do think we have defined relevant biomarker signatures in RA-ILD,” Ascherman said. “However, these signatures depend on underlying factors — such as age, sex and smoking prevalence — that likely differ between specific patient populations.” – by Rob Volansky

Disclosure: Ascherman reports no relevant financial disclosures.

Comparative serum protein biomarker profiling may allow researchers to identify patients with rheumatoid arthritis-associated interstitial lung disease and/or idiopathic pulmonary fibrosis, according to findings published in Arthritis Rheumatology.

“The real question we wanted to answer was whether we could find a molecular profile that explains the clinical overlap between advanced RA-ILD and IPF,” Dana P. Ascherman, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh School of Medicine, told Healio Pulmonology. “Based on this, the ultimate goal is to develop a biomarker signature that might elucidate critical disease-related pathways and identify the subset of RA patients with ILD who will do poorly.”

The researchers profiled 45 serum protein biomarkers, including cytokines/chemokines, growth factors and matrix metalloproteinases, in two cohorts of patients with rheumatoid arthritis (RA), one a Veterans Affairs group and one consisting of patients recruited through non-VA academic medical centers. The VA group included 17 patients with no ILD and 86 with ILD, whereas the non-VA cohort included 22 patients with no ILD and 49 with ILD. There were also 100 patients with IPF and 38 healthy controls enrolled in this study. Ascherman noted a high prevalence of smoking and male predominance in the VA cohort, which may have affected study findings.

In fact, results adjusted for age, sex, smoking and articular disease activity showed that a number of markers — including eotaxin, growth-related oncogene (GRO-1), macrophage inflammatory protein-1 beta (MIP1-beta), interleukin-8 (IL-8) and several matrix metalloproteinases — differentiated ILD from no ILD in the VA cohort of patients with RA. A number of mediators also distinguished patients with RA with and without ILD in the non-VA cohort. However, apart from MIP1-beta, results showed “little overlap” in protein signatures between the two RA-ILD cohorts, according to Ascherman.

“This was a little bit of a surprise,” Ascherman said. “There were actually big differences between the two cohorts of RA patients with ILD.”

In turn, the degree of overlap between RA-ILD and IPF was quite different between the VA and non-VA cohorts, suggesting that background demographic features, including male gender and smoking history, exert a critical effect on peripheral blood biomarker signatures.

Although these cross-sectional analyses have seemingly identified serum protein biomarker profiles of RA-ILD, longitudinal studies will ultimately be required to determine if the observed biomarkers will be predictive of disease progression and poor prognosis in these and other cohorts of patients with RA.

PAGE BREAK

“I do think we have defined relevant biomarker signatures in RA-ILD,” Ascherman said. “However, these signatures depend on underlying factors — such as age, sex and smoking prevalence — that likely differ between specific patient populations.” – by Rob Volansky

Disclosure: Ascherman reports no relevant financial disclosures.