Biomarkers identify RA patients at risk of lung disease

An international team of researchers has identified biomarkers that may help pinpoint rheumatoid arthritis patients at risk of interstitial lung disease.

Dr. Juan Chen of the First Hospital of Xiamen (China) University and Dr. Tracy Doyle of Brigham and Women’s Hospital, Boston, classified Chinese rheumatoid arthritis (RA) patients into different clinical and radiographic stages of interstitial lung disease (ILD) – RA with no ILD, RA with mild ILD, and RA with advanced ILD (Arthritis Rheumatol. 2014 [doi:10.1002/art.38904]).

They used multiplex ELISA (enzyme-linked immunosorbent assay) to identify strong correlations between average serum levels of MMP-7 and IP10 and the grade of interstitial lung abnormalities. The average serum concentration of MMP-7 increased from 3.06 ng/mL in the RA patients with no ILD to 5.35 ng/mL in RA patients with ILD (P = .005). Levels of IP10 increased from 173.8 pg/mL in RA patients with no lung disease to 308.6 pg/mL in patients with ILD (P = .0004).

The researchers also found statistically significant elevations of both biomarkers in the patients with mild disease, “strengthening the apparent dose response relationship between these biomarkers and severity of radiographically defined interstitial lung abnormalities.”

Using a replication cohort from two academic centers in the United States, the researchers confirmed their findings by identifying statistically significant correlations between the two biomarkers and the presence of lung disease. The findings held strong even after adjustment for age, sex, smoking history, and 28-joint Disease Activity Score.

“[The results] demonstrate that elevated levels of IP10 and MMP-7 strongly correlate with the presence of RA-ILD, effectively supporting the hypothesis that RA-ILD represents a spectrum of pathology involving parenchymal lung inflammation and dysregulated tissue remodeling,” the study authors concluded.

Longitudinal studies are needed to determine the prognostic value of MMP-7 and IP10 in RA patients with clinically/radiographically established disease, “potentially enabling clinicians to distinguish those individuals most likely to develop progressive fibrosis and an IPF-like clinical course,” they added.

The research was supported in part by the Harvard KL2/Catalyst Medical Research Investigator Training Program as well as grants from the National Institutes of Health, Veterans Affairs Merit Review Program, and the *Rheumatology Research Foundation’s Within Our Reach program. No conflicts of interest were declared.

*Correction 10/30/2014: The article previously listed the Rheumatology Research Foundation under its old name, the American College of Rheumatology Research and Education Foundation.

An international team of researchers has identified biomarkers that may help pinpoint rheumatoid arthritis patients at risk of interstitial lung disease.

Dr. Juan Chen of the First Hospital of Xiamen (China) University and Dr. Tracy Doyle of Brigham and Women’s Hospital, Boston, classified Chinese rheumatoid arthritis (RA) patients into different clinical and radiographic stages of interstitial lung disease (ILD) – RA with no ILD, RA with mild ILD, and RA with advanced ILD (Arthritis Rheumatol. 2014 [doi:10.1002/art.38904]).

They used multiplex ELISA (enzyme-linked immunosorbent assay) to identify strong correlations between average serum levels of MMP-7 and IP10 and the grade of interstitial lung abnormalities. The average serum concentration of MMP-7 increased from 3.06 ng/mL in the RA patients with no ILD to 5.35 ng/mL in RA patients with ILD (P = .005). Levels of IP10 increased from 173.8 pg/mL in RA patients with no lung disease to 308.6 pg/mL in patients with ILD (P = .0004).

The researchers also found statistically significant elevations of both biomarkers in the patients with mild disease, “strengthening the apparent dose response relationship between these biomarkers and severity of radiographically defined interstitial lung abnormalities.”

Using a replication cohort from two academic centers in the United States, the researchers confirmed their findings by identifying statistically significant correlations between the two biomarkers and the presence of lung disease. The findings held strong even after adjustment for age, sex, smoking history, and 28-joint Disease Activity Score.

“[The results] demonstrate that elevated levels of IP10 and MMP-7 strongly correlate with the presence of RA-ILD, effectively supporting the hypothesis that RA-ILD represents a spectrum of pathology involving parenchymal lung inflammation and dysregulated tissue remodeling,” the study authors concluded.

Longitudinal studies are needed to determine the prognostic value of MMP-7 and IP10 in RA patients with clinically/radiographically established disease, “potentially enabling clinicians to distinguish those individuals most likely to develop progressive fibrosis and an IPF-like clinical course,” they added.

The research was supported in part by the Harvard KL2/Catalyst Medical Research Investigator Training Program as well as grants from the National Institutes of Health, Veterans Affairs Merit Review Program, and the *Rheumatology Research Foundation’s Within Our Reach program. No conflicts of interest were declared.

*Correction 10/30/2014: The article previously listed the Rheumatology Research Foundation under its old name, the American College of Rheumatology Research and Education Foundation.

An international team of researchers has identified biomarkers that may help pinpoint rheumatoid arthritis patients at risk of interstitial lung disease.

Dr. Juan Chen of the First Hospital of Xiamen (China) University and Dr. Tracy Doyle of Brigham and Women’s Hospital, Boston, classified Chinese rheumatoid arthritis (RA) patients into different clinical and radiographic stages of interstitial lung disease (ILD) – RA with no ILD, RA with mild ILD, and RA with advanced ILD (Arthritis Rheumatol. 2014 [doi:10.1002/art.38904]).

They used multiplex ELISA (enzyme-linked immunosorbent assay) to identify strong correlations between average serum levels of MMP-7 and IP10 and the grade of interstitial lung abnormalities. The average serum concentration of MMP-7 increased from 3.06 ng/mL in the RA patients with no ILD to 5.35 ng/mL in RA patients with ILD (P = .005). Levels of IP10 increased from 173.8 pg/mL in RA patients with no lung disease to 308.6 pg/mL in patients with ILD (P = .0004).

The researchers also found statistically significant elevations of both biomarkers in the patients with mild disease, “strengthening the apparent dose response relationship between these biomarkers and severity of radiographically defined interstitial lung abnormalities.”

Using a replication cohort from two academic centers in the United States, the researchers confirmed their findings by identifying statistically significant correlations between the two biomarkers and the presence of lung disease. The findings held strong even after adjustment for age, sex, smoking history, and 28-joint Disease Activity Score.

“[The results] demonstrate that elevated levels of IP10 and MMP-7 strongly correlate with the presence of RA-ILD, effectively supporting the hypothesis that RA-ILD represents a spectrum of pathology involving parenchymal lung inflammation and dysregulated tissue remodeling,” the study authors concluded.

Longitudinal studies are needed to determine the prognostic value of MMP-7 and IP10 in RA patients with clinically/radiographically established disease, “potentially enabling clinicians to distinguish those individuals most likely to develop progressive fibrosis and an IPF-like clinical course,” they added.

The research was supported in part by the Harvard KL2/Catalyst Medical Research Investigator Training Program as well as grants from the National Institutes of Health, Veterans Affairs Merit Review Program, and the *Rheumatology Research Foundation’s Within Our Reach program. No conflicts of interest were declared.

*Correction 10/30/2014: The article previously listed the Rheumatology Research Foundation under its old name, the American College of Rheumatology Research and Education Foundation.