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Circulating Fibrocytes as Biomarkers of Disease Activity Among Patients with Connective Tissue Disease-Associated Interstitial Lung Disease and Interstitial Pneumonitis with Autoimmune Features
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A1680 - Circulating Fibrocytes as Biomarkers of Disease Activity Among Patients with Connective Tissue Disease-Associated Interstitial Lung Disease and Interstitial Pneumonitis with Autoimmune Features
Author Block: J. Odackal1, V. Yu2, M. D. Burdick2, B. Mehrad3; 1Department of Medicine, University of Virginia, Charlottesville, VA, United States, 2University of Virginia, Charlottesville, VA, United States, 3Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Gainesville, FL, United States.
RATIONALE: Interstitial lung disease complicating connective tissue disease (CTD-ILD) and interstitial pneumonitis with autoimmune features (IPAF) are characterized by heterogeneous radiographic and histologic patterns and variable response to immunosuppressive therapy, resulting in an unpredictable course. Biomarkers of disease activity and responsiveness to therapy would therefore be of clinical value. Fibrocytes are a population of bone marrow-derived circulating progenitor cells that home to sites of tissue injury and contribute to fibrosis. Prior studies have shown that episodic elevations in circulating fibrocytes were strongly predictive of death in other forms of diffuse parenchymal lung diseases. To our knowledge, the utility of circulating fibrocytes in autoimmune ILDs has not been studied previously. HYPOTHESIS: In patients with autoimmune interstitial lung disease, the concentration and/or activation state of circulating fibrocytes predict the clinical course in autoimmune interstitial lung diseases. METHODS: We recruited 50 subjects between 2011-2015. Connective tissue disease diagnoses were verified based on American College of Rheumatology criteria and IPAF based on consensus criteria. We collected longitudinal serial clinical assessments, pulmonary function tests, and measurements of circulating fibrocytes. RESULTS: The median age of subjects was 60 (interquartile range 50-69) and 29 were women. 18 had IPAF, 13 had anti-synthetase syndrome or myositis-associated ILD, 11 had scleroderma, 5 had rheumatoid arthritis, and 3 had mixed connective tissue disease. Median FVC was 62% predicted (51%-78%) and DLCO was 43% predicted (26%-56%). UIP diagnosis, based on HRCT appearance or imaging, was present in 11. Subjects had a median of 5 visits (3-7) over 1118 days (685-1464). During this time, all but 7 were treated with immunosuppressive medications, 5 experienced PFT deterioration, and 15 died. Initial fibrocyte counts was 9.88e5 cell/ml (3.04e5-1.46e6), significantly higher than matched healthy controls. Fibrocyte counts varied markedly during follow-up. Elevated fibrocyte counts were associated with death or deterioration of PFTs.
CONCLUSIONS: Fibrocytes may represent a novel biomarker in autoimmune interstitial lung diseases.
Author Block: J. Odackal1, V. Yu2, M. D. Burdick2, B. Mehrad3; 1Department of Medicine, University of Virginia, Charlottesville, VA, United States, 2University of Virginia, Charlottesville, VA, United States, 3Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Gainesville, FL, United States.
RATIONALE: Interstitial lung disease complicating connective tissue disease (CTD-ILD) and interstitial pneumonitis with autoimmune features (IPAF) are characterized by heterogeneous radiographic and histologic patterns and variable response to immunosuppressive therapy, resulting in an unpredictable course. Biomarkers of disease activity and responsiveness to therapy would therefore be of clinical value. Fibrocytes are a population of bone marrow-derived circulating progenitor cells that home to sites of tissue injury and contribute to fibrosis. Prior studies have shown that episodic elevations in circulating fibrocytes were strongly predictive of death in other forms of diffuse parenchymal lung diseases. To our knowledge, the utility of circulating fibrocytes in autoimmune ILDs has not been studied previously. HYPOTHESIS: In patients with autoimmune interstitial lung disease, the concentration and/or activation state of circulating fibrocytes predict the clinical course in autoimmune interstitial lung diseases. METHODS: We recruited 50 subjects between 2011-2015. Connective tissue disease diagnoses were verified based on American College of Rheumatology criteria and IPAF based on consensus criteria. We collected longitudinal serial clinical assessments, pulmonary function tests, and measurements of circulating fibrocytes. RESULTS: The median age of subjects was 60 (interquartile range 50-69) and 29 were women. 18 had IPAF, 13 had anti-synthetase syndrome or myositis-associated ILD, 11 had scleroderma, 5 had rheumatoid arthritis, and 3 had mixed connective tissue disease. Median FVC was 62% predicted (51%-78%) and DLCO was 43% predicted (26%-56%). UIP diagnosis, based on HRCT appearance or imaging, was present in 11. Subjects had a median of 5 visits (3-7) over 1118 days (685-1464). During this time, all but 7 were treated with immunosuppressive medications, 5 experienced PFT deterioration, and 15 died. Initial fibrocyte counts was 9.88e5 cell/ml (3.04e5-1.46e6), significantly higher than matched healthy controls. Fibrocyte counts varied markedly during follow-up. Elevated fibrocyte counts were associated with death or deterioration of PFTs.
CONCLUSIONS: Fibrocytes may represent a novel biomarker in autoimmune interstitial lung diseases.
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