Circulating Fibrocytes as Biomarker of Prognosis in Hermansky-Pudlak Syndrome

Abstract

Rationale: The rate of progression of most interstitial lung diseases (ILD) is unpredictable. Fibrocytes are circulating bone marrow-derived cells that have been implicated in the pathogenesis of lung fibrosis. Hermansky-Pudlak syndrome (HPS), a genetic cause of ILD in early adulthood, allows for study of biomarkers of ILD in a homogeneous population at near-certain risk of developing fibrotic lung disease.Objectives: To test the hypothesis that, in subjects with HPS, the number or phenotype of circulating fibrocytes predicts progression and outcome of ILD.Methods: We measured circulating fibrocyte counts and chemokine levels in a cohort of subjects with HPS and healthy control subjects and correlated the results to disease outcome. Measurements and Main Results:In a cross-sectional analysis, peripheral blood fibrocyte concentrations were markedly elevated in a subset of subjects with HPS who had ILD but not subjects without lung disease or normal control subjects. The blood concentration of fibrocytes expressing the chemokine receptor CXCR4 correlated significantly with the plasma concentration of the CXCR4 ligand, CXCL12. In a longitudinal study, we found marked episodic elevations in circulating fibrocyte counts over a median follow-up period of 614 days. Elevations in both maximal values and final values of peripheral blood CXCR4 1 fibrocyte concentration were strongly associated with death from ILD. Conclusions: CXCR41 fibrocyte concentration may be useful as a biomarker for outcome of ILD in subjects with HPS.

Pulmonary Fibrosis in Hermansky-Pudlak Syndrome

“…In addition, patients with HPS-PF have been found to have increased numbers of circulating CXCR4-positive fibrocytes compared with subjects with HPS without lung disease or healthy control subjects (39). Increasingly, as suggested for IPF, studies point to the type II alveolar epithelial cell as central in the pathogenesis of HPS pulmonary fibrosis.…”

Circulating fibrocytes as biomarkers of impaired lung function in adults with sickle cell disease

“…15 They have been implicated in the pathogenesis of several interstitial lung diseases. [32][33][34] Previous data, largely on animal models, have suggested that fibrocytes are also involved in the pathogenesis of lung fibrosis in SCD. 17 Our previous data on patients show that circulating fibrocytes are increased and activated in patients with SCD compared with control participants; circulating fibrocytes also are increased further during VO crises.…”

Idiopathic pulmonary fibrosis biomarkers: clinical utility and a way of understanding disease pathogenesis

“…Since then, multiple studies have examined these cells, defined as expressing both the common leukocyte antigen CD45 and collagen I, when isolated from the peripheral blood 65 as biomarkers for disease severity in IPF and in other non-IPF diseases. [67][68][69][70] The fibrocyte bridges our categories of matrix and remodeling and immune dysregulation as it exhibits properties of both. "Bursts" of fibrocytes did not correlate with death in a study of Hermansky-Pudlak syndrome, 67 suggesting that deterioration or death does not correlate with absolute fibrocyte numbers and potentially limits enthusiasm for the fibrocyte as a biomarker.…”

“…[67][68][69][70] The fibrocyte bridges our categories of matrix and remodeling and immune dysregulation as it exhibits properties of both. "Bursts" of fibrocytes did not correlate with death in a study of Hermansky-Pudlak syndrome, 67 suggesting that deterioration or death does not correlate with absolute fibrocyte numbers and potentially limits enthusiasm for the fibrocyte as a biomarker. 71 Further study will be necessary to assess absolute numbers of fibrocytes, their behavior over time, and their relationship with pulmonary function.…”