Research ArticlePulmonary fibrosis

Peripheral Blood Mononuclear Cell Gene Expression Profiles Predict Poor Outcome in Idiopathic Pulmonary Fibrosis

Science Translational Medicine  02 Oct 2013:
Vol. 5, Issue 205, pp. 205ra136
DOI: 10.1126/scitranslmed.3005964

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Gene Signature Predicts Mortality

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that progresses at different rates. Although no therapies exist, giving patients a more accurate prognosis is highly desirable. To this end, Herazo-Maya and colleagues searched the genomes of cells circulating in the blood of IPF patients and found that four genes may be indicators of poor outcome.

Patients were recruited into discovery or replication cohorts from two different medical centers in the United States and followed until death or completion of the study. In both groups, genetic material was isolated from the patients’ peripheral blood mononuclear cells (PBMCs) and analyzed for increased or decreased expression. These gene expression profiles were then correlated with transplant-free survival (TFS). In the discovery cohort, Herazo-Maya et al. found that underexpression of the genes CD28, ICOS, LCK, and ITK was associated with decreased TFS. These findings were confirmed in the replication cohort. This “genomic model” incorporating the four genes was combined with the clinical outputs age, gender, and forced vital capacity to create an even stronger predictor of poor outcome. The authors suggest that the decreased expression of these genes might be linked to lower percentages of CD4+CD28+ T cells in the PBMC population, which could contribute to a mechanistic understanding of why some IPF patients progress differently than others.

The findings of this study have the potential to affect the care of patients with IPF as well as the understanding of disease mechanism. However, the combined genomic and clinical predictor will need to be validated in additional independent cohorts before translation.