IPF causes progressive scarring
of the lungs, leading to cough, shortness of breath, and potentially
death. In most cases, the cause cannot be identified, and there is no
cure other than a lung transplant. While some patients experience a
progressive course that leads to death within one to two years, others
experience a relative stable disease.
The researchers’ goal was to
identify changes in expression of genes in the blood that are
predictive of poor outcomes among patients with IPF.
Using two
cohorts of patients, the researchers from Yale, University of Chicago,
and University of Pittsburgh analyzed the expression of the genes in the
whole genome of patients with IPF, and identified 52 genes that
significantly correlated with outcome. They further found that the
decreased expression of four genes — CD28, ICOS, LCK, and ITK —
predicted shorter survival time in patients with IPF.
The research
team believes discovery of these biomarkers will help physicians better
predict disease presence, severity, and prognosis in IPF patients.
“Given the fact that lung transplantation is the only therapy that has
shown to improve survival in IPF, our test could allow physicians to
refer IPF patients for lung transplant at the right time — not too late
and not too early,” said senior and corresponding author Dr. Naftali
Kaminski, professor and chief of pulmonary, critical care, and sleep
medicine at Yale School of Medicine.
Right now, at least six drugs are being studied for IPF. First author Jose Herazo-Maya of Yale School of Medicine said that one of the study’s major impacts would be on drug studies. “Current drug studies do not address the variability in outcomes of IPF patients,” he said. “Our findings may help investigators target patients who are more likely to progress and improve.”
The
decreased genes that predicted shorter survival time were mostly
related to immune activation. Author Imre Noth, leader of the University
of Chicago team, said, “Our result may also shed light on disease
mechanisms, by supporting the emerging notion that aberrant immunity may
play a role in IPF.”
Other authors are Brenda Juan-Guardela of
Yale; Yong Huang, Rekha Vij, Yves Lussier, and Joe Garcia of the
University of Chicago; and Steven Duncan, SunHwan Kim, George Tseng,
Eleanor Feingold, Thomas Richards, Kathleen Lindell, Jianmin Xue, Kevin
Gibson, and Steven Shapiro of the University of Pittsburgh.
This
study was supported by grants from the National Heart, Lung, and Blood
Institute (HL0894932, HL108642, HL095397, HL073241, HL107172, HL101740,
HL080513), the Dorothy P. and Richard P. Simmons Endowed Chair for
Pulmonary Research, the Pulmonary Fibrosis Foundation, and the Coalition
for Pulmonary Fibrosis.
Source: Yale University
