Predicting Survival Trajectories in IPF Using 2 T-Cell Biomarkers

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Analysis of ICOS and CD28 from the first blood draw identified 3 populations of patients with IPF at high, intermediate, and low risk for all-cause mortality.
Analysis of ICOS and CD28 from the first blood draw identified 3 populations of patients with IPF at high, intermediate, and low risk for all-cause mortality.

Assessment of 2 T-cell biomarkers, inducible costimulator (ICOS) and CD28, predicts survival trajectories in patients with idiopathic pulmonary fibrosis (IPF), according to research presented at the American Thoracic Society (ATS) 2017 International Conference, held May 19-24 in Washington, DC.1

Catherine A. Bonham, MD, instructor of medicine at the University of Chicago, Illinois, and colleagues collected data from a prospective, longitudinal study from 59 patients with IPF and 22 age-matched control individuals. Clinical, blood, and pulmonary function test data were used to analyze cell surface expression of CD45RO, CD28, ICOS, and PD-1 on CD4 T cells by means of flow cytometry. Patients were followed until study end, transplant, or death.

 

Dr Bonham and colleagues found there was a significant associated with declining forced vital capacity and diffusing capacity of the lung for carbon monoxide with ICOS and CD28 on CD4 T cells. This finding was independent of age, sex, race, smoking history, or immunosuppressant use.

In analyzing the ICOS and CD28 from the first blood draw, researchers were able to stratify 3 distinct survival trajectories for patients with IPF: high risk, intermediate risk, and low risk.

  • High risk: Patients in the lower quintile of CD28 expression had poor survival.
  • Intermediate risk: Patients with low ICOS but high CD28 had intermediate survival rates.
  • Low risk: Patients in the highest quintile of ICOS expression on CD4 T cells at study entry had markedly improved survival.

No change in PD-1 expression was found. However, "lungs and thoracic lymph nodes from IPF patients yielded markedly high ICOS in comparison to controls, even though ICOS in IPF blood was low," noted the researchers.

"This suggests IPF memory T cells are highly activated," said Dr Bonham in a press release.2 "The T cells within the lungs appear as though they are ready to fight, but we don't know yet what they are reacting to, or even if this response is appropriate."

More studies need to be done to learn about the mechanism of ICOS and CD28 before drugs targeting these molecules can be used as treatment for IPF, but the findings from this study provide "a useful tool for clinicians and researchers faced with predicting which IPF patients are at risk of early death and in need of aggressive management strategies," concluded the researchers.

Reference

  1. Bonham C, Hrusch CL, Manns S, et al. Stratification of idiopathic pulmonary fibrosis survival by ICOS and CD28 surface expression on T cells. Presented at: American Thoracic Society (ATS) 2017 International Conference; Washington, DC; May 19-24. Abstract 10988.
  2. Two biomarkers appear to predict course of IPF [press release]. New York, NY: American Thoracic Society. http://www.thoracic.org/about/newsroom/press-releases/conference/2017/bonham-and-ipf-and-t-cells.php Published May 21, 2017. Accessed May 22, 2017.