Immune cells separate IPF, fibrotic hypersensitivity pneumonitis
Immune cell profiling shows rarer PF type had elevated cytotoxic T-cell levels
Researchers have identified immune cell populations that could be used to help distinguish fibrotic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis (IPF), a study suggests.
People with hypersensitivity pneumonitis, which is a rare type of pulmonary fibrosis (PF), show elevated levels of certain types of immune cells in the blood, namely T-cells. Both patient groups had elevations in immune cells called monocytes relative to healthy people.
“Both cell populations may guide the development of new biomarkers and therapeutic interventions,” the researchers wrote in the study, “Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitism,” which was published in the American Journal of Respiratory and Critical Care Medicine.
PF refers to a group of diseases marked by inflammation and scar tissue, or fibrosis, building up in the lungs. In IPF, the most common type, the exact cause of lung tissue scarring isn’t known. Fibrotic hypersensitivity pneumonitis is a rare type of PF caused by the lung’s immune response to inhaled particles like dust, mold, or other allergens. It can be acute, but is sometimes chronic and leads to irreversible fibrosis.
The immune system mechanisms that drive the condition aren’t fully understood and it can be difficult to distinguish hypersensitivity pneumonitis from IPF. Extensive inflammation and scarring feature in both, along with symptoms like shortness of breath and cough.
“Patients with these diseases can present very similarly,” Amy Zhao, a graduate student at Yale University and the study’s first author, said in a university news release. “They may have similar symptoms and radiographic imaging, so patients will sometimes have to undergo further workup using invasive biopsies, and therapeutic decisions may be delayed.”
Differences between two PF diseases
Here, Zhao and her colleagues looked for distinct immune cell profiles to help distinguish the two diseases.
The scientists genetically sequenced more than a half million immune cells from the bloodstream of patients with both diseases, along with people without PF, and found that people with fibrotic hypersensitivity pneumonitis had elevated levels of cytotoxic T-cells, which are immune cells involved in killing cancer cells, virus-infected cells, and other foreign cells. These cells carry a specialized type of enzyme, called granzymes, that lead to cell death.
Fibrotic hypersensitivity pneumonitis and IPF patients both had elevated levels of certain classes of monocytes, which are associated with lung fibrosis.
“These findings may be helpful in the future for guiding diagnosis,” Zhao said. “For example, if a patient has elevated levels of cytotoxic T-cells, it suggests more likely that they have fibrotic hypersensitivity pneumonitis over idiopathic pulmonary fibrosis, but of course, more studies are required.”
Treatment options for fibrotic hypersensitivity pneumonitis are limited. Current strategies rely on avoiding triggers and agents to suppress the immune system, but these are insufficient once fibrosis has started, according to Naftali Kaminski, MD, a Yale professor and the study’s senior author.
“By studying the immune system in these patients, we could develop novel targets that potentially limit the immune system from actively participating in lung scarring and fibrosis,” Kaminski said.
Cells were collected from people in the U.S. and Mexico. While the findings were similar between the groups, certain types of T-cell populations were observed only in Mexican patients.
“The fact that we found similar findings between the groups is very reassuring,” Kaminski said. “The fact that we also found findings specific to certain groups should encourage us to make sure that the populations we study are as diverse as possible.”
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