Regulatory T-cell Subsets Can Help ID Active AAV, New Study Finds
Tregs found to distinguish patients with active disease, in remission
Patients with active ANCA-associated vasculitis (AAV) can be distinguished from those who are in remission by the presence of different subsets of a type of immune cell known as regulatory T-cells, or Tregs, a new study reported.
Reduced functionality of these regulatory immune cells had been previously implicated in AAV. But researchers hadn’t yet determined if certain subsets were particularly involved.
“This is the first study identifying associations between the frequency of specific subsets of Tregs and their possible implications in disease activity and organ involvement in ANCA vasculitis,” the researchers wrote.
“The findings of this study will help set the foundation for the development of tailored Treg-based therapies for ANCA vasculitis,” they wrote.
The study, “The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis,” was published in the journal Clinical & Translational Immunology.
The role of Tregs in AAV
Tregs are a class of immune cells that help to prevent excessive, self-harmful immune responses in the body. They do this by regulating the activity of other types of immune cells that drive inflammation.
Dysregulation of Tregs has been reported in a number of autoimmune diseases, including AAV, where these cells have a reduced capacity to suppress other components of the immune system.
There are several different types of Tregs, each of which may play a unique role in autoimmunity. Yet, it remains unclear which subsets might be specifically involved in AAV.
“To exploit Tregs as a biomarker and therapeutic approach in ANCA vasculitis, a strong foundation and understanding of Treg heterogeneity and their implications in disease manifestation is imperative,” the researchers wrote.
To address this knowledge gap, a team at the University of North Carolina at Chapel Hill examined the different Treg subtypes present in the blood of AAV patients compared with healthy people.
Results showed that AAV patients had more Tregs than healthy people. This increase was largely driven by a subset of patients in remission, who had significant elevations in Tregs compared with both healthy controls and AAV patients with active disease.
“An expansion of partially functional Tregs could compensate for their decreased overall function and be sufficient to induce remission in patients,” the researchers offered as an explanation for these findings.
Tregs also were significantly increased in the subset of patients who had been treated with rituximab or prednisone at the time of blood collection, or six months earlier, compared with patients who didn’t receive the medications. Rituximab is also sometimes used to prevent relapses in AAV patients.
A certain variant in the FOXP3 gene that resides on Tregs has been previously associated with their diminished suppressive capacity in autoimmune disease. This variant causes a protein-coding section, called exon 2, to be missing.
AAV patients and healthy controls had similar numbers of exon 2-lacking cells, regardless of disease activity. Further analysis revealed that these cells were not conventional Tregs, and the mutation is “unlikely the driver of Tregs’ impaired suppressive capacity in ANCA vasculitis,” the researchers wrote.
But other Treg subtypes did appear to be linked to active disease. Specifically, a subset of Tregs that expressed the CCR7 protein were observed at higher levels in patients with AAV compared with healthy people.
Moreover, these CCR7-positive cells and another type, called CD103-positive cells, were each at higher levels in patients with active disease than in those who were in remission or didn’t have AAV.
In contrast, a subset of CXCR3-expressing Tregs were found at lower levels among those with active disease, particularly in patients with kidney involvement.
Fewer CXCR3-positive cells was also associated with a higher disease activity, as measured by BVAS, a measure that is “heavily influenced by renal involvement.”
Looking at all three of these Treg subsets together offered the best predictive power for identifying patients with active disease versus those who were in remission or those who had no AAV than any single subtype alone.
Overall, “changes in the frequency of Treg subsets could potentially contribute to the diminished suppressive capacity of total Tregs reported in ANCA vasculitis, specifically during active disease,” the researchers wrote.
Researchers noted that it remains unclear how these populations of Tregs might change over time, adding that the actual suppressive capacity of each subtype wasn’t measured. The effects of immunosuppressive therapies on these T-cells will also need to be further explored.
Still, “Treg heterogeneity has the potential to become a biomarker of disease activity,” the researchers wrote, noting that the findings could form the basis of the development of new Treg-targeted treatments.