Immune cell surge tied to inflammation and disease activity in active GPA
Higher Tph cell levels associated with ANCA and CRP markers
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People with active granulomatosis with polyangiitis (GPA), the most common type of ANCA-associated vasculitis (AAV), had significantly higher levels of a specific type of immune cell called peripheral helper T (Tph) cells in their blood, a study found.
Higher levels of circulating Tph (cTph) cells were also significantly linked to several markers of disease severity. The findings “may support a potential role in disease [development] and highlight their potential as therapeutic targets, warranting further investigation,” the researchers wrote.
The study, “Circulating peripheral helper T cells are expanded and associate with disease activity in granulomatosis with polyangiitis,” was published in Arthritis Research & Therapy.
How GPA and immune cells are connected
GPA is an autoimmune disease in which the immune system produces self-reactive antibodies called ANCAs. These antibodies attach to certain immune cells in the blood and can trigger inflammation in small blood vessels, leading to disease symptoms.
Antibodies, including ANCAs, are made by B-cells, a type of immune cell. Circulating Tph cells are another immune cell type that help activate B-cells, in part by releasing signaling molecules such as interleukin-21 (IL-21), which encourage B-cells to grow and produce antibodies.
Previous research has suggested that cTph cells may contribute to other antibody-driven autoimmune diseases. High levels of these cells have also been reported in people with microscopic polyangiitis (MPA), the second-most common AAV type, where they are linked to more active disease.
However, their role in GPA has not been well studied. To better understand this, scientists in the Netherlands set out to examine cTph cells in people with GPA.
Study examines Tph cell levels in active and remission GPA
The researchers measured the frequency and number of cTph cells in 100 people with GPA — 74 in remission and 26 with active disease at the time of testing — as well as in 22 age- and sex-matched healthy volunteers.
The proportion of memory cTph cells — which respond quickly when the immune system encounters a familiar threat — among CD4 helper T-cells was significantly higher in patients with active GPA compared with those in remission and healthy controls.
Overall, total memory cTph cell counts were significantly elevated in the active GPA group. Patients in remission had significantly lower counts than healthy controls — a difference the team wrote was “likely attributable to a decrease in total [helper T-cells] numbers, possibly due to the effects of immunosuppressive treatments.”
Additional analyses found changes in memory cTph cells that produced certain protein markers. Overall, these findings suggest that cTph cells in people with GPA tend to show an activated, pro-inflammatory profile that may enhance B-cell activity, supporting the idea that they could contribute to disease activity.
Among patients with active disease, higher numbers of memory cTph cells — particularly a subset known as cTph2 cells — were significantly associated with greater disease severity. This included higher blood levels of CRP, a marker of body-wide inflammation, and a higher Birmingham Vasculitis Activity Score.
Patients with higher levels of c-ANCAs, a type of ANCA commonly seen in GPA, had significantly higher counts of both memory cTph and cTph2 cells compared with those with lower c-ANCA levels.
Findings point to potential role in disease activity
Overall, the findings suggest that cTph cells “may play a critical role in sustaining systemic inflammation and driving B-cell activation, potentially contributing to ANCA production,” the scientists wrote.
The researchers noted that the study analyzed samples collected at a single point in time. They said longer-term studies are needed to determine how cTph cell levels change over time and how they relate to patient outcomes.
They also emphasized the need for more research to better understand how cTph cells may influence antibody production in GPA and other forms of AAV.
