Scientists spot potential new markers for treating chronic ITP
Immune cell changes may offer fresh clues to long-lasting condition
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Researchers in Turkey have uncovered changes in immune cells and surface proteins on platelets, which are tiny, colorless cell fragments in the blood that help form clots, that may contribute to the development of chronic immune thrombocytopenia (ITP) — so-called when symptoms of the autoimmune disease are long-lasting.
Such changes could eventually serve as biomarkers to monitor disease activity and predict how patients respond to treatment, according to the scientists. The team noted that “the potential use of [one] parameter … could be particularly valuable for monitoring the effectiveness of immunosuppressive therapies and predicting long-term outcomes.”
Still, the researchers stressed that larger studies “are needed to clarify the mechanistic and clinical significance of these findings.”
The study, “Flow cytometric analysis of T-cell subsets and platelet surface markers in patients with immune thrombocytopenia: a case-control study,” was published in the journal Annals of Hematology.
ITP occurs when the immune system mistakenly attacks and destroys platelets faster than the body can replace them. This makes it harder for blood to clot, increasing the risk of bruising and bleeding. Clinicians call it chronic ITP when the condition lasts for 12 months or longer.
Focusing on T-cells and platelets
While B-cells — immune cells that produce antibodies, including the self-reactive antibodies that target clot-promoting platelets in ITP — are known to play a central role in the disease, scientists increasingly recognize that T-cells may also contribute to platelet destruction. T-cells are a type of white blood cell that help coordinate the body’s immune response.
Previous studies suggest this may happen because of an imbalance between T-cells that activate immune responses and regulatory T-cells, which normally help keep those responses in check and prevent the immune system from attacking the body’s own tissues.
Several proteins found on the surface of platelets, including CD41, CD42, and CD61 — all frequent targets of the self-reactive antibodies that drive ITP — are commonly used to assess platelet function, the researchers noted. As such, changes in these proteins may therefore reflect the extent of platelet damage and disease activity.
“Despite significant progress in understanding ITP pathogenesis [disease development], the precise mechanisms underlying immune dysregulation remain incompletely understood,” the researchers wrote. “Furthermore, there is a need for better biomarkers to predict treatment response and disease course.”
To address these gaps, researchers from Mersin University collected blood samples from 26 adults with chronic ITP, as well as 25 healthy volunteers, all followed at their center between November 2022 and October 2023. The goal was to evaluate T-cell subpopulations and levels of key platelet surface proteins to identify potential biomarkers of disease activity.
Discoveries could help in monitoring chronic ITP
As expected, people with ITP were found to have far fewer platelets than healthy volunteers. Their platelets were also larger on average, suggesting the body was trying to replace platelets being destroyed more quickly than normal, according to the researchers.
When the team examined T-cells, they found that the overall proportions of the major T-cell populations were similar between people with ITP and healthy volunteers. But differences were seen in specific markers of T-cell maturation and activation, the researchers noted.
For example, the ratio between CD45RA-positive T-cells and CD4-positive T-cells (CD45RA+/CD4+ ratio) was significantly lower in people with ITP. According to the researchers, such a finding “is consistent with chronic immune activation and ongoing autoimmune processes in ITP patients.”
Significant differences were also found in platelet surface proteins. Levels of both CD41 and CD61 were significantly lower in people with ITP than in healthy volunteers, whereas CD42 levels were similar in both groups.
When the researchers grouped patients according to platelet counts, however, they found that levels of CD41, CD42, and CD61 were all significantly lower in those with fewer than 30,000 platelets per microliter of blood.
“The correlation between platelet count and CD41, CD42, and CD61 [levels] supports the concept that platelet surface glycoprotein expression serves as a marker of disease severity and platelet turnover,” the researchers wrote.
The … parameters we identified … may serve as biomarkers for disease monitoring and treatment response assessment.
The team also found a higher ratio of CD62L-negative T-cells to platelets in people with ITP. According to the researchers, “the loss of CD62L … is associated with T-cell activation and differentiation into effector cells.” An increased ratio may indicate increased interactions between activated T-cells and platelets, “supporting the emerging concept of T-cell-mediated platelet destruction in ITP,” the team noted.
The results also showed that patients whose disease was in remission or who had responded well to treatment tended to have a higher CD25+/CD4+ ratio, supporting its use “as a treatment response marker,” the researchers wrote.
Overall, according to the scientists, “the … parameters we identified … may serve as biomarkers for disease monitoring and treatment response assessment.”
Still, the team noted that, “although these findings may contribute to understanding ITP [immune mechanisms], the absence of functional immune analyses limits mechanistic interpretation.” Given this, “further longitudinal and functional studies are needed to validate these markers and clarify their potential clinical utility as biomarkers or therapeutic targets,” the researchers concluded.
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