Researchers have identified a potential diagnostic biomarker for primary immune thrombocytopenia (ITP), according to a study published in British Journal of Haematology.
“There is still no specific diagnostic test for ITP, thus it remains a disease of exclusion,” explained study author Lamya Garabet, MD, PhD, of the Center for Laboratory Medicine at Østfold Hospital in Grålum, Norway. “The lack of a definitive diagnostic test results in inaccurate diagnosis and unnecessary treatment, which may expose patients to potentially harmful side effects.”
According to Dr. Garabet, identifying a reliable diagnostic biomarker for ITP “would facilitate accurate diagnosis, ensuring appropriate treatment for the right patients while preventing misdiagnosis as ITP of other thrombocytopenic disorders.”
Dr. Garabet and colleagues studied 12 microRNAs (miRNAs) identified in previous studies of ITP: miR-199a-5p, miR-33a-5p, miR-195-5p, miR-130a-3p, miR-144-3p, miR-146a-5p, miR-222-3p, miR-374b-5p, miR-486-5p, miR-1341-5p, miR-766-3p, and miR-409-3p. These miRNAs were evaluated in two cohorts of 61 patients with ITP (one cohort with newly diagnosed or persistent ITP and one with patients at different disease stages) and 28 healthy controls.
“Circulating miRNAs in the blood are easily accessible, and their stability under various physicochemical conditions makes them promising noninvasive biomarkers for disease diagnosis and prognosis,” Dr. Garabet said.
“Studies have explored miRNAs in the T cells, platelets, exosomes, and plasma of patients with ITP to understand the disease’s underlying pathophysiology and assess their diagnostic potential. However, variability in different factors, including patient populations, sample materials, and methodological differences in miRNA measurement has led to inconsistencies and challenges in reproducing findings across studies,” she said. “Consequently, validating previously identified miRNAs as biomarkers is essential.”
The analysis identified five miRNAs that were expressed differentially in patients with ITP compared with healthy controls: miR-199a-5p, miR-33a-5p, miR-374b-5p, miR-146a-5, and miR-409-3p. However, of the five identified, only miR-199a-5p was differentially expressed and downregulated in all of the patients with ITP, suggesting potential as a diagnostic biomarker for ITP.
Among patients with newly diagnosed ITP, miR-199a-5p and miR-374b-5p also had good discriminative ability between patients with ITP and healthy controls.
“miR-199a-5p has been shown to inhibit the production of interleukin 6 and tumor necrosis factor-α and suppresses the transforming growth factor-β signaling pathway, promoting a proinflammatory immune response, thus the downregulation of miR-199a-5p may play a crucial role in the pathophysiology of ITP,” Dr. Garabet said. “Therefore, identification of miR-199a-5p as a biomarker in ITP is of great importance.”
Circulating miRNAs can be measured using polymerase chain reaction (PCR), a technique available in most laboratories, according to Dr. Garabet.
“In our study, we measured this miRNA using droplet digital PCR (ddPCR), which enables absolute quantification of miRNAs. Laboratories can make the measurement of this miRNA available for physicians to request in regular blood samples,” Dr. Garabet said. “The ddPCR method is relatively easy to perform and provides results within a short timeframe, making it a feasible option for clinical application.”
The researchers’ findings should be considered with one important limitation in mind. In this analysis, miR-199a-5p was analyzed in plasma, “meaning its exact cellular source remains uncertain,” Dr. Garabet noted. As such, the lower expression of miR-199a-5p could be directly linked to ITP or be a consequence of low platelet counts.
“However, measurement of other platelet-abundant miRNAs did not correlate with the platelet count, suggesting that the decrease in miRNA expression was not solely due to reduced platelet numbers,” Dr. Garabet explained.
More studies are needed to confirm these results, both in patients with newly diagnosed ITP and in those with nonimmune thrombocytopenia, including chemotherapy-induced thrombocytopenia and hereditary thrombocytopenia.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Garabet L, Rangberg A, Eriksson AM, et al. MicroRNA-199a-5p may be a diagnostic biomarker of primary ITP [published online ahead of print, 2025 Jan. 7]. Br J Haematol. doi: 10.1111/bjh.19987.
