Increased anergic B cells and decreased antibody‐secreting cells during romiplostim treatment in patients with immune thrombocytopenia

Summary Patients with immune thrombocytopenia (ITP) exhibit substantial heterogeneity in treatment responses. Approximately 30%–50% of patients maintain remission after discontinuation of thrombopoietin receptor agonists (TPO‐RA), suggesting immunomodulatory effects beyond enhanced thrombopoiesis. However, predictive or explanatory biomarkers for sustained remission after TPO‐RA are currently lacking. In this study, we performed spectral flow cytometry on B cells of longitudinal samples from patients before, during and after treatment with the TPO‐RA romiplostim. We observed that anergic B cells were the predominant B cell population within the peripheral blood in romiplostim‐naïve patients (mean: 51.7%) and in healthy controls (mean: 47.8%). Paired longitudinal analyses showed a significant increase in anergic B cells during romiplostim treatment, with values exceeding those of healthy controls after 1 year of treatment (mean: 58.4%, p = 0.006). After tapering, the anergic B cells remained stably increased (mean: 59.7%), both in treatment‐free patients as well as patients who restarted romiplostim. Within the switched‐ and antibody‐secreting cell (ASC) compartment, a decrease of immunoglobulin G (IgG + ) and immunoglobulin A (IgA + ) ASC was observed during romiplostim ( p = 0.04 and p = 0.08). These results reveal a previously unappreciated potential role for anergic B cells and ASCs in ITP and emphasize the need for further investigations of TPO‐RA‐induced B cell responses in ITP.