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

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.