Soluble IL-2R as a Marker of T Cell Activation in Immune-Mediated Diseases: Review and Case-Based Interpretation

The soluble interleukin-2 receptor (sIL-2R) is a novel biomarker associated with a variety of immune-mediated diseases. It is produced through the proteolytic cleavage of the membrane-bound interleukin-2 receptor α-chain on activated T lymphocytes; hence, its increase reflects T-cell activation and immune dysregulation. Elevated sIL-2R levels are frequently documented in conditions such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, histiocytosis, hemophagocytic lymphohistiocytosis, lymphomas, and graft-versus-host disease, suggesting a potential role in monitoring disease activity and progression. However, sIL-2R levels may increase in the context of immune response to infections and malignancies, requiring careful interpretation. It is essential to determine whether elevated levels of this marker within specific ranges could suggest a specific entity, due to the implications this may have for the management of patients. This case-based review presents five patients with different immune-mediated diseases, highlighting how these different conditions can present with characteristic ranges of sIL-2R elevation. By integrating clinical findings with sIL-2R measurements, we emphasize the biomarker’s utility in guiding diagnosis, as well as monitoring disease activity and determining prognosis, which can enhance clinical decision-making and patient management in rheumatology and related fields.