Abstract
T-cell clonality testing is integral to the diagnostic work-up of T-cell malignancies; however, current methods lack specificity and sensitivity, which can make the diagnostic process difficult. The recent discovery of a monoclonal antibody (mAb) specific for human TRBC1 will greatly improve the outlook for T-cell malignancy diagnostics. The anti-TRBC1 mAb can be used in flow cytometry immunophenotyping assays to provide a low-cost, robust, and highly specific test that detects clonality of immunophenotypically distinct T-cell populations. Recent studies demonstrate the clinical utility of this approach in several contexts; use of this antibody in appropriately designed flow cytometry panels improves detection of circulating disease in patients with cutaneous T-cell lymphoma, eliminates the need for molecular clonality testing in the context of large granular lymphocyte leukemia, and provides more conclusive results in the context of many other T-cell disorders. It is worth noting that the increased ability to detect discrete clonal T-cell populations means that identification of T-cell clones of uncertain clinical significance (T-CUS) will become more common. This review discusses this new antibody and describes how it defines clonal T-cells. We present and discuss assay design and summarize findings to date about the use of flow cytometry TRBC1 analysis in the field of diagnostics, including lymph node and fluid sample investigations. We also make suggestions about how to apply the assay results in clinical work-ups, including how to interpret and report findings of T-CUS. Finally, we highlight areas that we think will benefit from further research.
Highlights
Diagnosis of T-cell neoplasms relies on the close integration of clinical presentation and history with findings from histology and flow cytometry immunophenotyping of the relevant tissues
We describe how the anti-TRBC1 monoclonal antibody (mAb) may be included in laboratory assays, and we summarize the current knowledge-base with respect to flow cytometry-based analysis of TRCB1 during T-cell diagnostic work-up (Table 1)
In our extensive experience using TRBC1 within a single-tube comprehensive T-cell panel, we have found that T-cell neoplasms virtually always have distinct immunophenotypic features that largely separate them from background benign T-cells, but that this separation based on routine gating strategies is often imperfect and results in a very skewed rather than a purely unimodal TRBC1 expression pattern
Summary
Diagnosis of T-cell neoplasms relies on the close integration of clinical presentation and history with findings from histology and flow cytometry immunophenotyping of the relevant tissues. T-cell lymphoproliferations did not benefit from a readily available clonality assessment approach similar to the determination of immunoglobulin light chain restriction for B-cell lymphoproliferative disorders and required the deployment of less commonly utilized assays, such as killer immunoglobulin-like receptor (KIR) and Vβ T-cell receptor repertoire analysis [7,8,9,10,11]. These techniques have some limitations in being relatively expensive, labor-intensive, and requiring interpretive expertise that is not routinely available in all clinical laboratories. Rapid identification of immunophenotypically distinct T-cell clones, providing valuable information for the interpretation of limited specimens, and the need for additional work-up or an excisional biopsy
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