T-cell clones of uncertain significance are highly prevalent and show close resemblance to T-cell large granular lymphocytic leukemia. Implications for laboratory diagnostics.
Min ShiHoratiu OlteanuDragan JevremovicRong HeDavid ViswanathaHeidi CorleyPedro HornaPublished in: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2020)
Benign clonal T-cell expansions in reactive immune responses often complicate the laboratory diagnosis T-cell neoplasia. We recently introduced a novel flow cytometry assay to detect T-cell clones in blood and bone marrow, based on the identification of a monophasic T-cell receptor (TCR) β chain constant region-1 (TRBC1) expression pattern within a phenotypically distinct TCRαβ T-cell subset. In routine laboratory practice, T-cell clones of uncertain significance (T-CUS) were detected in 42 of 159 (26%) patients without T-cell malignancy, and in 3 of 24 (13%) healthy donors. Their phenotype (CD8+/CD4-: 78%, CD4-/CD8-: 12%, CD4+/CD8+: 9%, or CD4+/CD8-: 2%) closely resembled that of 26 cases of T-cell large granular lymphocytic leukemia (T-LGLL) studied similarly, except for a much smaller clone size (p < 0.0001), slightly brighter CD2 and CD7, and slightly dimmer CD3 expression (p < 0.05). T-CUS was not associated with age, gender, comorbidities, or peripheral blood counts. TCR-Vβ repertoire analysis confirmed the clonality of T-CUS, and identified additional clonotypic CD8-positive subsets when combined with TRBC1 analysis. We hereby report the phenotypic features and incidence of clonal T-cell subsets in patients with no demonstrable T-cell neoplasia, providing a framework for the differential interpretation of T-cell clones based on their size and phenotypic properties.
Keyphrases
- peripheral blood
- bone marrow
- flow cytometry
- poor prognosis
- immune response
- regulatory t cells
- end stage renal disease
- high grade
- healthcare
- chronic kidney disease
- ejection fraction
- mesenchymal stem cells
- primary care
- binding protein
- risk factors
- high throughput
- peritoneal dialysis
- prognostic factors
- clinical practice
- toll like receptor
- patient reported outcomes
- high throughput sequencing
- health insurance
- patient reported