Utilizing T-Cell Assays in Diagnosing Familial Hemophagocytic Lymphohistiocytosis and Defects in Lymphocyte Exocytosis

According to a prospective analysis recently published in Blood, the combined analysis of T-cell receptor-triggered cytotoxic T lymphocyte and Fc receptor-triggered NK-cell exocytosis demonstrated efficacy for the diagnosis of patients with suspected familial hemophagocytic lymphohistiocytosis (HLH) or atypical manifestations of congenital defects in lymphocyte exocytosis.

“Primary hemophagocytic lymphohistiocytosis is a life-threatening disorder associated with autosomal recessive variants in genes required for perforin-mediated lymphocyte cytotoxicity. A rapid diagnosis is crucial for successful treatment,” stated lead study author Samuel C.C. Chiang, PhD, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, and colleagues.

“Although defective cytotoxic T lymphocyte (CTL) function causes pathogenesis, quantification of natural killer (NK) cell exocytosis triggered by K562 target cells currently represents a standard diagnostic procedure for primary HLH,” they added.

Investigators evaluated different lymphocyte exocytosis assays among 213 patients who were referred for evaluation for suspected hemophagocytic lymphohistiocytosis and related hyperinflammatory syndromes. In total, 138 patients received a molecular diagnosis consistent with primary hemophagocytic lymphohistiocytosis.

Results demonstrated that, compared to routine K562 cell-based assays, the assessment of Fc receptor-triggered NK-cell and T-cell receptor-triggered cytotoxic T lymphocyte exocytosis displayed higher sensitivity and improved specificity for the diagnosis of primary hemophagocytic lymphohistiocytosis. Combined, these assays provided a sensitivity of 100% and specificity of 98.3%. By comparison, NK-cell exocytosis after K562 target cell stimulation displayed a higher inter-individual variability.

“We thus recommend combined analysis of T[-]cell receptor-triggered CTL and Fc receptor-triggered NK-cell exocytosis for the diagnosis of patients with suspected familial HLH or atypical manifestations of congenital defects in lymphocyte exocytosis,” concluded Dr. Chiang and colleagues.

Source:

Chiang S, Covill L, Tesi B, et al. Efficacy of T cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis. Blood. Published online July 3, 2024. doi: 10.1182/blood.2024024499