Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis

Chiang S. C. C., Covill L. E., Tesi B., Campbell T. M., Schlums H., Nejati-Zendegani J., ...Daha Fazla

Blood, cilt.144, sa.8, ss.873-887, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 144 Sayı: 8
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1182/blood.2024024499
  • Dergi Adı: Blood
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
  • Sayfa Sayıları: ss.873-887
  • Erciyes Üniversitesi Adresli: Evet

Özet

Primary hemophagocytic lymphohistiocytosis (HLH) 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. 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. We have prospectively evaluated different lymphocyte exocytosis assays in 213 patients referred for evaluation for suspected HLH and related hyperinflammatory syndromes. A total of 138 patients received a molecular diagnosis consistent with primary HLH. Assessment of Fc receptor–triggered NK-cell and T-cell receptor (TCR)–triggered CTL exocytosis displayed higher sensitivity and improved specificity for the diagnosis of primary HLH than routine K562 cell–based assays, with these assays combined providing a sensitivity of 100% and specificity of 98.3%. By comparison, NK-cell exocytosis after K562 target cell stimulation displayed a higher interindividual variability, in part explained by differences in NK-cell differentiation or large functional reductions after shipment. We thus recommend combined analysis of TCR-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.