A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes.
Standard
A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes. / Bryceson, Yenan T; Pende, Daniela; Maul-Pavicic, Andrea; Gilmour, Kimberly C; Ufheil, Heike; Vraetz, Thomas; Chiang, Samuel C; Marcenaro, Stefania; Meazza, Raffaella; Bondzio, Ilka; Walshe, Denise; Janka-Schaub, Gritta; Lehmberg, Kai; Beutel, Karin; Zur Stadt, Udo; Binder, Nadine; Arico, Maurizio; Moretta, Lorenzo; Henter, Jan-Inge; Ehl, Stephan.
in: BLOOD, Jahrgang 119, Nr. 12, 12, 2012, S. 2754-2763.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes.
AU - Bryceson, Yenan T
AU - Pende, Daniela
AU - Maul-Pavicic, Andrea
AU - Gilmour, Kimberly C
AU - Ufheil, Heike
AU - Vraetz, Thomas
AU - Chiang, Samuel C
AU - Marcenaro, Stefania
AU - Meazza, Raffaella
AU - Bondzio, Ilka
AU - Walshe, Denise
AU - Janka-Schaub, Gritta
AU - Lehmberg, Kai
AU - Beutel, Karin
AU - Zur Stadt, Udo
AU - Binder, Nadine
AU - Arico, Maurizio
AU - Moretta, Lorenzo
AU - Henter, Jan-Inge
AU - Ehl, Stephan
PY - 2012
Y1 - 2012
N2 - Familial hemophagocytic lymphohistiocytosis (FHL) is a life-threatening disorder of immune regulation caused by defects in lymphocyte cytotoxicity. Rapid differentiation of primary, genetic forms from secondary forms of hemophagocytic lymphohistiocytosis (HLH) is crucial for treatment decisions. We prospectively evaluated the performance of degranulation assays based on surface up-regulation of CD107a on natural killer (NK) cells and cytotoxic T lymphocytes in a cohort of 494 patients referred for evaluation for suspected HLH. Seventy-five of 77 patients (97%) with FHL3-5 and 11 of 13 patients (85%) with Griscelli syndrome type 2 or Chediak-Higashi syndrome had abnormal resting NK-cell degranulation. In contrast, NK-cell degranulation was normal in 14 of 16 patients (88%) with X-linked lymphoproliferative disease and in 8 of 14 patients (57%) with FHL2, who were identified by diminished intracellular SLAM-associated protein (SAP), X-linked inhibitor of apoptosis protein (XIAP), and perforin expression, respectively. Among 66 patients with a clinical diagnosis of secondary HLH, 13 of 59 (22%) had abnormal resting NK-cell degranulation, whereas 0 of 43 had abnormal degranulation using IL-2-activated NK cells. Active disease or immunosuppressive therapy did not impair the assay performance. Overall, resting NK-cell degranulation below 5% provided a 96% sensitivity for a genetic degranulation disorder and a specificity of 88%. Therefore, degranulation assays allow a rapid and reliable classification of patients, benefiting treatment decisions.
AB - Familial hemophagocytic lymphohistiocytosis (FHL) is a life-threatening disorder of immune regulation caused by defects in lymphocyte cytotoxicity. Rapid differentiation of primary, genetic forms from secondary forms of hemophagocytic lymphohistiocytosis (HLH) is crucial for treatment decisions. We prospectively evaluated the performance of degranulation assays based on surface up-regulation of CD107a on natural killer (NK) cells and cytotoxic T lymphocytes in a cohort of 494 patients referred for evaluation for suspected HLH. Seventy-five of 77 patients (97%) with FHL3-5 and 11 of 13 patients (85%) with Griscelli syndrome type 2 or Chediak-Higashi syndrome had abnormal resting NK-cell degranulation. In contrast, NK-cell degranulation was normal in 14 of 16 patients (88%) with X-linked lymphoproliferative disease and in 8 of 14 patients (57%) with FHL2, who were identified by diminished intracellular SLAM-associated protein (SAP), X-linked inhibitor of apoptosis protein (XIAP), and perforin expression, respectively. Among 66 patients with a clinical diagnosis of secondary HLH, 13 of 59 (22%) had abnormal resting NK-cell degranulation, whereas 0 of 43 had abnormal degranulation using IL-2-activated NK cells. Active disease or immunosuppressive therapy did not impair the assay performance. Overall, resting NK-cell degranulation below 5% provided a 96% sensitivity for a genetic degranulation disorder and a specificity of 88%. Therefore, degranulation assays allow a rapid and reliable classification of patients, benefiting treatment decisions.
KW - Humans
KW - Prospective Studies
KW - Sensitivity and Specificity
KW - Time Factors
KW - Killer Cells, Natural/physiology
KW - Cell Degranulation/physiology
KW - Immunologic Tests/methods
KW - Lymphohistiocytosis, Hemophagocytic/diagnosis/immunology/metabolism
KW - Lysosomal-Associated Membrane Protein 1
KW - T-Lymphocytes, Cytotoxic/physiology
KW - Humans
KW - Prospective Studies
KW - Sensitivity and Specificity
KW - Time Factors
KW - Killer Cells, Natural/physiology
KW - Cell Degranulation/physiology
KW - Immunologic Tests/methods
KW - Lymphohistiocytosis, Hemophagocytic/diagnosis/immunology/metabolism
KW - Lysosomal-Associated Membrane Protein 1
KW - T-Lymphocytes, Cytotoxic/physiology
M3 - SCORING: Journal article
VL - 119
SP - 2754
EP - 2763
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 12
M1 - 12
ER -
