TY - JOUR
T1 - NK cytotoxicity mediated by CD16 but not by NKp30 is functional in Griscelli syndrome
AU - Gazit, Roi
AU - Aker, Memet
AU - Elboim, Moran
AU - Achdout, Hagit
AU - Katz, Gil
AU - Wolf, Dana G.
AU - Katzav, Shulamit
AU - Mandelboim, Ofer
N1 - Funding Information:
Grant information: This research was supported by Ministry of Research, Technology and Higher Education Republic of Indonesia through Master of Education Towards Doctoral Scholarship Program for Excellence Undergraduate and the support through World Class Professor Program Scheme-B No. 123.57/D2.3/KP/2018.
Funding Information:
This research was supported by Ministry of Research, Technology and Higher Education Republic of Indonesia through Master of Education Towards Doctoral Scholarship Program for Excellence Undergraduate and the support through World Class Professor Program Scheme-B No. 123.57/D2.3/KP/2018.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - Griscelli syndrome (GS) type 2 is an autosomal recessive disorder represented by pigment dilution and impaired cytotoxic T lymphocyte (CTL) activity. NK activity has been scarcely investigated in GS patients. Here, we describe a new patient, possessing a hemophagocytic syndrome with a homozygous Q118X nonsense RAB27Amutation. Single specific primer-polymerase chain reaction (SSP-PCR) was developed based on this mutation and is currently used in prenatal genetic analysis. As expected, CTLs in the patient are not functional and NK cytotoxicity against K562 or 721.221 cells is diminished. Surprisingly, however, we demonstrate that CD16-mediated killing is intact in this patient and is therefore RAB27A independent, whereas NKp30-mediated killing is impaired and is therefore RAB27A dependent. We further analyzed the signaling pathways of these 2 receptors and demonstrated phosphorylation of Vav1 after CD16 activation but not after NKp30 engagement. Thus, we identify a novel homozygous mutation in the RAB27A gene of a new GS patient, observe for the first time that some activating NK receptors function in GS patients, and demonstrate a functional dichotomy in the killing mediated by these human NK-activating receptors.
AB - Griscelli syndrome (GS) type 2 is an autosomal recessive disorder represented by pigment dilution and impaired cytotoxic T lymphocyte (CTL) activity. NK activity has been scarcely investigated in GS patients. Here, we describe a new patient, possessing a hemophagocytic syndrome with a homozygous Q118X nonsense RAB27Amutation. Single specific primer-polymerase chain reaction (SSP-PCR) was developed based on this mutation and is currently used in prenatal genetic analysis. As expected, CTLs in the patient are not functional and NK cytotoxicity against K562 or 721.221 cells is diminished. Surprisingly, however, we demonstrate that CD16-mediated killing is intact in this patient and is therefore RAB27A independent, whereas NKp30-mediated killing is impaired and is therefore RAB27A dependent. We further analyzed the signaling pathways of these 2 receptors and demonstrated phosphorylation of Vav1 after CD16 activation but not after NKp30 engagement. Thus, we identify a novel homozygous mutation in the RAB27A gene of a new GS patient, observe for the first time that some activating NK receptors function in GS patients, and demonstrate a functional dichotomy in the killing mediated by these human NK-activating receptors.
UR - http://www.scopus.com/inward/record.url?scp=34248370215&partnerID=8YFLogxK
U2 - 10.1182/blood-2006-09-047159
DO - 10.1182/blood-2006-09-047159
M3 - Article
AN - SCOPUS:34248370215
SN - 0006-4971
VL - 109
SP - 4306
EP - 4312
JO - Blood
JF - Blood
IS - 10
ER -