Whole transcriptome sequencing identifies increased CXCR2 expression in PNH granulocytes.
The aetiology of paroxysmal nocturnal haemoglobinuria (PNH) is a somatic mutation in the X-linked phosphatidylinositol glycan class A gene (PIGA), resulting in global deficiency of glycosyl phosphatidylinositol-anchored proteins (GPI-APs). This study applied RNA-sequencing to examine functional effects of the PIGA mutation in human granulocytes. CXCR2 expression was increased in GPI-AP-compared to GPI-AP+granulocytes. Macrophage migration inhibitory factor, a CXCR2 agonist, was significantly higher in plasma of PNH patients. Nuclear factor-κB phosphorylation was upregulated in GPI-AP-compared with GPI-AP+granulocytes. Our data suggest novel mechanisms in PNH, not obviously predicted by decreased production of the GPI moiety.
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Kohei
0000-0002-3423-1523
K
Hosokawa
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Sachiko
S
Kajigaya
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Keyvan
K
Keyvanfar
BGI-Shenzhen, Shenzhen, China.
Wangmin
W
Qiao
BGI-Shenzhen, Shenzhen, China.
Yanling
Y
Xie
Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD, USA.
Angelique
A
Biancotto
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Danielle M
DM
Townsley
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Xingmin
X
Feng
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Neal S
NS
Young
D015415:Biomarkers; D016022:Case-Control Studies; D016000:Cluster Analysis; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006098:Granulocytes / Q000378:metabolism*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D059467:Transcriptome
D015415:Biomarkers; D023063:Receptors, Interleukin-8B
CXCR2; RNA-sequencing; paroxysmal nocturnal haemoglobinuria