Whole transcriptome sequencing identifies increased CXCR2 expression in PNH granulocytes

• Published in: British journal of haematology Vol. 177; no. 1; pp. 136 - 141
• Main Authors: Hosokawa, Kohei, Kajigaya, Sachiko, Keyvanfar, Keyvan, Qiao, Wangmin, Xie, Yanling, Biancotto, Angelique, Townsley, Danielle M., Feng, Xingmin, Young, Neal S.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2017
• Subjects: A gene; Biomarkers; Case-Control Studies; Cluster Analysis; CXCR2; CXCR2 protein; Flow Cytometry; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Glycosylphosphatidylinositol; Granulocytes; Granulocytes - metabolism; Hematology; Hemoglobinuria, Paroxysmal - genetics; High-Throughput Nucleotide Sequencing; Humans; Leukocyte migration; Leukocytes (granulocytic); Macrophage migration inhibitory factor; Macrophages; paroxysmal nocturnal haemoglobinuria; Phosphatidylinositol; Phosphorylation; Receptors, Interleukin-8B - genetics; Ribonucleic acid; RNA; RNA‐sequencing; Transcriptome; RNA-sequencing; paroxysmal nocturnal haemoglobinuria; CXCR2
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.14502

Summary 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.