Paroxysmal Nocturnal Hemoglobinuria (PNH): From Basic Research to Clinical Points of View

Name: Kriangsak Pakdeesuwan

Organization : Mahldol University. Faculty of Science. Department of Biochemistry and Siriraj Hospital. Department of Medicine. Division of Hematology

Name: Prapon Wilairat

Organization : Mahldol University. Faculty of Science. Department of Biochemistry

Name: Wanchai Wanachiwanawin

Organization : Siriraj Hospital. Department of Medicine. Division of Hematology

keyword: Complex pathophysiolgy

MeSH: Hemoglobinuria, Paroxysmal

; Glycosyl-phosphatidylinositol-anchor deficiency

; Heterogeneous cellular phenotypes

; Paroxysmal nocturnal hemoglobinuria

; PIG-A somatic mutation

Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder characterized by chronic intravascular hemolysis resulting from unusual susceptibility to complement among a discrete population of abnormal erythrocytes. Absence from their surfaces of complement regulatory proteins, such as CD59 and decay-accelerating factor (DAF), is responsible for the hypersensitivity to complement of the abnormal cells. DAF, CD59 and also some other membrane proteins are inserted to the cell surface via a glycosylphosphatidylinositol (GPI) moiety. The deficiency of such proteins from the surface membrane is caused by an impaired synthesis of GPI anchor in the affected cells. Studies with abnormal lymphoid cell lines established from patients with PNH indicated that the first step of GPI-anchor synthesis is defective. Recently, the genes responsible for this particular step (PIG-A, PIG-H and PIG-C) have been cloned and characterized. Somatic mutation of only X-linked PIG-A has been shown to be responsible for over 1 00 patients with PNH studied to date. The explanation for the uniformity of the responsible gene is that only PIG-A is haploid with respect to the X chromosome even in female due to the inactivation by Iyonization. In contrast, all other genes essential for GPI-anchor assembly are autosomal which require two inactivation mutations on both alleles to gain GPI-deficient phenotype. Thus, the molecular pathogenesis underlying intravascular hemolysis of PNH has been virtually clarified. Next major concern is to explain how PIG-A somatic mutation determines the heterogeneity of clinical manifestations and cellular phenotypes as observed in some patients.

Mahidol University

Address: NAKHONPATHOM

Email: liwww@mahidol.ac.th

Created: 2013

Modified: 2016-11-18

Issued: 1997-01/06

บทความ/Article

application/pdf

Mahidol Journal. 4, 1 (Jan.-June 1997) 29-34

eng

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