Paroxysmal nocturnal haemoglobinuria (PNH): novel therapies for an ancient disease

Summary In the UK, early work on paroxysmal nocturnal haemoglobinuria (PNH) was conducted by John Dacie who, at the Hammersmith Hospital, first hypothesised that the PNH abnormality might arise through a somatic mutation; and who outlined with S.M. Lewis the relationship between PNH and aplastic ana...

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Bibliographic Details
Published in:British journal of haematology 2020-11, Vol.191 (4), p.579-586
Main Authors: Luzzatto, Lucio, Karadimitris, Anastasios
Format: Article
Language:English
Subjects:
clonal disease
complement blockade
Complement component C3
Complement component C5
Hematology
immune escape
inherited PIG genes mutations
Mutation
paroxysmal nocturnal haemoglobinuria
Patients
Pharmacokinetics
Phosphatidylinositol
Phosphatidylinositol N-acetylglucosaminyltransferase
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Summary:Summary In the UK, early work on paroxysmal nocturnal haemoglobinuria (PNH) was conducted by John Dacie who, at the Hammersmith Hospital, first hypothesised that the PNH abnormality might arise through a somatic mutation; and who outlined with S.M. Lewis the relationship between PNH and aplastic anaemia. When the phosphatidylinositol glycan anchor biosynthesis Class A (PIGA) gene was identified by Taroh Kinoshita’s group, jointly with him the Hammersmith group proved that PNH is caused in most patients by a single somatic mutation in the PIGA gene. At the same time, after Bruno Rotoli had spent a sabbatical at the Hammersmith, the ‘immune escape model’ for the pathogenesis of PNH was developed. Early this century, Peter Hillmen, formerly at the Hammersmith and now in Leeds, spearheaded the use of the complement‐blocking (anti‐C5) antibody eculizumab. This new medicine radically changed the management and the clinical course of patients with PNH. Recently a derivative of eculizumab with more favourable pharmacokinetics has been introduced. In view of the fact that these agents are associated with C3‐dependent extravascular haemolysis, it is important that a number of inhibitors of the proximal complement pathway are now in the offing and may further improve the life of patients with PNH.
ISSN:0007-1048
1365-2141
DOI:10.1111/bjh.17147