The cellular pathogenesis of paroxysmal nocturnal haemoglobinuria.
Paroxysmal nocturnal haemoglobinuria (PNH) is a unique disorder characterised by the triad of intravascular haemolysis, thrombosis and bone marrow failure. In the early seventies it was shown that PNH is a clonal disease; and in the nineties the molecular basis of the PNH abnormality was elucidated. However, what makes a PNH clone expand is still not known. Here, we suggest that this is due to somatic cell selection, resulting from the presence in the patient of autoreactive T cells that target glycosylphosphatidylinositol (GPI) in the context of an MHC-like molecule on the surface of haemopoietic stem cells. PNH cells would escape damage precisely because they have lost most or all of their ability to produce GPI.
Karadimitris
A
A
Luzzatto
L
L
D006457:Hemoglobinuria, Paroxysmal / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans