The cellular pathogenesis of paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria (PNH) is a unique disorder characteris ed by the triad of intravascular haemolysis, thrombosis and bone marrow fai lure. 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 sugges t that this is due to somatic cell selection, resulting from the presence i n the patient of autoreactive T cells that target glycosylphosphatidylinosi tol (GPI) in the context of an MHC-like molecule on the surface of haemopoi etic stem cells. PNH cells would escape damage precisely because they have lost most or all of their ability to produce GPI.