Thrombotic risk in paroxysmal nocturnal hemoglobinuria-like (PNH-like) phenotype

Abstract

The complement system is an essential component of the innate immune defence that, if overly activated, may damage organs and tissues. For this reason, there is a fine complement regulatory system. The complement modulation system includes two proteins with important regulatory activity, CD55 or decay accelerating factor (DAF) and CD59 or membrane inhibitor of reactive lysis (MIRL). The paroxysmal nocturnal hemoglobinuria (PNH) is a clonal and non-neoplastic disease characterized by intravascular haemolysis, occurrence of thrombosis and bone marrow failure. In clinical practice, in opposition to PNH, a variety of pathological conditions have been observed with an acquired and non-genetic deficiency of the regulatory proteins CD55 and CD59. This abnormal, non-clonal, reduced expression of complement regulatory proteins configures what we may define as PNH-like phenotype. Similarly to PNH, even in the PNH-like phenotype diseases there has been a greater exposure to the mediated complement cellular lysis and, a likely increased risk of thromboembolic events. Therefore, the knowledge of the potential roles of the complement system becomes necessary for a deeper understanding of several pathological conditions and for an improved clinical management of the patients.

Erythrocyte deformability profile evaluated by laser diffractometry in patients with multiple myeloma: Re-examination of our cases

“…It is well known that this defect is characterized by an altered synthesis of glycosylphosphatidylinositol, which is essential for the binding of some surface proteins, such as CD55 (decay accelerating factor or DAF) and CD59 (membrane inhibitor of reactive lysis or MIRL), to protect the red cells from intravascular lysis. Up to now, PNH-like clones have been also observed in different hematological diseases [46][47][48], but also in other clinical conditions [49,50] and in patients with rheumatic diseases [51, such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, vasculitis, dermatomyositis, ankylosing spondylitis, and mixed connective tissue diseases. In diabetes mellitus [52] it has been observed instead a decrease of the expression of CD55 and CD59 in endothelial cells incubated with high glucose concentration, normalized after co-incubation with verapamil.…”