Complementopathies

Abstract

The complement system is an essential part of the innate immune system that requires careful regulation to ensure responses are appropriately directed against harmful pathogens, while preventing collateral damage to normal host cells and tissues. While deficiency in some components of the complement pathway is associated with increased susceptibility to certain infections, it has also become clear that inappropriate activation of complement is an important contributor to human disease. A number of hematologic disorders are driven by complement, and these disorders may be termed “complementopathies”. This includes paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), cold agglutinin disease (CAD) and other related disorders, which will be the focus of this review. A better understanding of the central role of the complement system in the pathophysiology of these disorders may allow for application of therapies directed at blocking the complement cascade.

The Complement System and Preeclampsia

“…Notably, in ex-vivo experiments, when the serum of women with HELLP syndrome and severe preeclampsia are mixed with cells lacking the GPI-anchored proteins CD55 and CD59, increased killing activity is seen compared to serum from healthy controls [75]. The magnitude of this cell killing activity is similar to the effect seen with aHUS serum, which is widely accepted as a complement-mediated disorder [76]. Ex-vivo, eculizumab reduces the killing effect on cells lacking the GPI proteins when serum from subjects with aHUS, HELLP and preeclampsia is used.…”

Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial

“…2,9,12 The predominant mechanism of erythrocyte breakdown, known as extravascular hemolysis, is phagocytosis of cells opsonized with complement protein C3b, generated by the classical pathway. 2,[13][14][15] Essential clinical manifestations are anemia and, in up to 90% of the patients, cold-induced acrocyanosis and/or Raynaud phenomena. 10 Although most literature emphasizes the importance of avoiding cold exposure, descriptive studies have shown that 70% to 80% of unselected patients have received pharmacologic treatment.…”

How I manage patients with cold agglutinin disease

“…Today, CAD is considered a well‐defined clinico‐pathological entity (Randen et al , ; Berentsen, ; Baines & Brodsky, ; Jaeger, ). It should be distinguished from secondary CA syndrome (CAS), a similar but still more uncommon cold haemolytic syndrome complicating a distinct underlying clinical disease (Berentsen et al , ).…”