Paroxysmal nocturnal hemoglobinuria and the age of therapeutic complement inhibition

References

• Brodsky RA. Narrative review: paroxysmal nocturnal hemoglobinuria: the physiology of complement-related hemolytic anemia. Ann. Intern. Med. 148(8), 587–595 (2008).
   PubMed Web of Science ®Google Scholar
• Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood 113(26), 6522–6527 (2009).
   PubMed Web of Science ®Google Scholar
• Parker CJ. Historical aspects of paroxysmal nocturnal haemoglobinuria: 'defining the disease'. Br. J. Haematol. 117(1), 3–22 (2002).
   PubMed Web of Science ®Google Scholar
• Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 333(19), 1253–1258 (1995).
   PubMed Web of Science ®Google Scholar
• Moyo VM, Mukhina GL, Garrett ES, Brodsky RA. Natural history of paroxysmal nocturnal hemoglobinuria using modern diagnostic assays. Br. J. Haematol. 126(1), 133–138 (2004).
   PubMed Web of Science ®Google Scholar
• de Latour RP, Mary JY, Salanoubat C et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood 112(8), 3099–3106 (2008).
   PubMed Web of Science ®Google Scholar
• Miyata T, Takeda J, Iida Y et al. The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science 259, 1318–1320 (1993).
   PubMed Web of Science ®Google Scholar
• Bessler M, Mason PJ, Hillmen P et al. Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. EMBO J. 13(1), 110–117 (1994).
   PubMed Web of Science ®Google Scholar
• Medof ME, Kinoshita T, Nussenzweig V. Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. J. Exp. Med. 160(5), 1558–1578 (1984).
   PubMed Web of Science ®Google Scholar
• Rollins SA, Sims PJ. The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b-9. J. Immunol. 144(9), 3478–3483 (1990).
   PubMed Web of Science ®Google Scholar
• Walport MJ. Complement. First of two parts. N. Engl. J. Med. 344(14), 1058–1066 (2001).
   PubMed Web of Science ®Google Scholar
• Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 293(13), 1653–1662 (2005).
   PubMed Web of Science ®Google Scholar
• Risitano AM, Notaro R, Marando L et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood 113(17), 4094–4100 (2009).
   PubMed Web of Science ®Google Scholar
• Hochsmann B, Leichtle R, von Zabern I, Kaiser S, Flegel WA, Schrezenmeier H. Paroxysmal nocturnal haemoglobinuria treatment with eculizumab is associated with a positive direct antiglobulin test. Vox Sang. 102(2), 159–166 (2012).
   Google Scholar
• Nishimura J, Kanakura Y, Ware RE et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine (Baltimore) 83(3), 193–207 (2004).
   Google Scholar
• Antin JH, Ginsburg D, Smith BR, Nathan DG, Orkin SH, Rappeport JM. Bone marrow transplantation for paroxysmal nocturnal hemoglobinuria: eradication of the PNH clone and documentation of complete lymphohematopoietic engraftment. Blood 66(6), 1247–1250 (1985).
   Google Scholar
• Suenaga K, Kanda Y, Niiya H et al. Successful application of nonmyeloablative transplantation for paroxysmal nocturnal hemoglobinuria. Exp. Hematol. 29(5), 639–642 (2001).
   Google Scholar
• Santarone S, Bacigalupo A, Risitano AM et al. Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Haematologica 95(6), 983–988 (2010).
   PubMed Web of Science ®Google Scholar
• Brodsky RA, Luznik L, Bolanos-Meade J, Leffell MS, Jones RJ, Fuchs EJ. Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. Bone Marrow Transplant. 42(8), 523–527 (2008).
   PubMed Web of Science ®Google Scholar
• Hillmen P, Hall C, Marsh JC et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 350(6), 552–559 (2004).
   PubMed Web of Science ®Google Scholar
• Hillmen P, Young NS, Schubert J et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 355(12), 1233–1243 (2006).
   PubMed Web of Science ®Google Scholar
• Brodsky RA, Young NS, Antonioli E et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood 111(4), 1840–1847 (2008).
   PubMed Web of Science ®Google Scholar
• Kinoshita T, Inoue N. Dissecting and manipulating the pathway for glycosylphos-phatidylinositol-anchor biosynthesis. Curr. Opin. Chem. Biol. 4(6), 632–638 (2000).
   Google Scholar
• Low MG, Saltiel AR. Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science 239(4837), 268–275 (1988).
   Google Scholar
• Rosse WF. Paroxysmal nocturnal hemoglobinuria as a molecular disease [Review]. Medicine 76(2), 63–93 (1997).
   Google Scholar
• Takahaski M, Takeda J, Hirose S et al. Deficient biosynthesis of N-Acetylglucosaminyl-phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with paroxysmal nocturnal hemoglobinuria. J. Exp. Med. 177(2), 517–521 (1993).
   Google Scholar
• Takeda J, Miyata T, Kawagoe K et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell 73(4), 703–711 (1993).
   PubMed Web of Science ®Google Scholar
• Miyata T, Yamada N, Iida Y et al. Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 330(4), 249–255 (1994).
   PubMed Web of Science ®Google Scholar
• Oni SB, Osunkoya BO, Luzzatto L. Paroxysmal nocturnal hemoglobinuria: evidence for monoclonal origin of abnormal red cells. Blood 36(2), 145–152 (1970).
   PubMed Web of Science ®Google Scholar
• Hu R, Mukhina GL, Piantadosi S, Barber JP, Jones RJ, Brodsky RA. PIG-A mutations in normal hematopoiesis. Blood 105(10), 3848–3854 (2005).
   PubMed Web of Science ®Google Scholar
• Nagarajan S, Brodsky R, Young NS, Medof ME. Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia. Blood 86(12), 4656–4661 (1995).
   PubMed Web of Science ®Google Scholar
• Araten DJ, Nafa K, Pakdeesuwan K, Luzzatto L. Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc. Natl Acad. Sci. USA 96(9), 5209–5214 (1999).
   PubMed Web of Science ®Google Scholar
• Pu JJ, Hu R, Mukhina GL, Carraway HE, McDevitt MA, Brodsky RA. The small population of PIG-A mutant cells in myelodysplastic syndromes do not arise from multipotent hematopoietic stem cells. Haematologica 97(8), 1225–1233 (2012).
   Google Scholar
• Luzzatto L, Bessler M, Rotoli B. Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell 88(1), 1–4 (1997).
   PubMed Web of Science ®Google Scholar
• Hanaoka N, Kawaguchi T, Horikawa K, Nagakura S, Mitsuya H, Nakakuma H. Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP. Blood 107(3), 1184–1191 (2006).
   PubMed Web of Science ®Google Scholar
• Savage WJ, Barber JP, Mukhina GL et al. Glycosylphosphatidylinositol-anchored protein deficiency confers resistance to apoptosis in PNH. Exp. Hematol. 37(1), 42–51 (2009).
   Google Scholar
• Rus H, Cudrici C, Niculescu F. The role of the complement system in innate immunity. Immunol.Res. 33(2), 103–112 (2005).
   PubMed Web of Science ®Google Scholar
• Lublin DM, Atkinson JP. Decay-accelerating factor: biochemistry, molecular biology, and function. Ann. Rev. Immunol. 7, 35–58 (1989).
   PubMed Web of Science ®Google Scholar
• Holguin MH, Fredrick LR, Bernshaw NJ, Wilcox LA, Parker CJ. Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria. J. Clin. Invest. 84(1), 7–17 (1989).
   PubMedGoogle Scholar
• Risitano AM, Notaro R, Marando L et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood 113(17), 4094–4100 (2009).
   PubMed Web of Science ®Google Scholar
• Wiedmer T, Hall SE, Ortel TL, Kane WH, Rosse WF, Sims PJ. Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria. Blood 82(4), 1192–1196 (1993).
   Google Scholar
• Hugel B, Socie G, Vu T et al. Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. Blood 93(10), 3451–3456 (1999).
   PubMed Web of Science ®Google Scholar
• Liebman HA, Feinstein DI. Thrombosis in patients with paroxysmal noctural hemoglobinuria is associated with markedly elevated plasma levels of leukocyte-derived tissue factor. Thromb. Res. 111(4–5), 235–238 (2003).
   Google Scholar
• Simak J, Holada K, Risitano AM, Zivny JH, Young NS, Vostal JG. Elevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria. Br. J. Haematol. 125(6), 804–813 (2004).
   Google Scholar
• Helley D, de Latour RP, Porcher R et al. Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Haematologica 95(4), 574–581 (2010).
   PubMedGoogle Scholar
• Hall SE, Rosse WF. The use of monoclonal antibodies and flow cytometry in the diagnosis of paroxysmal nocturnal hemoglobinuria. Blood 87(12), 5332–5340 (1996).
   PubMed Web of Science ®Google Scholar
• Brodsky RA, Mukhina GL, Li S et al. Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin. Am. J. Clin. Pathol. 114(3), 459–466 (2000).
   PubMed Web of Science ®Google Scholar
• Borowitz MJ, Craig FE, DiGiuseppe JA et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin. Cytom. 78(4), 211–230 (2010).
   PubMedGoogle Scholar
• Parker C, Omine M, Richards S et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 106(12), 3699–3709 (2005).
   PubMed Web of Science ®Google Scholar
• Mukhina GL, Buckley JT, Barber JP, Jones RJ, Brodsky RA. Multilineage glycosylphosphatidylinositol anchor deficient hematopoiesis in untreated aplastic anemia. Br. J. Haematol. 115(2), 476–482 (2001).
   PubMed Web of Science ®Google Scholar
• Ritis K, Doumas M, Mastellos D et al. A novel C5a receptor-tissue factor cross-talk in neutrophils links innate immunity to coagulation pathways. J. Immunol. 177(7), 4794–4802 (2006).
   PubMed Web of Science ®Google Scholar
• Saso R, Marsh J, Cevreska L et al. Bone marrow transplants for paroxysmal nocturnal haemoglobinuria. Br. J. Haematol. 104(2), 392–396 (1999).
   PubMed Web of Science ®Google Scholar
• Takahashi Y, McCoy JP Jr, Carvallo C et al. In vitro and in vivo evidence of PNH cell sensitivity to immune attack after nonmyeloablative allogeneic hematopoietic cell transplantation. Blood 103(4), 1383–1390 (2004).
   PubMed Web of Science ®Google Scholar
• Brodsky RA. Stem cell transplantation for paroxysmal nocturnal hemoglobinuria. Haematologica 95(6), 855–856 (2010).
   PubMed Web of Science ®Google Scholar
• Peffault de LR, Schrezenmeier H, Bacigalupo A et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica 97(11), 1666–1673 (2012).
   Google Scholar
• Rosse WF. Treatment of paroxysmal nocturnal hemoglobinuria. Blood 60(1), 20–23 (1982).
   Google Scholar
• Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood 102(10), 3587–3591 (2003).
   PubMed Web of Science ®Google Scholar
• Lee JW, Jang JH, Kim JS et al. Clinical signs and symptoms associated with increased risk for thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry. Int. J. Hematol. 97(6), 749–757 (2013).
   PubMed Web of Science ®Google Scholar
• Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat. Biotechnol. 25(11), 1256–1264 (2007).
   PubMed Web of Science ®Google Scholar
• Wang Y, Rollins SA, Madri JA, Matis LA. Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and ameliorates established disease. Proc. Natl Acad. Sci. USA 92(19), 8955–8959 (1995).
   PubMed Web of Science ®Google Scholar
• Hill A, Hillmen P, Richards SJ et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood 106(7), 2559–2565 (2005).
   PubMed Web of Science ®Google Scholar
• Hillmen P, Muus P, Roth A et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br. J. Haematol. 162(1), 62–73 (2013).
   PubMed Web of Science ®Google Scholar
• Hillmen P, Muus P, Roth A et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br. J. Haematol. 162(1), 62–73 (2013).
   PubMed Web of Science ®Google Scholar
• Hillmen P, Muus P, Duhrsen U et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 110(12), 4123–4128 (2007).
   PubMed Web of Science ®Google Scholar
• Hill A, Rother RP, Arnold L et al. Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization. Haematologica 95(4), 567–573 (2010).
   PubMed Web of Science ®Google Scholar
• Kelly RJ, Hill A, Arnold LM et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 117(25), 6786–6792 (2011).
   PubMed Web of Science ®Google Scholar
• Dezern AE, Dorr D, Brodsky RA. Predictors of hemoglobin response to eculizumab therapy in paroxysmal nocturnal hemoglobinuria. Eur. J. Haematol. 90(1), 16–24 (2013).
   PubMed Web of Science ®Google Scholar
• Weitz IC, Razavi P, Rochanda L et al. Eculizumab therapy results in rapid and sustained decreases in markers of thrombin generation and inflammation in patients with PNH independent of its effects on hemolysis and microparticle formation. Thromb. Res. 130(3), 361–368 (2012).
   PubMed Web of Science ®Google Scholar
• Fridkis-Hareli M, Storek M, Mazsaroff I et al. Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of the human complement alternative pathway-mediated diseases. Blood 118(17), 4705–4713 (2011).
   PubMed Web of Science ®Google Scholar
• Risitano AM, Notaro R, Pascariello C et al. The complement receptor 2/factor H fusion protein TT30 protects paroxysmal nocturnal hemoglobinuria erythrocytes from complement-mediated hemolysis and C3 fragment. Blood 119(26), 6307–6316 (2012).
   PubMed Web of Science ®Google Scholar