336
Views
40
CrossRef citations to date
0
Altmetric
Reviews

Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape

, , , &

References

  • 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 1993;73(4):703-11
  • Miyata T, Takeda J, Iida Y, et al. The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science 1993;259(5099):1318-20
  • Luzzatto L, Bessler M, Rotoli B. Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell 1997;88(1):1-4
  • Krawitz PM, Hochsmann B, Murakami Y, et al. A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT. Blood 2013;122(7):1312-15
  • Karadimitris A, Manavalan JS, Thaler HT, et al. Abnormal T-cell repertoire is consistent with immune process underlying the pathogenesis of paroxysmal nocturnal hemoglobinuria. Blood 2000;96(7):2613-20
  • Risitano AM. Paroxysmal nocturnal hemoglobinuria and the complement system: recent insights and novel anticomplement strategies. Adv Exp Med Biol 2013;735:155-72
  • Risitano AM. Paroxysmal nocturnal hemoglobinuria and other complement-mediated hematological disorders. Immunobiology 2012;217(11):1080-7
  • Medof ME, Gottlieb A, Kinoshita T, et al. Relationship between decay accelerating factor deficiency, diminished acetylcholinesterase activity, and defective terminal complement pathway restriction in paroxysmal nocturnal hemoglobinuria erythrocytes. J Clin Invest 1987;80(1):165-74
  • Risitano AM. Anti-Complement Treatment in Paroxysmal Nocturnal Hemoglobinuria: where we Stand and Where we are Going. Transl Med UniSa 2014;8:43-52
  • Rotoli B, Luzzatto L. Paroxysmal nocturnal haemoglobinuria. Baillieres Clin Haematol 1989;2(1):113-38
  • Risitano AM, Rotoli B. Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents. Biologics 2008;2(2):205-22
  • Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol 2007;137(3):181-92
  • Inoue N, Murakami Y, Kinoshita T. Molecular genetics of paroxysmal nocturnal hemoglobinuria. Int J Hematol 2003;77(2):107-12
  • 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 1999;96(9):5209-14
  • Jasinski M, Keller P, Fujiwara Y, et al. GATA1-Cre mediates Piga gene inactivation in the erythroid/megakaryocytic lineage and leads to circulating red cells with a partial deficiency in glycosyl phosphatidylinositol-linked proteins (paroxysmal nocturnal hemoglobinuria type II cells). Blood 2001;98(7):2248-55
  • Araten DJ, Bessler M, McKenzie S, et al. Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones. Leukemia 2002;16(11):2243-8
  • Inoue N, Izui-Sarumar T, Murakami Y, et al. Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). Blood 2006;108(13):4232-6
  • Shen W, Makishima H, Clemente M, et al. Hierarchical clonal architecture. in paroxysmal nocturnal hemoglobinuria: stepwise acquisition of mutations. J Clin Invest 2014. In press
  • Young NS, Maciejewski JP. Genetic and environmental effects in paroxysmal nocturnal hemoglobinuria: this little PIG-A goes “Why? Why? Why?”. J Clin Invest 2000;106(5):637-41
  • Gargiulo L, Lastraioli S, Cerruti G, et al. Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria. Blood 2007;109(11):5036-42
  • Gargiulo L, Papaioannou M, Sica M, et al. Glycosylphosphatidylinositol-specific, CD1d-restricted T cells in paroxysmal nocturnal hemoglobinuria. Blood 2013;121(14):2753-61
  • Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005;106(12):3699-709
  • Luzzatto L, Gianfaldoni G, Notaro R. Management of paroxysmal nocturnal haemoglobinuria: a personal view. Br J Haematol 2011;153(6):709-20
  • Luzzatto L, Risitano AM, Notaro R. Paroxysmal nocturnal hemoglobinuria and eculizumab. Haematologica 2010;95(4):523-6
  • Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 2013;121(25):4985-96
  • Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995;333(19):1253-8
  • Socie G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet 1996;348(9027):573-7
  • de Latour RP, Mary JY, Salanoubat C, et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood 2008;112(8):3099-106
  • Moyo VM, Mukhina GL, Garrett ES, Brodsky RA. Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol 2004;126(1):133-8
  • Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood 2003;102(10):3587-91
  • Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006;355(12):1233-43
  • 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 2008;111(4):1840-7
  • Hillmen P, Muus P, Duhrsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007;110(12):4123-8
  • Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 2011;117(25):6786-92
  • Nishimura J, Yamamoto M, Hayashi S, et al. Genetic variants in C5 and poor response to eculizumab. N Engl J Med 2014;370(7):632-9
  • Rondelli T, Risitano AM, Peffault de Latour R, et al. Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria. Haematologica 2014;99(2):262-6
  • 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 2009;113(17):4094-100
  • 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 2010;95(4):567-73
  • Ricklin D, Lin Z, Schmidt CQ, et al. Towards a model of complement-mediated extravascular hemolysis of red blood cells in PNH patients under standard treatment: implications for novel therapeutic options. Presented at 11th International Conference on Innate Immunity, Aegean Conferences; Aldemar Olympian Village, Olympia, Greece; 2014
  • Peffault de Latour R, Schrezenmeier H, Bacigalupo A, et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica 2012;97(11):1666-73
  • Brodsky RA, Luznik L, Bolanos-Meade J, et al. Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. Bone Marrow Transplant 2008;42(8):523-7
  • Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood 2009;113(26):6522-7
  • Risitano AM, Notaro R, Luzzatto L, et al. Paroxysmal nocturnal hemoglobinuria – hemolysis before and after eculizumab. N Engl J Med 2010;363(23):2270-2
  • Zuber J, Fakhouri F, Roumenina LT, et al. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 2012;8(11):643-57
  • Qu H, Ricklin D, Bai H, et al. New analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties. Immunobiology 2013;218(4):496-505
  • 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 2012;119(26):6307-16
  • Schmidt CQ, Bai H, Lin Z, et al. Rational engineering of a minimized immune inhibitor with unique triple-targeting properties. J Immunol 2013;190(11):5712-21
  • Risitano AM, Ricklin D, Huang Y, et al. Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria. Blood 2014;123(13):2094-101
  • Kourtzelis I, Markiewski MM, Doumas M, et al. Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis. Blood 2010;116(4):631-9
  • Silasi-Mansat R, Zhu H, Popescu NI, et al. Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis. Blood 2010;116(6):1002-10
  • Nicholson-Weller A, March JP, Rosenfeld SI, Austen KF. Affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria are deficient in the complement regulatory protein, decay accelerating factor. Proc Natl Acad Sci USA 1983;80(16):5066-70
  • Holguin MH, Fredrick LR, Bernshaw NJ, et al. 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 1989;84(1):7-17
  • Kinoshita T, Medof ME, Silber R, Nussenzweig V. Distribution of decay-accelerating factor in the peripheral blood of normal individuals and patients with paroxysmal nocturnal hemoglobinuria. J Exp Med 1985;162(1):75-92
  • Meri S, Morgan BP, Davies A, et al. Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunology 1990;71(1):1-9
  • Pangburn MK, Muller-Eberhard HJ. Initiation of the alternative complement pathway due to spontaneous hydrolysis of the thioester of C3. Ann N Y Acad Sci 1983;421:291-8
  • Pangburn MK, Schreiber RD, Muller-Eberhard HJ. Deficiency of an erythrocyte membrane protein with complement regulatory activity in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci USA 1983;80(17):5430-4
  • Hamad OA, Nilsson PH, Wouters D, et al. Complement component C3 binds to activated normal platelets without preceding proteolytic activation and promotes binding to complement receptor 1. J Immunol 2010;184(5):2686-92
  • Hamad OA, Ekdahl KN, Nilsson PH, et al. Complement activation triggered by chondroitin sulfate released by thrombin receptor-activated platelets. J Thromb Haemost 2008;6(8):1413-21
  • Markiewski MM, Nilsson B, Ekdahl KN, et al. Complement and coagulation: strangers or partners in crime? Trends Immunol 2007;28(4):184-92
  • Hamad OA, Back J, Nilsson PH, et al. Platelets, complement, and contact activation: partners in inflammation and thrombosis. Adv Exp Med Biol 2012;946:185-205
  • Amara U, Flierl MA, Rittirsch D, et al. Molecular intercommunication between the complement and coagulation systems. J Immunol 2010;185(9):5628-36
  • 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 2006;177(7):4794-802
  • Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol 2013;190(8):3831-8
  • Rother RP, Rollins SA, Mojcik CF, , and et al. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 2007;25(11):1256-64
  • Parker C. Eculizumab for paroxysmal nocturnal haemoglobinuria. Lancet 2009;373(9665):759-67
  • Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol 2010;11(9):785-97
  • Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol 2013;190(8):3839-47
  • Ricklin D, Lambris JD. Progress and trends in complement therapeutics. Adv Exp Med Biol 2013;735:1-22
  • Reis S, Falcao DA, Isaac L. Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H. Scand J Immunol 2006;63(3):155-68
  • Ricklin D, Lambris JD. Complement-targeted therapeutics. Nat. Biotechnol 2007;25(11):1265-75
  • Matis LA, Rollins SA. Complement-specific antibodies: designing novel anti-inflammatories. Nat Med 1995;1(8):839-42
  • Song H, He C, Knaak C, et al. Complement receptor 2-mediated targeting of complement inhibitors to sites of complement activation. J Clin Invest 2003;111(12):1875-85
  • Nunn MA, Sharma A, Paesen GC, et al. Complement inhibitor of C5 activation from the soft tick Ornithodoros moubata. J Immunol 2005;174(4):2084-91
  • Roversi P, Lissina O, Johnson S, et al. The structure of OMCI, a novel lipocalin inhibitor of the complement system. J Mol Biol 2007;369(3):784-93
  • Barratt-Due A, Thorgersen EB, Lindstad JK, et al. Ornithodoros moubata complement inhibitor is an equally effective C5 inhibitor in pigs and humans. J Immunol 2011;187(9):4913-19
  • Weston-Davies WH, Westwood JP, Nunn M, et al. Phase I Clinical Trial of Coversin, a Novel Complement C5 and LTB4 Inhibitor. Presented at 7th International Conference on Complement Therapeutics, Aegean Conferences; Aldemar Olympian Village, Olympia, Greece; 2014
  • Feldwisch J, Tolmachev V. Engineering of affibody molecules for therapy and diagnostics. Methods Mol Biol 2012;899:103-26
  • Strömberg P. Introducing SOBI002, a small Affibody-ABD fusion protein targeting complement component C5. Presented at 7th International Conference of Complement Therapeutics, Aegean Conferences; Aldemar Olympian Village, Olympia, Greece; 2014
  • Shaughnessy AF. Monoclonal antibodies: magic bullets with a hefty price tag. BMJ 2012;12:345
  • Vlieghe P, Lisowski V, Martinez J, Khrestchatisky M. Synthetic therapeutic peptides: science and market. Drug Discov Today 2010;15(1-2):40-56
  • Lindorfer MA, Pawluczkowycz AW, Peek EM, et al. A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement. Blood 2010;115(11):2283-91
  • Paixao-Cavalcante D, Torreira E, Lindorfer MA, et al. A humanized antibody that regulates the alternative pathway convertase: potential for therapy of renal disease associated with nephritic factors. J Immunol 2014;192(10):4844-51
  • Whaley K, Ruddy S. Modulation of the alternative complement pathways by beta 1 H globulin. J Exp. Med 1976;144(5):1147-63
  • Ferreira VP, Pangburn MK. Factor H mediated cell surface protection from complement is critical for the survival of PNH erythrocytes. Blood 2007;110(6):2190-2
  • Safety and Pharmacokinetics of TT30 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH). Available from: http://clinicaltrials.gov/ct2/show/NCT01335165
  • Maekawa T, Abe T, Hajishengallis E, et al. Genetic and intervention studies implicating complement c3 as a major target for the treatment of periodontitis. J Immunol 2014;192(12):6020-7
  • Jevsevar S, Kunstelj M, Porekar VG. PEGylation of therapeutic proteins. Biotechnol J 2010;5(1):113-28
  • McDonnell T, Ioannou Y, Rahman A. PEGylated drugs in rheumatology--why develop them and do they work? Rheumatology (Oxford) 2014;53(3):391-6
  • Kaudlay P, Hua H, He G, et al. Red cell complement loading in PNH patients on eculizumab is associated with a C3 polymorphism which influences C3 function, predicts for increased extravascular hemolysis and provides a rationale for C3 inhibition. Presented at Annual Meeting of the American Society of Hematology; New Orleans, LA, USA; 2013
  • Helley D, de Latour RP, Porcher R, et al. Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Haematologica 2010;95(4):574-81
  • 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 2012;130(3):361-8
  • Lupu F, Keshari RS, Lambris JD, et al. Crosstalk between the coagulation and complement systems in sepsis. Thromb Res 2014;133(Suppl 1):S28-31
  • Keshari RS, Silasi-Mansat R, Zhu H, et al. Acute Lung Injury and Fibrosis in a Baboon Model of Escherichia coli Sepsis. Am J Respir Cell Mol Biol 2014;50(2):439-50

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.