Inhibitory antibodies in hemophilia A

Current Opinion in Hematology

Volumn 19, Issue 5, 2012, Pages 399-405

  Pratt, Kathleen P ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

antidrug antibodies; hemophilia A; inhibitors; therapeutic proteins

Indexed keywords

BLOOD CLOTTING FACTOR 8; BLOOD CLOTTING FACTOR 8 ANTIBODY; NEUTRALIZING ANTIBODY;

ANTIBODY PRODUCTION; ANTIGEN PRESENTING CELL; B LYMPHOCYTE; DENDRITIC CELL; GENETIC RISK; HEMOPHILIA A; HUMAN; IMMUNOGENICITY; IMMUNOLOGICAL TOLERANCE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW;

ANIMALS; B-LYMPHOCYTES; BLOOD COAGULATION FACTOR INHIBITORS; FACTOR VIII; HEMOPHILIA A; HUMANS; IMMUNE TOLERANCE; RISK FACTORS; T-LYMPHOCYTES;

EID: 84865418932     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/MOH.0b013e328356ed37     Document Type: Review

References (92)

1. Aledort LM, Dimichele DM. Inhibitors occur more frequently in African-American and Latino haemophiliacs. Haemophilia 1998; 4:68.
2. Miller CH, Benson J, Ellingsen D, et al. F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity. Haemophilia 2012; 18:375-382.
3. Carpenter SL, Michael Soucie J, Sterner S, Presley R. Increased prevalence of inhibitors in Hispanic patients with severe haemophilia A enrolled in the Universal Data Collection database. Haemophilia 2012; 18:e260-e265.
4. Wang XF, Zhao YQ, Yang RC, et al. The prevalence of factor VIII inhibitors and genetic aspects of inhibitor development in Chinese patients with haemophilia A. Haemophilia 2010; 16:632-639.
5. Gouw SC, van den Berg HM, Oldenburg J, et al. F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis. Blood 2012; 119:2922-2934.
6. Hausl C, Ahmad RU, Schwarz HP, et al. Preventing restimulation of memory B cells in hemophilia A: a potential new strategy for the treatment of antibodydependent immune disorders. Blood 2004; 104:115-122. (Pubitemid 38879846)
7. van Helden PM, Kaijen PH, Fijnvandraat K, et al. Factor VIII-specific memory B cells in patients with hemophilia A. J Thromb Haemost 2007; 5:2306-2308. (Pubitemid 47617887)
8. Hausl C, Ahmad RU, Sasgary M, et al. High-dose factor VIII inhibits factor VIII-specific memory B cells in hemophilia A with factor VIII inhibitors. Blood 2005; 106:3415-3422. (Pubitemid 41609176)
9. van Helden PM, Van Haren SD, Fijnvandraat K, et al. Factor VIII-specific B cell responses in haemophilia A patients with inhibitors. Haemophilia 2010; 16:35-43.
10. Reipert BM, Allacher P, Hausl C, et al. Modulation of factor VIII-specific memory B cells. Haemophilia 2010; 16:25-34.
11. Pordes AG, Baumgartner CK, Allacher P, et al. T cell-independent restimulation of FVIII-specific murine memory B cells is facilitated by dendritic cells together with toll-like receptor 7 agonist. Blood 2011; 118:3154-3162.
12. Allacher P, Baumgartner CK, Pordes AG, et al. Stimulation and inhibition of FVIII-specific memory B-cell responses by CpG-B (ODN 1826), a ligand for Toll-like receptor 9. Blood 2011; 117:259-267.
13. Navarrete AM, Dasgupta S, Teyssandier M, et al. Endocytic receptor for procoagulant factor VIII: relevance to inhibitor formation. Thromb Haemost 2010; 104:1093-1098.
14. Herczenik E, van Haren SD, Wroblewska A, et al. Uptake of blood coagulation factor VIII by dendritic cells is mediated via its C1 domain. J Allergy Clin Immunol 2012; 129:501-509; 9 e1-e5. This study identifies a specific loop in the FVIII protein that is involved in FVIII update by APCs.
15. Repesse Y, Dasgupta S, Navarrete AM, et al. Mannose-sensitive receptors mediate the uptake of factor VIII therapeutics by human dendritic cells. J Allergy Clin Immunol 2012; 129:1172-1173.
16. Delignat S, Repesse Y, Navarrete AM, et al. Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A. Haemophilia 2012; 18:248-254.
17. van Haren SD, Herczenik E, ten Brinke A, et al. HLA-DR-presented peptide repertoires derived from human monocyte-derived dendritic cells pulsed with blood coagulation factor VIII. Mol Cell Proteom 2011; 10:M110 002246.
18. van Haren SD, Wroblewska A, Fischer K, et al. Requirements for immune recognition and processing of factor VIII by antigen-presenting cells. Blood Rev 2012; 26:43-49.
19. Astermark J, Altisent C, Batorova A, et al. Nongenetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report. Haemophilia 2010; 16:747-766.
20. Lozier JN, Rosenberg PS, Goedert JJ, Menashe I. A case-control study reveals immunoregulatory gene haplotypes that influence inhibitor risk in severe haemophilia A. Haemophilia 2011; 17:641-649.
21. Hay CR, Ollier W, Pepper L, et al. HLA class II profile: a weak determinant of factor VIII inhibitor development in severe haemophilia A. UKHCDO Inhibitor Working Party. Thromb Haemost 1997; 77:234-237. (Pubitemid 27084906)
22. Pavlova A, Delev D, Lacroix-Desmazes S, et al. Impact of polymorphisms of the major histocompatibility complex class II, interleukin-10, tumor necrosis factor-alpha and cytotoxic T-lymphocyte antigen-4 genes on inhibitor development in severe hemophilia A. J Thromb Haemost 2009; 7:2006-2015.
23. White GC 2nd, Kempton CL, Grimsley A, et al. Cellular immune responses in hemophilia: why do inhibitors develop in some, but not all hemophiliacs? J Thromb Haemost 2005; 3:1676-1681. (Pubitemid 41716553)
24. De Barros MF, Herrero JC, Sell AM, et al. Influence of class I and II HLA alleles on inhibitor development in severe haemophilia A patients from the South of Brazil. Haemophilia 2012; 18:e236-e240.
25. Howard TE, Yanover C, Mahlangu J, et al. Haemophilia management: time to get personal? Haemophilia 2011; 17:721-728.
26. Barbosa MD. Immunogenicity of biotherapeutics in the context of developing biosimilars and biobetters. Drug Discov Today 2011; 16:345-353.
27. Sauerborn M, Brinks V, Jiskoot W, Schellekens H. Immunological mechanism underlying the immune response to recombinant human protein therapeutics. Trends Pharmacol Sci 2010; 31:53-59.
28. Scott DW, De Groot AS. Can we prevent immunogenicity of human protein drugs? Ann Rheum Dis 2010; 69 (Suppl 1):i72-i76.
29. Jacquemin M, Vantomme V, Buhot C, et al. CD4 + T-cell clones specific for wild-type factor VIII: a molecular mechanism responsible for a higher incidence of inhibitor formation in mild/moderate hemophilia A. Blood 2003; 101:1351-1358. (Pubitemid 36182506)
30. James EA, Kwok WW, Ettinger RA, et al. T-cell responses over time in a mild hemophilia A inhibitor subject: epitope identification and transient immunogenicity of the corresponding self-peptide. J Thromb Haemost 2007; 5:2399-2407. (Pubitemid 350154349)
31. Ettinger RA, James EA, Kwok WW, et al. Lineages of human T-cell clones, including T helper 17/T helper 1 cells, isolated at different stages of antifactor VIII immune responses. Blood 2009; 114:1423-1428.
32. Ettinger RA, James EA, Kwok WW, et al. HLA-DR-restricted T-cell responses to factor VIII epitopes in a mild haemophilia A family with missense substitution A2201P. Haemophilia 2010; 16:44-55.
33. James EA, van Haren SD, Ettinger RA, et al. T-cell responses in two unrelated hemophilia A inhibitor subjects include an epitope at the factor VIII R593C missense site. J Thromb Haemost 2011; 9:689-699.
34. Levinson B, Kenwrick S, Gamel P, et al. Evidence for a third transcript from the human factor VIII gene. Genomics 1992; 14:585-589.
35. Shovlin CL, Angus G, Manning RA, et al. Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension. PLoS One 2010; 5: e9154.
36. Frischmeyer PA, Dietz HC. Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet 1999; 8:1893-1900. (Pubitemid 29458667)
37. Irimia M, Blencowe BJ. Alternative splicing: decoding an expansive regulatory layer. Curr Opin Cell Biol 2012; 24:323-332.
38. Hollestelle MJ, Thinnes T, Crain K, et al. Tissue distribution of factor VIII gene expression in vivo: a closer look. Thromb Haemost 2001; 86:855-861. (Pubitemid 32834197)
39. Jacquemin M, Neyrinck A, Hermanns MI, et al. FVIII production by human lung microvascular endothelial cells. Blood 2006; 108:515-517. (Pubitemid 44061350)
40. Shahani T, Lavend'homme R, Luttun A, et al. Activation of human endothelial cells from specific vascular beds induces the release of a FVIII storage pool. Blood 2010; 115:4902-4909.
41. Banerjee DK, Tavarez JJ, Oliveira CM. Expression of blood clotting factor VIII:C gene in capillary endothelial cells. FEBS Lett 1992; 306:33-37.
42. Do H, Healey JF, Waller EK, Lollar P. Expression of factor VIII by murine liver sinusoidal endothelial cells. J Biol Chem 1999; 274:19587-19592.
43. Howard TE. Factor VIII gene haplotype and inhibitor development [abstract]. Thromb Haemost 2011; 9:1. Abstr. SY-MO-001.
44. Hay CR. The epidemiology of factor VIII inhibitors. Haemophilia 2006; 12 (Suppl 6):23-28.
45. Gouw SC, van den Berg HM. The multifactorial etiology of inhibitor development in hemophilia: genetics and environment. Semin Thromb Hemost 2009; 35:723-734.
46. Kaveri S, Mannucci PM, Kurth MH, et al. von Willebrand factor: what is its role in the immune response in haemophilia? Haemophilia 2011; 17:e235-e238.
47. Gringeri A, Ofosu FA, Grancha S, et al. Understanding FVIII/VWF complex: report from a symposium of XXIX WFH meeting 2010. Haemophilia 2012; 18:469-475.
48. Aledort LM, Navickis RJ, Wilkes MM. Best evidence on B-domain deletion and the immunogenicity of recombinant factor VIII. J Thromb Haemost 2011; 9:2325-2327.
49. Aledort LM, Navickis RJ, Wilkes MM. Can B-domain deletion alter the immunogenicity of recombinant factor VIII? A meta-analysis of prospective clinical studies. J Thromb Haemost 2011; 9:2180-2192.
50. Mancuso ME, Mannucci PM, Rocino A, et al. Source and purity of factor VIII products as risk factors for inhibitor development in patients with hemophilia A. J Thromb Haemost 2012; 10:781-789.
51. Mannucci PM, Gringeri A, Peyvandi F, Santagostino E. Factor VIII products and inhibitor development: the SIPPET study (survey of inhibitors in plasma-product exposed toddlers). Haemophilia 2007; 13 (Suppl 5): 65-68. (Pubitemid 350253407)
52. Dasgupta S, Navarrete AM, Bayry J, et al. A role for exposed mannosylations in presentation of human therapeutic self-proteins to CD4 + T lymphocytes. Proc Natl Acad Sci USA 2007; 104:8965-8970. (Pubitemid 47175420)
53. Reipert B, Arruda V, Lillicrap D. Animal models of inhibitors. Haemophilia 2010; 16 (Suppl 5):47-53.
54. Waters B, Qadura M, Burnett E, et al. Anti-CD3 prevents factor VIII inhibitor development in hemophilia A mice by a regulatory CD4 +CD25 +-dependent mechanism and by shifting cytokine production to favor a Th1 response. Blood 2009; 113:193-203.
55. Liu CL, Ye P, Yen BC, Miao CH. In vivo expansion of regulatory T cells with IL-2/IL-2 mAb complexes prevents antifactor VIII immune responses in hemophilia A mice treated with factor VIII plasmid-mediated gene therapy. Mol Ther 2011; 19:1511-1520.
56. Miao CH. Tilt balance towards regulation: evolving new strategy for treatment of hemophilia inhibitors. J Thromb Haemost 2011; 9:1521-1523.
57. Sabatino DE, Nichols TC,Merricks E, et al. Animal models of hemophilia. Prog Mol Biol Transl Sci 2012; 105:151-209.
58. Sule GJ, Suzuki M, Guse K, et al. Cytokine-conditioned dendritic cells induce humoral tolerance to protein therapy in mice. Hum Gene Ther 2012. [Epub ahead of print]
59. Scott DW, Lozier JN. Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation. Br J Haematol 2012; 156:295-302.
60. Su RJ, Epp A, Latchman Y, et al. Suppression of FVIII inhibitor formation in hemophilic mice by delivery of transgene modified apoptotic fibroblasts. Mol Ther 2010; 18:214-222.
61. Su RJ, Epp A, Feng J, et al. Suppression of the immune response to FVIII in hemophilia A mice by transgene modified tolerogenic dendritic cells. Mol Ther 2011; 19:1896-1904.
62. van Helden PM, Unterthurner S, Hermann C, et al. Maintenance and break of immune tolerance against human factor VIII in a new transgenic hemophilic mouse model. Blood 2011; 118:3698-3707.
63. Jones TD, Phillips WJ, Smith BJ, et al. Identification and removal of a promiscuous CD4 + T cell epitope from the C1 domain of factor VIII. J Thromb Haemost 2005; 3:991-1000. (Pubitemid 41632831)
64. Pratt KP, Thompson AR. B-cell and T-cell epitopes in antifactor VIII immune responses. Clin Rev Allergy Immunol 2009; 37:80-95.
65. Weber CA, Mehta PJ, Ardito M, et al. T cell epitope: friend or foe? Immunogenicity of biologics in context. Adv Drug Deliv Rev 2009; 61: 965-976.
66. Moise L, Song C, Martin WD, et al. Effect of HLA DR epitope de-immunization of Factor VIII in vitro and in vivo. Clin Immunol 2012; 142:320-331.
67. De Groot AS, Moise L, McMurry JA, et al. Activation of natural regulatory T cells by IgG Fc-derived peptide 'Tregitopes'. Blood 2008; 112:3303-3311.
68. Elyaman W, Khoury SJ, Scott DW, De Groot AS. Potential application of tregitopes as immunomodulating agents in multiple sclerosis. Neurol Res Int 2011; 2011:256460.
69. Miao CH. Immunomodulation for inhibitors in hemophilia A: the important role of Treg cells. Expert Rev Hematol 2010; 3:469-483.
70. Moghimi B, Sack BK, Nayak S, et al. Induction of tolerance to factor VIII by transient co-administration with rapamycin. J Thromb Haemost 2011; 9:1524-1533.
71. Healey JF, Lubin IM, Nakai H, et al. Residues 484-508 contain a major determinant of the inhibitory epitope in the A2 domain of human factor VIII. J Biol Chem 1995; 270:14505-14509.
72. Lollar P, Parker ET, Curtis JE, et al. Inhibition of human factor VIIIa by anti-A2 subunit antibodies. J Clin Invest 1994; 93:2497-2504.
73. Lubin IM, Healey JF, Scandella D, et al. Elimination of a major inhibitor epitope in factor VIII. J Biol Chem 1994; 269:8639-8641. (Pubitemid 24209165)
74. Meeks SL, Healey JF, Parker ET, et al. Antihuman factor VIII C2 domain antibodies in hemophilia A mice recognize a functionally complex continuous spectrum of epitopes dominated by inhibitors of factor VIII activation. Blood 2007; 110:4234-4242. (Pubitemid 351377787)
75. Meeks SL, Healey JF, Parker ET, et al. Nonclassical anti-C2 domain antibodies are present in patients with factor VIII inhibitors. Blood 2008; 112:1151-1153.
76. Nguyen P-C LK, Schuman JT, Meeks SL, et al. High-resolution mapping of B-cell epitopes on the factor VIII C2 domain using surface plasmon resonance. Blood 2011; 118:203.
77. Egler AT, Jakuschev S, Schuldenzucker U, et al. The B-cell epitope of the monoclona anti-factor VIII antibody ESH8 characterized bt peptide array analysis. Thromb Haemost 2008; 99:634-637. (Pubitemid 351549304)
78. Lollar P. Mapping factor VIII inhibitor epitopes using hybrid human/porcine factor VIII molecules. Haematologica 2000; 85 (10 Suppl):26-28.
79. Barrow RT, Healey JF, Jacquemin MG, et al. Antigenicity of putative phospholipid membrane-binding residues in factor VIII. Blood 2001; 97:169-174. (Pubitemid 32061257)
80. Parker ET, Healey JF, Barrow RT, et al. Reduction of the inhibitory antibody response to human factor VIII in hemophilia A mice by mutagenesis of the A2 domain B-cell epitope. Blood 2004; 104:704-710. (Pubitemid 38970563)
81. Lollar P. Pathogenic antibodies to coagulation factors. Part one: factor VIII and factor IX. J Thromb Haemost 2004; 2:1082-1095. (Pubitemid 40186081)
82. Ansong C, Miles SM, Fay PJ. Epitope mapping factor VIII A2 domain by affinity-directed mass spectrometry: residues 497-510 and 584-593 comprise a discontinuous epitope for the monoclonal antibody R8B12. J Thromb Haemost 2006; 4:842-847.
83. Griffiths AE, Wang W, Hagen FK, Fay PJ. Use of affinity-directed liquid chromatography-mass spectrometry to map the epitopes of a factor VIII inhibitor antibody fraction. J Thromb Haemost 2011; 9:1534-1540.
84. Albert T, Egler C, Jakuschev S, et al. The B-cell epitope of the monoclonal antifactor VIII antibody ESH8 characterized by peptide array analysis. Thromb Haemost 2008; 99:634-637. (Pubitemid 351549304)
85. Spiegel PC Jr, Jacquemin M, Saint-Remy JM, et al. Structure of a factor VIII C2 domain-immunoglobulin G4kappa Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII. Blood 2001; 98:13-19.
86. von Depka M. Managing acute bleeds in the patient with haemophilia and inhibitors: options, efficacy and safety.Haemophilia 2005; 11(Suppl 1):18-23.
87. Barrow RT, Lollar P. Neutralization of antifactor VIII inhibitors by recombinant porcine factor VIII. J Thromb Haemost 2006; 4:2223-2229. (Pubitemid 44400302)
88. Toschi V. OBI-1, porcine recombinant Factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies against human Factor VIII. Curr Opin Mol Ther 2010; 12:617-625.
89. Pautard B, D'Oiron R, Li Thiao Te V, et al. Successful immune tolerance induction by FVIII in hemophilia A patients with inhibitor may occur without deletion of FVIII-specific T cells. J Thromb Haemost 2011; 9:1163-1170.
90. Waters B, Lillicrap D. The molecular mechanisms of immunomodulation and tolerance induction to factor VIII. J Thromb Haemost 2009; 7:1446-1456.
91. Hay CR, DiMichele DM. The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood 2012; 119:1335-1344.
92. Di Michele DM. Immune tolerance induction in haemophilia: evidence and the way forward. J Thromb Haemost 2011; 9 (Suppl 1):216-225.