The polygenic nature of inhibitors in hemophilia A: Results from the,HemophiliaInhibitor Genetics Study (HIGS) Combined Cohort

Blood

Volumn 121, Issue 8, 2013, Pages 1446-1454

  Astermark, Jan ^a   Donfield, Sharyne M ^b   Gomperts, Edward D ^c   Schwarz, John ^b   Menius, Erika D ^b   Pavlova, Anna ^d   Oldenburg, Johannes ^d   Kessing, Bailey ^e   DiMichele, Donna M ^f,h   Shapiro, Amy D ^g   Winkler, Cheryl A ^a   Berntorp, Erik ^a  

^a LUND UNIVERSITY   (Sweden)

^b RHO INC   (United States)

^c CHILDREN S HOSPITAL LOS ANGELES   (United States)

^d UNIVERSITY HOSPITAL BONN   (Germany)

^e SAIC FREDERICK INC   (United States)

^f WEILL CORNELL MEDICAL COLLEGE   (United States)

^g INDIANA HEMOPHILIA AND THROMBOSIS CENTER   (United States)

^h NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

Author keywords

Potentially decisive markers have been identified, indicating the importance of further evaluation of intracellular signaling pathways; The data demonstrate the complexity of the genetic contribution to inhibitor development in people with hemophilia a

Indexed keywords

ALOX5AP PROTEIN; CSF1R PROTEIN; DOCK2 PROTEIN; F13A1 PROTEIN; HERMES ANTIGEN; HSP90B1 PROTEIN; IGSF2 PROTEIN; IQGAP2 PROTEIN; MAP2K4 PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 9; MSR1 PROTEIN; PCGF2 PROTEIN; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN; PTPRE PROTEIN; PTPRM PROTEIN; PTPRN2 PROTEIN; TNFRSF21 PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CHROMOSOME INVERSION; FAMILY HISTORY; GENE DELETION; GENE INSERTION; GENOTYPE; HEMOPHILIA A; HEREDITY; HUMAN; IMMUNE RESPONSE; MAJOR CLINICAL STUDY; MISSENSE MUTATION; NONSENSE MUTATION; PREDICTION; PRIORITY JOURNAL; SIBLING; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84874393543     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2012-06-434803     Document Type: Article

References (50)

1. Astermark J. Inhibitor development: patient determined risk factors. Haemophilia. 2010;16(102): 66-70.
2. Oldenburg J, El-Maarri O, Schwaab R. Inhibitor development in correlation to factor VIII genotypes. Haemophilia. 2002;8(2):23-29. (Pubitemid 34506224)
3. Astermark J, Oldenburg J, Escobar M, White 2nd G, Berntorp E. The malmo international brother study (MIBS). Genetic defects and inhibitor development in siblings with severe hemophilia A. Haematologica. 2005;90(7):924.
4. 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(12):2006-2015.
5. Astermark J, Berntorp E, White G, Kroner B, MIBS Study Group. The Malmo International Brother Study (MIBS): further support for genetic predisposition to inhibitor development. Haemophilia. 2001;7(3):267-272. (Pubitemid 32471960)
6. Chaves D, Belisario A, Castro G, Santoro M, Rodrigues C. Analysis of cytokine genes polymorphism as markers for inhibitor development in haemophilia A. Int J Immunogenet. 2010;37(2): 79-82.
7. Gaitonde P, Peng A, Straubinger RM, Bankert RB, Balu-Iyer SV. Downregulation of CD40 signal and induction of TGF-beta by phosphatidylinositol mediatesreduction in immunogenicity against recombinant human factor VIII. J Pharm Sci. 2012;101(1): 48-55.
8. 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(4):641-649.
9. Lu Y, Ding Q, Dai J, Wang H, Wang X. Impact of polymorphisms in genes involved in autoimmune disease on inhibitor development in Chinese patients with haemophilia A. Thromb Haemost. 2012;107(1):30-36.
10. Astermark J, Oldenburg J, Carlson J, et al. Polymorphisms in the TNFA gene and the risk of inhibitor development in patients with hemophilia A. Blood. 2006;108(12):3739-3745. (Pubitemid 44864553)
11. Astermark J, Oldenburg J, Pavlova A, Berntorp E, Lefvert AK, MIBS Study Group. Polymorphisms in the IL10 but not in the IL1beta and IL4 genes are associated with inhibitor development in patients with hemophilia A. Blood. 2006;107(8):3167.
12. Astermark J, Wang X, Oldenburg J, Berntorp E, Lefvert AK, MIBS Study Group. Polymorphisms in the CTLA 4 gene and inhibitor development in patients with severe hemophilia A. J Thromb Haemost. 2007;5(2):263-265. (Pubitemid 46139449)
13. 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(5):747- 766.
14. Hilgartner MW, Donfield SM, Willoughby A, et al. Hemophilia Growth and Development Study: Design, Methods Entry Data. Am J Pediatr Hematol Oncol. 1993;15(2):208-218. (Pubitemid 23143090)
15. Verbruggen B, Novakova I,Wessels H, Boezeman J, van den Berg M, Mauser-Bunschoten E. The nijmegen modification of the bethesda assay for factor VIII:C inhibitors: improved specificity and reliability. Thromb Haemost. 1995;73(2):247-251.
16. Oldenburg J. Mutation profiling in haemophilia A. Thromb Haemost. 2001;85(4):577-579. (Pubitemid 32293689)
17. Lakich D, Kazazian HH, Antonarakis SE, Gitschier J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat Genet. 1993;5(3):236-241. (Pubitemid 23330385)
18. Price AL, Patterson NJ, Plenge RM,Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38:904-909. (Pubitemid 44141658)
19. de Bakker PIW, Ferreira MAR, Jia X, Neale BM, Raychaudhuri S, Voight BF. Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum Mol Genet. 2008; 17(R2):R122-R128.
20. SAS Institute Inc. SAS 9.1. 3 Help and Documentation. Cary, NC: SAS Institute Inc; 2004.
21. Gao X, Starmer J, Martin ER. (2008) A multiple testing correction method for genetic association studies using correlated single nucleotide polymorphisms. Genet Epidemiol. 2008;32:361-369. (Pubitemid 351656307)
22. Kurnik K, Bidlingmaier C, Engl W, Chehadeh H,Reipert B, Auerswald G. New early prophylaxis regimen that avoids immunological danger signals can reduce FVIII inhibitor development. Haemophilia. 2010;16(2):256-262.
23. Jaeschke A, Rinco'n M, Doran B, et al. Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes. Proc Natl Acad Sci U S A. 2005; 102(19):6931.
24. Kant S, Swat W, Zhang S, et al. TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway. Genes Dev. 2011; 25(19):2069-2078.
25. Andrae J, Gallini R, Betsholtz C. Role of plateletderived growth factors in physiology and medicine. Genes Dev. 2008;22(10):1276.
26. Sparmann A, Van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer. 2006;6(11):846-856. (Pubitemid 44629896)
27. Kimura M, Koseki Y, Yamashita M, et al. Regulation of Th2 Cell Differentiation by mel-18, a Mammalian Polycomb Group Gene. Immunity. 2001; 15(2):275-287. (Pubitemid 32816876)
28. Reif K, Cyster JG. The CDM protein DOCK2 in lymphocyte migration. Trends Cell Biol. 2002; 12(8):368-373. (Pubitemid 35015146)
29. Cimino PJ, Sokal I, Leverenz J, Fukui Y, Montine TJ. DOCK2 is a microglial specific regulator of central nervous system innate immunity found in normal and Alzheimer's disease brain. Am J Pathol. 2009; 175(4):1622-1630.
30. Gotoh K, Tanaka Y, Nishikimi A, et al. Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation. J Exp Med. 2010;207(4): 721-730.
31. Johnson P, Ruffell B. CD44 and its role in inflammation and inflammatory diseases. Inflamm Allergy Drug Targets. 2009;8(3):208.
32. Yasuda M, Nakano K, Yasumoto K, Tanaka Y. CD44: functional relevance to inflammation and malignancy. Histol Histopathol. 2002;17(3):945- 950.
33. Pathmanathan S, Hamilton E, Atcheson E, Timson DJ. The interaction of IQGAPs with calmodulin-like proteins. Biochem Soc Trans. 2011;39(2):694.
34. White CD, Khurana H, Gnatenko DV, et al. IQGAP1 and IQGAP2 are reciprocally altered in hepatocellular carcinoma. BMC Gastroenterol. 2010;10:125.
35. Hume DA, MacDonald KPA. Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood. 2012;119(8):1810- 1820.
36. Warger T, Hilf N, Rechtsteiner G, et al. Interaction of TLR2 and TLR4 ligands with the N-terminal domain of Gp96 amplifies innate and adaptive immune responses. J Biol Chem. 2006;281(32): 22545-22553.
37. Han JM, Kwon NH, Lee JY, et al. Identification of gp96 as a novel target for treatment of autoimmune disease in mice. PLoS One. 2010;5(3): e9792.
38. Koma'romi I, Bagoly Z, Muszbek L. Factor XIII: novel structural and functional aspects. J Thromb Haemost. 2011;9(1):9-20.
39. Sjoberg K, Eriksson S, Tenngart B, Roth EB, Leffler H, Stenberg P. Factor XIII and tissue transglutaminase antibodies in coeliac and inflammatory bowel disease. Autoimmunity. 2002;35(5): 357-364. (Pubitemid 35189678)
40. Bouloc A, Bagot M, Delaire S, Bensussan A, Boumsell L. Triggering CD101 molecule on human cutaneous dendritic cells inhibits T cell proliferation via IL-10 production. Eur J Immunol. 2000;30(11):3132-3139.
41. Fernandez I, Zeiser R, Karsunky H, et al. CD101surface expression discriminates potency among murine FoxP3- regulatory T cells. J Immunol. 2007;179(5):2808-2814.
42. Evans JF, Ferguson AD, Mosley RT, Hutchinson JH. What's all the FLAP about?: 5-lipoxygenaseactivating protein inhibitors for inflammatory diseases. Trends Pharmacol Sci. 2008;29(2):72-78.
43. Dong C, Davis RJ, Flavell RA. Signaling by the JNK group of MAP kinases. J Clin Immunol. 2001;21(4):253-257. (Pubitemid 32652596)
44. Hammaker DR, Boyle DL, Chabaud-Riou M, Firestein GS. Regulation of c-Jun N-terminal kinase by MEKK-2 and mitogen-activated protein kinase kinase kinases in rheumatoid arthritis. J Immunol. 2004;172(3):1612-1618. (Pubitemid 38116808)
45. Forrest ARR, Taylor DF, Crowe ML, et al. Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases. Genome Biol. 2006;7(1):R5.
46. Mustelin T, Taske'n K. Positive and negative regulation of T-cell activation through kinases and phosphatases. Biochem J. 2003;371(Pt 1):15.
47. Bowdish DME, Gordon S. Conserved domains of the class A scavenger receptors: evolution and function. Immunol Rev. 2009;227(1):19-31.
48. Nelson WG, De Marzo AM, De Weese TL, Isaacs WB. The role of inflammation in the pathogenesis of prostate cancer. J Urol. 2004;172(5 Pt 2):S6-11;discussion S11-12.
49. Matesanz-Isabel J, Sintes J, Llinas L, de Salort J, La'zaro A, Engel P. New B-cell CD molecules. Immunol lett. 2011;134(2):104-112.
50. Benschop R, Wei T, Na S. Tumor necrosis factor receptor superfamily member 21: TNFR-related death receptor-6, DR6. Adv Exp Med Biol. 2009; 647:186-194.