Pharmacogenetics of inflammatory bowel disease

Best Practice and Research: Clinical Gastroenterology

Volumn 18, Issue 3, 2004, Pages 597-609

  Mascheretti, Silvia ^a   Croucher, Peter J P ^a   Schreiber, Stefan ^a  

^a UNIVERSITY OF KIEL   (Germany)

Author keywords

AZA 6 MP; CD; Glucocorticoids; Infliximab; NOD2; Pharmacogenetics; TPMT; UC

Indexed keywords

6 MERCAPTOPURINE DERIVATIVE; 6 METHYLTHIOINOSINE; 6 THIOURIC ACID; ADALIMUMAB; ALICAFORSEN; ATRELEUTON; AZATHIOPRINE; BUDESONIDE; CARRIER PROTEIN; CERTOLIZUMAB PEGOL; DEBRISOQUINE; DRUG METABOLIZING ENZYME; ETANERCEPT; GLUCOCORTICOID; INFLIXIMAB; MERCAPTOPURINE; MERCAPTOPURINE RIBOSIDE; MESALAZINE; METHOTREXATE; ONERCEPT; PENTOXIFYLLINE; SALAZOSULFAPYRIDINE; SEMAPIMOD; THALIDOMIDE; THIOGUANOSINE; THIOPURINE METHYLTRANSFERASE; TIOGUANINE; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; TUMOR NECROSIS FACTOR ANTIBODY; UNINDEXED DRUG;

BLOOD TOXICITY; BLOOD TRANSFUSION REACTION; BONE MARROW SUPPRESSION; CLINICAL TRIAL; DRUG ABSORPTION; DRUG ACETYLATION; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG METABOLISM; DRUG OXIDATION; DRUG PROTEIN BINDING; DRUG RESPONSE; DRUG TARGETING; DRUG TOLERABILITY; DRUG TOXICITY; ENTERITIS; GENE TARGETING; GENETIC SCREENING; GENETIC VARIABILITY; HUMAN; LEUKOPENIA; LYMPHOMA; MOUSE; MYCOSIS; NONHUMAN; OPPORTUNISTIC INFECTION; PANCREATITIS; PHARMACOGENETICS; REMISSION; REVIEW; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOCYTOPENIA; TUBERCULOSIS;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; COLITIS, ULCERATIVE; CROHN DISEASE; DRUG RESISTANCE; GLUCOCORTICOIDS; HUMANS; IMMUNOSUPPRESSIVE AGENTS;

EID: 2442649257     PISSN: 15216918     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bpg.2003.12.001     Document Type: Review

References (106)

1. Weinshilboum R. Inheritance and drug response New England Journal of Medicine 348 6 2003 529-537
2. Evans W.E. McLeod H.L. Pharmacogenomics - drug disposition, drug targets, and side effects New England Journal of Medicine 348 6 2003 538-549
3. Evans W.E. Relling M.V. Pharmacogenomics: translating functional genomics into rational therapeutics Science 286 5439 1999 487-491
4. Wilson J.F. Weale M.E. Smith A.C. et al. Population genetic structure of variable drug response Nature Genetics 29 3 2001 265-269
5. McLeod H.L. Pharmacokinetic differences between ethnic groups Lancet 359 9300 2002 78
6. Evans D.A. Mahgoub A. Sloan T.P. et al. A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population Journal of Medical Genetics 17 2 1980 102-105
7. Kalow W. The Upjohn Award Lecture 1981/La Conference Upjohn 1981. The metabolism of xenobiotics in different populations Canadian Journal of Physiology and Pharmacology 60 1 1982 1-12
8. Zhou H.H. Koshakji R.P. Silberstein D.J. et al. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites New England Journal of Medicine 320 9 1989 565-570
9. Johansson I. Lundqvist E. Bertilsson L. et al. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine Proceedings of the National Academy of Science USA 90 24 1993 11825-11829
10. Bernal M.L. Sinues B. Johansson I. et al. Ten percent of North Spanish individuals carry duplicated or triplicated CYP2D6 genes associated with ultrarapid metabolism of debrisoquine Pharmacogenetics 9 5 1999 657-660
11. Marez D. Legrand M. Sabbagh N. et al. Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution Pharmacogenetics 7 3 1997 193-202
12. Aklillu E. Persson I. Bertilsson L. et al. Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles Journal of Pharmacology and Experimental Therapeutics 278 1 1996 441-446
13. Hugot J.P. Chamaillard M. Zouali H. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease Nature 411 6837 2001 599-603
14. Ogura Y. Bonen D.K. Inohara N. et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease Nature 411 6837 2001 603-606
15. Hampe J. Cuthbert A. Croucher P.J. et al. Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations Lancet 357 9272 2001 1925-1928
16. Mascheretti S. Hampe J. Croucher P.J. et al. Response to infliximab treatment in Crohn's disease is not associated with mutations in the CARD15 (NOD2) gene: an analysis in 534 patients from two multicenter, prospective GCP-level trials Pharmacogenetics 12 7 2002 509-515
17. Vermeire S. Louis E. Rutgeerts P. et al. NOD2/CARD15 does not influence response to infliximab in Crohn's disease Gastroenterology 123 1 2002 106-611
18. Lesage S. Zouali H. Cezard J.P. et al. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease American Journal of Human Genetics 70 4 2002 845-857
19. Cuthbert A.P. Fisher S.A. Mirza M.M. et al. The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease Gastroenterology 122 4 2002 867-874
20. Abreu M.T. Taylor K.D. Lin Y.C. et al. Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease Gastroenterology 123 3 2002 679-688
21. Ahmad T. Armuzzi A. Bunce M. et al. The molecular classification of the clinical manifestations of Crohn's disease Gastroenterology 122 4 2002 854-866
22. Croucher P.J.P. Mascheretti S. Hampe J. et al. Haplotype structure and association to Crohn's disease of CARD15 mutations in two ethnically divergent populations European Journal Human Genetics 11 1 2002 6-16
23. Inoue N. Tamura K. Kinouchi Y. et al. Lack of common NOD2 variants in Japanese patients with Crohn's disease Gastroenterology 123 1 2002 86-91
24. Leong R.W. Armuzzi A. Ahmad T. et al. NOD2/CARD15 gene polymorphisms and Crohn's disease in the Chinese population Alimentary Pharmacology and Therapeutics 17 12 2003 1465-1470
25. Gough A.C. Miles J.S. Spurr N.K. et al. Identification of the primary gene defect at the cytochrome P450 CYP2D locus Nature 347 6295 1990 773-776
26. Kagimoto M. Heim M. Kagimoto K. et al. Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes Journal of Biological Chemistry 265 28 1990 17209-17214
27. Lin H.J. Han C.Y. Lin B.K. Hardy S. Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene Pharmacogenetics 4 3 1994 125-134
28. Krynetski E.Y. Schuetz J.D. Galpin A.J. et al. A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase Proceedings of the National Academy of Science USA 92 4 1995 949-953
29. Tai H.L. Krynetski E.Y. Yates C.R. et al. Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians American Journal of Human Genetics 58 4 1996 694-702
30. Drazen J.M. Yandava C.N. Dube L. et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment Nature Genetics 22 2 1999 168-170
31. Hanauer S.B. Present D.H. The state of the art in the management of inflammatory bowel disease Reviews in Gastroenterological Disorders 3 2 2003 81-92
32. Krynetski E.Y. Evans W.E. Pharmacogenetics as a molecular basis for individualized drug therapy: the thiopurine S-methyltransferase paradigm Pharmaceutical Research 16 3 1999 342-349
33. Willoughby J.M. Beckett J. Kumar P.J. Dawson A.M. Controlled trial of azathioprine in Crohn's disease Lancet 2 7731 1971 944-947
34. Lennard L. Lilleyman J.S. Van Loon J. Weinshilboum R.M. Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia Lancet 336 8709 1990 225-229
35. Hollander A.A. van Saase J.L. Kootte A.M. et al. Beneficial effects of conversion from cyclosporin to azathioprine after kidney transplantation Lancet 345 8950 1995 610-614
36. Rosenberg J.L. Wall A.J. Levin B. et al. A controlled trial of azathioprine in the management of chronic ulcerative colitis Gastroenterology 69 1 1975 96-99
37. Present D.H. Korelitz B.I. Wisch N. et al. Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study New England Journal of Medicine 302 18 1980 981-987
38. Korelitz B.I. Adler D.J. Mendelsohn R.A. Sacknoff A.L. Long-term experience with 6-mercaptopurine in the treatment of Crohn's disease American Journal of Gastroenterology 88 8 1993 1198-1205
39. George J. Present D.H. Pou R. et al. The long-term outcome of ulcerative colitis treated with 6-mercaptopurine American Journal of Gastroenterology 91 9 1996 1711-1714
40. Candy S. Wright J. Gerber M. et al. A controlled double blind study of azathioprine in the management of Crohn's disease Gut 37 5 1995 674-678
41. Present D.H. Meltzer S.J. Krumholz M.P. et al. 6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity Annals of Internal Medicine 111 8 1989 641-649
42. Connell W.R. Kamm M.A. Ritchie J.K. Lennard-Jones J.E. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience Gut 34 8 1993 1081-1085
43. Schwab M. Schaffeler E. Marx C. et al. Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism Pharmacogenetics 12 6 2002 429-436
44. Krynetski E.Y. Krynetskaia N.F. Yanishevski Y. Evans W.E. Methylation of mercaptopurine, thioguanine, and their nucleotide metabolites by heterologously expressed human thiopurine S-methyltransferase Molecular Pharmacology 47 6 1995 1141-1147
45. Tai H.L. Krynetski E.Y. Schuetz E.G. et al. Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity Proceedings of the National Academy of Science USA 94 12 1997 6444-6449
46. Colombel J.F. Ferrari N. Debuysere H. et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy Gastroenterology 118 6 2000 1025-1230
47. Dubinsky M.C. Lamothe S. Yang H.Y. et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease Gastroenterology 118 4 2000 705-713
48. Cuffari C. Hunt S. Bayless T. Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease Gut 48 5 2001 642-646
49. Szumlanski C.L. Weinshilboum R.M. Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine British Journal of Clinical Pharmacology 39 4 1995 456-459
50. Ricart E. Taylor W.R. Loftus E.V. et al. N-acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis American Journal of Gastroenterology 97 7 2002 1763-1768
51. Lichtiger S. Present D.H. Kornbluth A. et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy New England Journal of Medicine 330 26 1994 1841-1845
52. Kornbluth A. Present D.H. Lichtiger S. Hanauer S. Cyclosporin for severe ulcerative colitis: a user's guide American Journal of Gastroenterology 92 9 1997 1424-1428
53. Summers R.W. Switz D.M. Sessions J.T. Jr et al. National Cooperative Crohn's Disease Study: results of drug treatment Gastroenterology 77 4 Pt 2 1979 847-869
54. Malchow H. Ewe K. Brandes J.W. et al. European Cooperative Crohn's Disease Study (ECCDS): results of drug treatment Gastroenterology 86 2 1984 249-266
55. Lichtenstein G.R. Approach to corticosteroid-dependent and corticosteroid-refractory Crohn's disease Inflammatory Bowel Disease 7 supplement 1 2001 S23-S29
56. Plevy S.E. Corticosteroid-sparing treatments in patients with Crohn's disease American Journal of Gastroenterology 97 7 2002 1607-1617
57. Lofberg R. Rutgeerts P. Malchow H. et al. Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study Gut 39 1 1996 82-86
58. Gelbmann C.M. Prediction of treatment refractoriness in ulcerative colitis and Crohn's disease - do we have reliable markers? Inflammatory Bowel Disease 6 2 2000 123-131
59. Gelbmann C.M. Rogler G. Gross V. et al. Prior bowel resections, perianal disease, and a high initial Crohn's disease activity index are associated with corticosteroid resistance in active Crohn's disease American Journal of Gastroenterology 97 6 2002 1438-1445
60. Honda M. Orii F. Ayabe T. et al. Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis Gastroenterology 118 5 2000 859-866
61. Farrell R.J. Murphy A. Long A. et al. High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy Gastroenterology 118 2 2000 279-288
62. Ueda K. Okamura N. Hirai M. et al. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone Journal of Biological Chemistry 267 34 1992 24248-24252
63. Heresbach D. Alizadeh M. Bretagne J.F. et al. TAP gene transporter polymorphism in inflammatory bowel diseases Scandinavian Journal of Gastroenterology 32 10 1997 1022-1027
64. Gelbmann C.M. Rogler G. Gierend M. et al. Association of HLA-DR genotypes and IL-1ra gene polymorphism with treatment failure of budesonide and disease patterns in Crohn's disease European Journal of Gastroenterology and Hepatology 13 12 2001 1431-1437
65. Targan S.R. Hanauer S.B. van Deventer S.J. et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group New England Journal of Medicine 337 15 1997 1029-1035
66. Stack W.A. Mann S.D. Roy A.J. et al. Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease Lancet 349 9051 1997 521-524
67. Shetty A. Forbes A. Pharmacogenomics of response to anti-tumor necrosis factor therapy in patients with Crohn's disease American Journal of Pharmacogenomics 2 4 2002 215-221
68. Sandborn W.J. Strategies for targeting tumour necrosis factor in IBD Best Practice in Research. Clinical Gastroenterology 17 1 2003 105-117
69. Waetzig G.H. Schreiber S. Mitogen-activated protein kinases in chronic intestinal inflammation-targeting ancient pathways to treat modern diseases Alimentary and Pharmacological Therapeutics 18 1 2003 17-32
70. Schandene L. Vandenbussche P. Crusiaux A. et al. Differential effects of pentoxifylline on the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by monocytes and T cells Immunology 76 1 1992 30-34
71. Neuner P. Klosner G. Schauer E. et al. Pentoxifylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha by human peripheral blood mononuclear cells Immunology 83 2 1994 262-267
72. Bauditz J. Haemling J. Ortner M. et al. Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease Gut 40 4 1997 470-474
73. Vasiliauskas E.A. Kam L.Y. Abreu-Martin M.T. et al. An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn's disease Gastroenterology 117 6 1999 1278-1287
74. Ehrenpreis E.D. Kane S.V. Cohen L.B. et al. Thalidomide therapy for patients with refractory Crohn's disease: an open-label trial Gastroenterology 117 6 1999 1271-1277
75. Hommes D. van den Blink B. Plasse T. et al. Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease Gastroenterology 122 1 2002 7-14
76. Neurath M.F. Pettersson S. Meyer zum Buschenfelde K.H. Strober W. Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice Nature Medicine 2 9 1996 998-1004
77. Moreland L.W. Schiff M.H. Baumgartner S.W. et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial Annals of Internal Medicine 130 6 1999 478-486
78. Sandborn W.J. Hanauer S.B. Katz S. et al. Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial Gastroenterology 121 5 2001 1088-1094
79. Present D.H. Rutgeerts P. Targan S. et al. Infliximab for the treatment of fistulas in patients with Crohn's disease New England Journal of Medicine 340 18 1999 1398-1405
80. Rutgeerts P. D'Haens G. Targan S. et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease Gastroenterology 117 4 1999 761-769
81. D'Haens G. van Deventer S. van Hogezand R. et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: a European multicenter trial Gastroenterology 116 5 1999 1029-1034
82. Nikolaus S. Raedler A. Kuhbacker T. et al. Mechanisms in failure of infliximab for Crohn's disease Lancet 356 9240 2000 1475-1479
83. Hanauer S.B. Feagan B.G. Lichtenstein G.R. et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial Lancet 359 9317 2002 1541-1549
84. Van den Brande J.M. Braat H. van den Brink G.R. et al. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease Gastroenterology 124 7 2003 1774-1785
85. Lugering A. Schmidt M. Lugering N. et al. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway Gastroenterology 121 5 2001 1145-1157
86. Schaible T.F. Long term safety of infliximab Canadian Journal of Gastroenterology 14 supplement C 2000 29C-32C
87. Baert F. Noman M. Vermeire S. et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease New England Journal of Medicine 348 7 2003 601-608
88. Lim W.S. Powell R.J. Johnston I.D. Tuberculosis and treatment with infliximab New England Journal of Medicine 346 8 2002 623-626
89. Bickston S.J. Lichtenstein G.R. Arsenau K.O. et al. The relationship between infliximab treatment and lymphoma in Crohn's disease Gastroenterology 117 1999 1433-1437
90. Taylor K.D. Plevy S.E. Yang H. et al. ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn's disease Gastroenterology 120 6 2001 1347-1355
91. Esters N. Vermeire S. Joossens S. et al. Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease American Journal of Gastroenterology 97 6 2002 1458-1462
92. Schreiber S. Kuehbacher T. Mascheretti S. et al. Clinical efficacy of treatment with infliximab in a German multicenter, prospective, open-label trial in refractory Crohn's disease Gastroenterology 118 2000 A2970
93. Mascheretti S. Hampe J. Kuhbacher T. et al. Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with chronic active Crohn's disease treated with infliximab Pharmacogenomics Journal 2 2 2002 127-136
94. Louis E. Vermeire S. Rutgeerts P. et al. A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism Scandinavian Journal of Gastroenterology 37 7 2002 818-824
95. Vermeire S. Louis E. Carbonez A. et al. Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn's disease American Journal of Gastroenterology 97 9 2002 2357-2363
96. Butcher E.C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity Cell 67 6 1991 1033-1036
97. Yacyshyn B.R. Bowen-Yacyshyn M. et al. A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease Gastroenterology 114 1998 1133-1142
98. Schreiber S. Nikolaus S. Malchow H. et al. Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease Gastroenterology 120 6 2001 1339-1346
99. Yacyshyn B.R. Chey W.Y. Goff J. et al. Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn's disease Gut 51 1 2002 30-36
100. van Deventer S.J. Elson C.O. Fedorak R.N. Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group Gastroenterology 113 2 1997 383-389
101. Fedorak R.N. Gangl A. Elson C.O. et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group Gastroenterology 119 6 2000 1473-1482
102. Schreiber S. Fedorak R.N. Nielsen O.H. et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group Gastroenterology 119 6 2000 1461-1472
103. Gordon F.H. Hamilton M.I. Donoghue S. et al. A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha-4 integrin Alimentary and Pharmacological Therapeutics 16 4 2002 699-705
104. Gordon F.H. Lai C.W. Hamilton M.I. et al. A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn's disease Gastroenterology 121 2 2001 268-274
105. Ghosh S. Goldin E. Gordon F.H. et al. Natalizumab for active Crohn's disease New England Journal of Medicine 348 1 2003 24-32
106. Ogura Y. Inohara N. Benito A. et al. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB Journal of Biological Chemistry 276 7 2001 4812-4818