Immunity and inflammation:Inflammation

Immunogenetics of chronic inflammatory and autoimmune diseases

Crusius JBA1, Bouma G2,6, Morré SA1, Borm ME1, ZwiersA1, Karimi O1, van Bodegraven AA2, Hadithi M2, Mulder CJJ2, Wijmenga C3, van der Horst-Bruinsma IE4, van der Paardt M4,Dijkmans BAC4, Uitdehaag BMJ5, Hooper-van Veen T5, Schrijver HM5, Polman CH5, Peña AS1,2

1Laboratory of Immunogenetics, 2Gastroenterology, Depts. of 3Medical Genetics, University Medical Center Utrecht, Utrecht,4Rheumatology, 5Neurology, VU University Medical Center,6 Internal Medicine Slotervaart Hospital Amsterdam

Grant (Crohn’s and Colitis Foundation of America 2001-2003)

We investigate the immunogenetics of chronic inflammatory and autoimmune diseases to gain insight into the susceptibility to, severity of, and clinical course of these diseases in order to assess prognostic factors. Ongoing research includes the following disease models: inflammatory bowel disease, coeliac disease, multiple sclerosis, and ankylosing spondylitis. Both genetic epidemiological and functional studies are used in well-defined clinical cohorts as compared to control population to further unravel the complex genetic basis of these diseases. In addition, animal models are used for the genetic analysis of experimental colitis and the translation of the results generated in these models will be used for understanding the complex genetic susceptibility to human inflammatory bowel disease. In coeliac disease, HLA-DQ and other immunologically relevant gene polymorphisms are studied in relation to susceptibility, severity and refractoriness in patients and their families. We are also evaluating the safety and efficacy of VSL#3 (probiotics) in arthralgia in patients with quiescent IBD.

Publications:

(DI)T. Hooper-van Veen.Candidate gene studies in multiple sclerosis. VU University Medical Center.Promotores: Prof C.H. Polman, MD, PhD, Prof A.S. Peña, MD, PhD, FRCP, Co-promotor: B. M. J. Uitdehaag, MD, PhD.Reprografie VU, Amsterdam, 2003: 141p. (cat. A).

(WI)Gasche C, Alizadeh BZ, Peña AS.Genotype-phenotype correlations: how many disorders constitute inflammatory bowel disease?  Review in depth.Europ J Gastroenterol & Hepatol juni 2003;15:1-8.

(WI)Bayley JP, Baggen JM, Van de Pouw-Kraan T, Crusius JBA, Huizinga TWJ, Verweij CL.

Association between polymorphisms in the human chemokine receptor genes CCR2 and CX3CR1 and rheumatoid arthritis. Tissue Antigens 2003;62(2):170-174.

(WI)Bouma G, Seegers D, Borm ME, van Belzen MJ, Mulder CJ, Bailing J, Crusius JB, Meijer JW, Wijmenga C. IL12B and IRF1 gene polymorphisms and susceptibility to celiac disease.Eur J Immunogenet 2003;30:421-5.

(WI)Bouma G and Strober W. The Immunological and genetic basis of inflammatory Bowel Disease. Nature Reviews Immunology2003 Jul;3(7):521-33.

(WI)de Vries B, R. van Beem, MAJM Jacobs, BMJ Uitdehaag, AS Peña.The concurrence of inflammatory bowel disease and multiple sclerosis Rev Esp Enf Dig (Madrid) 2003;95; N.° Extraordinario, pp. 120-125

(WI)Karimi O, Peña AS.Probiotics: Isolated bacteria strain or mixtures of different strains? Two different approaches in the use of probiotics as therapeutics. Drugs of Today 2003, vol. 39 (8): 565-597

(WI)Mendoza JL, García-Paredes J, Peña AS, Cruz-Santamaría DM, Iglesias C, Díaz-Rubio M.

A continuous spectrum of neutrophilic dermatoses in Crohn’s disease. Rev Esp Enf Digest 2003;95:233-236

(WI)Murillo LS, Morré SA, Peña AS.The role of the CARD15 gene in the pathogenesis of Crohn’s disease: phenotypic classification and prognostic implications. Scandinavian Journal of Gastroenterology 2003, 38 (11): 1107-14.

(WI)Peña AS.Genetics of Inflammatory Bowel Disease- Past, Present and Future. Digestive Diseases 2003, 21:85-90.

(WI)Peña AS (Editorial). The value of serological and genetic markers in inflammatory bowel disease; Strength and weakness of the studies

Rev Esp Enf Dig (Madrid) 2003;95 (11); 752-754.

(WI)Peña AS.(Editorial).Change and progress in IBD.Rev Esp Enf Dig (Madrid) 2003;95; N.° Extraordinario, pp. 65-67

(WI)Peñate M, Cruz-Santamaría M, Mendoza JL, Peña AS, Díaz-Rubio M, García-Paredes J.

Optimización en el tratamiento de formas complicadas de la enfermedad inflamatoria intestinal. Enfermedad de Crohn fistulizante. An Med Interna (Madrid) 2003; 20: 37-45.

(WI)Schrijver HM., van As J., Crusius JBA, Dijkstra CD and Uitdehaag BMJ.IL1 gene polymorphisms: relevance of disease severity associated alleles with IL1-ß and IL-1ra production in multiple sclerosis. Mediators of Inflammation, 12 (2), April 2003, pag. 89-94.

(WI)Van Bodegraven AA, Pena AS.Treatment of Extraintestinal Manifestations in Inflammatory Bowel Disease.Curr Treat Options Gastroenterol 2003;6:201-12.

(WI)van der Paardt M, Crusius JBA, de Koning MHMT, Murillo LS, van de Stadt RJ, Dijkmans BAC, Peña AS, van der Horst-Bruinsma IE.CARD15 gene mutations are not associated with ankylosing spondylitis. Genes and Immunity 2003;4:77-78.

(WI)van Veen T, Crusius JBA, van Winsen L, Xia B, Barkhof F, Peña AS, Polman CH, Uitdehaag BMJ. CTLA-4 and CD28 gene polymorphisms in susceptibility, clinical course and progression of multiple sclerosis. J Neuroimmunol 2003; 140 (1-2): 188-193.

(WI)van Veen T, Schrijver HM, Zwiers A, Crusius JBA, Knol DL, Kalkers NF, Laine ML, Barkhof F, Peña AS, Polman CH, Uitdehaag BMJ. The interleukin-1 gene family in multiple sclerosis susceptibility and disease course. Multiple Sclerosis 2003: 9: 535-539.

(WI)van Veen T, N.F. Kalkers, J.B.A. Crusius, L. van Winsen, F. Barkhof, A.S. Peña, C.H. Polman, B.M.J. Uitdehaag. aB-crystallin genotype has impact on the multiple sclerosis phenotype. Neurology 2003;61:1245-1249.

(WI)Xia B, Crusius JBA, Wu J, Zwiers A, van Bodegraven AA, Peña AS. STAT6 Gene G2964A Polymorphism and Inflammatory Bowel Disease. Clin Exp Immunol 2003;131:446-450