SEARCH:   Advanced

Blood, 15 February 2004, Vol. 103, No. 4, pp. 1376-1382. Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-05-1748. This Article Full Text (PDF) All Versions of this Article: 2003-05-1748v1 103/4/1376    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chiocchetti, A. Articles by Dianzani, U. Search for Related Content PubMed PubMed Citation Articles by Chiocchetti, A. Articles by Dianzani, U. Social Bookmarking                   What's this? Submitted June 3, 2003 Accepted August 3, 2003 High levels of osteopontin associated to polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation Annalisa Chiocchetti, Manuela Indelicato, Thea Bensi, Riccardo Mesturini, Mara Giordano, Selina Sametti, Luca Castelli, Flavia Bottarel, Maria Clorinda Mazzarino, Letizia Garbarini, Francesca Giacopelli, Guido Valesini, Claudio Santoro, Irma Dianzani, Ugo Ramenghi, and Umberto Dianzani* Department of Medical Science and IRCAD, University of Eastern Piedmont, Novara, Italy Department of Biomedical Science, University of Catania, Catania, Italy Department of Pediatrics, University of Turin, Turin, Italy Department of Pediatrics and CEBR, University of Genoa, Genoa, Italy Department of Medical Therapy, University of Rome, Rome, Italy * Corresponding author; email: dianzani{at}med.unipmn.it. The autoimmune/lymphoproliferative syndrome (ALPS) displays defective function of Fas, autoimmunities, lymphadenopathy/splenomegaly, expansion of CD4/CD8 double-negative (DN) T-cells. Dianzani's autoimmune/lymphoproliferative disease (DALD) is an ALPS variant lacking DN cells. Both forms have been ascribed to inherited mutations hitting the Fas system, but other factors may be involved. A pilot cDNA array analysis on a DALD patient detected overexpression of the cytokine osteopontin (OPN). This observation was confirmed by ELISA detection of higher OPN serum levels in DALD patients (n=25) than in controls (n=50). Analysis of the OPN cDNA identified four polymorphisms forming three haplotypes (A, B, and C). Their overall distribution and genotypic combinations were different in patients (n=26) and controls (n=158) (p<0.01). Subjects carrying haplotype-B and/or -C had a 8-fold higher risk of developing DALD than haplotype-A homozygotes. Several data suggest that these haplotypes influence OPN levels: 1) in DALD families, high levels co-segregated with haplotype-B or -C; 2) in healthy controls, haplotype-B or -C carriers displayed higher levels than haplotype-A homozygotes; 3) in AB and AC heterozygotes, mRNA for haplotype-B or -C was more abundant than that for haplotype-A. In vitro, exogenous OPN decreased activation-induced T-cell death, which suggests that high OPN levels are involved in the apoptosis defect. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. D. Shin, B. L. Park, H. S. Cheong, J.-H. Yoon, Y. J. Kim, and H.-S. Lee SPP1 polymorphisms associated with HBV clearance and HCC occurrence Int. J. Epidemiol., October 1, 2007; 36(5): 1001 - 1008. [Abstract] [Full Text] [PDF] M. Shaheen and N. L. Weintraub Osteopontin: A Bona Fide Mediator of Abdominal Aortic Aneurysm? Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 439 - 441. [Full Text] [PDF] J. Golledge, J. Muller, N. Shephard, P. Clancy, L. Smallwood, C. Moran, A. E. Dear, L. J. Palmer, and P. E. Norman Association Between Osteopontin and Human Abdominal Aortic Aneurysm Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 655 - 660. [Abstract] [Full Text] [PDF] R. Clementi, A. Chiocchetti, G. Cappellano, E. Cerutti, M. Ferretti, E. Orilieri, I. Dianzani, M. Ferrarini, M. Bregni, C. Danesino, et al. Variations of the perforin gene in patients with autoimmunity/lymphoproliferation and defective Fas function Blood, November 1, 2006; 108(9): 3079 - 3084. [Abstract] [Full Text] [PDF] J. Larkin, G. J. Renukaradhya, V. Sriram, W. Du, J. Gervay-Hague, and R. R. Brutkiewicz CD44 Differentially Activates Mouse NK T Cells and Conventional T Cells J. Immunol., July 1, 2006; 177(1): 268 - 279. [Abstract] [Full Text] [PDF] R Marciano, F Giacopelli, M T Divizia, M Gattorno, E Felici, A Pistorio, A Martini, R Ravazzolo, and P Picco A polymorphic variant inside the osteopontin gene shows association with disease course in oligoarticular juvenile idiopathic arthritis Ann Rheum Dis, May 1, 2006; 65(5): 662 - 665. [Abstract] [Full Text] [PDF] B. Abel, S. Freigang, M. F. Bachmann, U. Boschert, and M. Kopf Osteopontin Is Not Required for the Development of Th1 Responses and Viral Immunity J. Immunol., November 1, 2005; 175(9): 6006 - 6013. [Abstract] [Full Text] [PDF] C. K. Wong, L. C. W. Lit, L. S. Tam, E. K. Li, and C. W. K. Lam Elevation of plasma osteopontin concentration is correlated with disease activity in patients with systemic lupus erythematosus Rheumatology, May 1, 2005; 44(5): 602 - 606. [Abstract] [Full Text] [PDF] K. Kawamura, K. Iyonaga, H. Ichiyasu, J. Nagano, M. Suga, and Y. Sasaki Differentiation, Maturation, and Survival of Dendritic Cells by Osteopontin Regulation Clin. Vaccine Immunol., January 1, 2005; 12(1): 206 - 212. [Abstract] [Full Text] [PDF] F. Giacopelli, R. Marciano, A. Pistorio, P. Catarsi, S. Canini, G. Karsenty, and R. Ravazzolo Polymorphisms in the osteopontin promoter affect its transcriptional activity Physiol Genomics, December 15, 2004; 20(1): 87 - 96. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020