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Blood, 15 January 2005, Vol. 105, No. 2, pp. 511-517. Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2003-12-4359. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4359v1 105/2/511    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Andersen, P. Articles by Barington, T. Search for Related Content PubMed PubMed Citation Articles by Andersen, P. Articles by Barington, T. Related Collections Immunobiology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Deficiency of somatic hypermutation of the antibody light chain is associated with increased frequency of severe respiratory tract infection in common variable immunodeficiency Pernille Andersen, Henrik Permin, Vagn Andersen, Lone Schejbel, Peter Garred, Arne Svejgaard, and Torben Barington From the Departments of Clinical Immunology and Infectious Diseases, University Hospital, Copenhagen, Denmark; Department of Internal Medicine, Bispebjerg Hospital, Copenhagen, Denmark; Department of Medicine TA and Institute for Inflammation Research, University Hospital, Copenhagen, Denmark; and Department of Clinical Immunology, Odense University Hospital, Odense, Denmark. Reduced levels of somatic hypermutation (SHM) have recently been described in IgG-switched immunoglobulin genes in a minority of patients with common variable immunodeficiency (CVID), demonstrating a disruption of the normal linkage between isotype switch and SHM. To see if, irrespective of isotype, there is a tendency to use unmutated immunoglobulin genes in CVID, we studied SHM in light-chain transcripts using a VA27-specific restriction enzyme-based hot-spot mutation assay (IgREHMA). Hot-spot mutations were found in 48% (median; reference interval, 28%-62%) of transcripts from 53 healthy controls. Values were significantly lower in 31 patients (median, 7.5%; range, 0%-73%; P < .0000001) of whom 24 (77%) had levels below the reference interval. Low levels of SHM correlated with increased frequency of severe respiratory tract infection (SRTI; P < .005), but not with diarrhea (P = .8). Mannose-binding lectin (MBL) deficiency also correlated with SRTI score (P = .009). However, the correlation of SHM and SRTI was also seen when only patients with normal MBL genotypes were analyzed (n = 18, P = .006). A slight decline of mutated fractions over years was noted (P = .01). This suggests that most patients with CVID fail to recruit affinity-maturated B cells, adding a qualitative deficiency to the quantitative deficiency characterizing these patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. C. van Zelm, T. Szczepanski, M. van der Burg, and J. J.M. van Dongen Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion J. Exp. Med., March 19, 2007; 204(3): 645 - 655. [Abstract] [Full Text] [PDF] L. Schejbel and P. Garred Primary Immunodeficiency: Complex Genetic Disorders? Clin. Chem., February 1, 2007; 53(2): 159 - 160. [Full Text] [PDF] C. Cunningham-Rundles, L. Radigan, A. K. Knight, L. Zhang, L. Bauer, and A. Nakazawa TLR9 Activation Is Defective in Common Variable Immune Deficiency J. Immunol., February 1, 2006; 176(3): 1978 - 1987. [Abstract] [Full Text] [PDF]

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