|
|
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.
 Previous Article | Next Article 
Submitted December 22, 2003
Accepted August 30, 2004
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
Dept. of Clinical Immunology, University Hospital, Copenhagen, Denmark
Dept. of Infectious Diseases, University Hospital, Copenhagen, Denmark; Dept. of Internal Medicine, Bispebjerg Hospital, Copenhagen, Denmark
Dept. of Medicine TA and Institute for Inflammation Research, University Hospital, Copenhagen, Denmark
Dept. of Clinical Immunology, University Hospital, Copenhagen, Denmark; Dept. of Clinical Immunology, Odense University Hospital, Odense, Denmark
* Corresponding author; email: pernille.andersen{at}dadlnet.dk.
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 there, irrespective of isotype, is a tendency to utilize unmutated immunoglobulin genes in CVID, we studied SHM in kappa light chain transcripts using a V A27-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<0.0000001) 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<0.005), but not with diarrhea (P=0.8). Mannose binding lectin (MBL) deficiency also correlated with SRTI score (P=0.009). However, the correlation of SHM and SRTI was also seen when only patients with normal MBL genotypes were analyzed (N = 18, P = 0.006). A slight decline of mutated fractions over years was noted (P = 0.01).
This suggests that most CVID patients 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. Rakhmanov, B. Keller, S. Gutenberger, C. Foerster, M. Hoenig, G. Driessen, M. van der Burg, J. J. van Dongen, E. Wiech, M. Visentini, et al.
Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells
PNAS,
August 11, 2009;
106(32):
13451 - 13456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
