title: Common variable immune deficiency in children--clinical characteristics varies depending on defect in peripheral B cell maturation.
abstract: Common variable immune deficiency (CVID) is a heterogeneous disease associated with ineffective production of antibodies. It is usually diagnosed in adulthood, but a variable proportion of children develop CVID. Early identification of patients with potentially worse prognosis may help to avoid serious complications. The goal of this study was to associate the clinical phenotype of patients with early onset CVID with peripheral B-cell maturation profile. Four color flow cytometry was used to define distribution of peripheral B-cell subsets in 49 children with early-onset CVID. All clinical data were extracted from medical records. A proportion of patients demonstrated diminishing with time total B-lymphocytes pool, beyond physiological age-related changes. Irrespective from duration of the follow-up period the B-cell maturation profile in individual patients remained unchanged. We identified six different aberrant peripheral B cell maturation profiles associated with different clinical characteristics. Patients with an early B-cell maturation block earlier required replacement therapy and were at significantly greater risk of enteropathy, granuloma formation, cytopenia, and lymphoproliferation. B-cell maturation inhibited at the natural effector stage was associated with higher risk of autoimmune manifestations other than autoimmune cytopenia. Prevalence of male patients was observed among patients with B-cell maturation inhibited at naïve B-cell stage. In conclusion, the diagnostic process in patients with suspected early-onset CVID shall include routine analysis of peripheral B-cell maturation to provide surrogate markers identifying patients at greater risk of developing certain complications.
authors: Histocompatibility Laboratory, Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland. b.piatosa@czd.pl
authors: Barbara
authors: B
authors: Piątosa
authors: Małgorzata
authors: M
authors: Pac
authors: Katarzyna
authors: K
authors: Siewiera
authors: Barbara
authors: B
authors: Pietrucha
authors: Maja
authors: M
authors: Klaudel-Dreszler
authors: Edyta
authors: E
authors: Heropolitańska-Pliszka
authors: Beata
authors: B
authors: Wolska-Kuśnierz
authors: Hanna
authors: H
authors: Dmeńska
authors: Hanna
authors: H
authors: Gregorek
authors: Irena
authors: I
authors: Sokolnicka
authors: Aneta
authors: A
authors: Rękawek
authors: Katarzyna
authors: K
authors: Tkaczyk
authors: Ewa
authors: E
authors: Bernatowska
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001775:Blood Circulation; D002454:Cell Differentiation; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D003955:Diagnostic Tests, Routine; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011379:Prognosis; D012306:Risk; D012737:Sex Factors
references: Clin Exp Immunol. 2000 May;120(2):225-31
references: 10792368
references: Int Arch Allergy Immunol. 2010;153(1):95-101
references: 20357490
references: J Clin Invest. 2010 Jan;120(1):214-22
references: 20038800
references: J Investig Allergol Clin Immunol. 2008;18(4):260-5
references: 18714533
references: An Pediatr (Barc). 2011 Feb;74(2):74-83
references: 21168377
references: Vaccine. 2011 May 31;29(24):4142-50
references: 21473955
references: Clin Immunol. 2008 Sep;128(3):314-21
references: 18620909
references: Clin Immunol. 2006 Sep;120(3):310-8
references: 16782407
references: J Allergy Clin Immunol. 2007 Oct;120(4):776-94
references: 17952897
references: J Clin Immunol. 2010 Sep;30(5):746-55
references: 20437084
references: J Immunol. 2005 Oct 15;175(8):5498-503
references: 16210658
references: Scand J Immunol. 2011 Nov;74(5):502-10
references: 21815909
references: Expert Rev Clin Immunol. 2009 Sep;5(5):557-64
references: 20477641
references: Blood. 2008 Jan 1;111(1):77-85
references: 17898316
references: Clin Immunol. 2010 Dec;137(3):374-83
references: 20851686
references: J Allergy Clin Immunol. 2004 Aug;114(2):415-21
references: 15316526
references: Clin Immunol. 2009 Nov;133(2):198-207
references: 19716342
references: Blood. 2008 Jul 15;112(2):277-86
references: 18319398
references: Clin Immunol. 1999 Dec;93(3):190-7
references: 10600329
references: Immunobiology. 2008;213(5):447-54
references: 18472053
references: Clin Immunol. 1999 Jul;92(1):34-48
references: 10413651
references: Pediatr Allergy Immunol. 2009 Nov;20(7):693-8
references: 19196447
references: J Autoimmun. 2005 Aug;25(1):57-62
references: 15994061
references: Int J Immunopathol Pharmacol. 2008 Apr-Jun;21(2):343-52
references: 18547478
references: Clin Infect Dis. 2008 May 15;46(10):1547-54
references: 18419489
references: J Clin Immunol. 2001 Mar;21(2):145-9
references: 11332653
references: Clin Immunol. 2002 Apr;103(1):34-42
references: 11987983
references: Clin Immunol. 2011 Mar;138(3):266-73
references: 21215701
references: Nat Immunol. 2010 Sep;11(9):836-45
references: 20676093
references: Clin Exp Immunol. 2011 Aug;165(2):235-42
references: 21635229
references: Ann Allergy Asthma Immunol. 2006 Nov;97(5):653-6
references: 17165275
references: Blood. 2011 Aug 25;118(8):2150-8
references: 21690558
references: J Allergy Clin Immunol. 2006 Apr;117(4):740-6; quiz 747
references: 16630927
references: Blood. 2011 Jul 14;118(2):309-18
references: 21576700
references: J Pediatr. 2009 Jun;154(6):888-94
references: 19230900
references: Pediatr Allergy Immunol. 2010 Aug;21(5):852-8
references: 20337966
references: J Allergy Clin Immunol. 2005 Feb;115(2):412-7
references: 15696104
references: Immunobiology. 2002 Dec;206(5):502-13
references: 12607725
references: J Clin Immunol. 2012 Feb;32(1):50-60
references: 22048980
references: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13451-6
references: 19666505
references: J Exp Med. 2004 Jan 5;199(1):91-8
references: 14707116
references: Autoimmun Rev. 2008 Feb;7(4):309-12
references: 18295735
references: Nat Rev Immunol. 2008 Jan;8(1):22-33
references: 18097447
references: Nature. 2001 Jan 4;409(6816):102-5
references: 11343122
references: J Allergy Clin Immunol. 2012 Mar;129(3):755-761.e7
references: 22130422
references: J Clin Pathol. 2005 May;58(5):546-7
references: 15858130
references: Cytometry A. 2009 Nov;75(11):902-9
references: 19802875
references: QJM. 2002 Oct;95(10):655-62
references: 12324637
references: Clin Immunol. 2009 Feb;130(2):199-212
references: 18977183
references: J Clin Immunol. 2003 Sep;23(5):385-400
references: 14601647
references: J Clin Invest. 2010 Apr;120(4):1265-74
references: 20237408
references: J Pediatr. 2003 Nov;143(5):662-5
references: 14615742
references: Blood. 2006 Apr 15;107(8):3045-52
references: 16384931
references: Genes Immun. 2010 Oct;11(7):523-30
references: 20445561
references: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13945-50
references: 19666484
references: Clin Immunol. 2010 Apr;135(1):63-71
references: 20006554
references: Arch Dis Child. 2003 Dec;88(12):1101-5
references: 14670780
references: J Immunol. 2010 Dec 1;185(11):6431-8
references: 21041728
references: Eur J Pediatr. 1999 Jan;158(1):29-31
references: 9950304
references: Cytometry B Clin Cytom. 2010 Nov;78(6):372-81
references: 20533385
references: J Immunol. 2010 Jun 15;184(12):7305-13
references: 20495065
references: Pediatr Allergy Immunol. 2009 Mar;20(2):113-8
references: 18798799
references: Blood. 2010 Jan 21;115(3):519-29
references: 19965666
references: Pediatr Radiol. 1997 Oct;27(10):794-8
references: 9323243
references: Clin Immunol. 2005 Jul;116(1):37-41
references: 15925830
references: Autoimmun Rev. 2006 Feb;5(2):156-9
references: 16431351
references: Blood. 2002 Mar 1;99(5):1544-51
references: 11861266
references: Pediatr Res. 2002 Feb;51(2):159-68
references: 11809909
references: N Engl J Med. 2006 May 4;354(18):1901-12
references: 16672701
references: J Immunol. 2006 Jun 1;176(11):7096-103
references: 16709872
references: Br J Haematol. 2009 Jun;145(6):709-27
references: 19344423
references: J Autoimmun. 2011 Feb;36(1):25-32
references: 21075598
references: Blood. 2011 Dec 22;118(26):6814-23
references: 22042693
references: Clin Immunol. 2009 Apr;131(1):50-9
references: 19162556
references: Chest. 2007 Jun;131(6):1883-9
references: 17400689
references: J Investig Allergol Clin Immunol. 2010;20(5):372-9
references: 20945602