Decreased CD21+and CD23+B-lymphocytes in Down syndrome children: association with decreased antibody production?

R.H.J. Verstegen, E.F.A. Gemen, J. de Jongh-Leuvenink, G.C.M. Kusters, E. de Vries

    Research output: Contribution to journalMeeting AbstractAcademic

    Abstract

    Introduction: Down Syndrome (DS) is associated with an increased incidence of respiratory infections, and antipolysaccharide antibody deficiency. Polysaccharides form a complex with complement C3d which binds to complement receptor type 2 (CD21) on B-lymphocytes, initiating a T-cell-independent antibody response. CD23, the low-affinity IgE-receptor (FcRII), is a ligand of CD21. Together, they stimulate B-lymphocyte proliferation and differentiation. CD23-expression is increased just before the class-switch from IgM to IgG, IgA or IgE. Besides, CD23 is involved in both positive and negative feedback-loops for IgE-homeostasis. Interestingly, both asthma incidence and IgE-production are decreased in DS. Aim: Is CD21- and/or CD23-expression on B-lymphocytes decreased in DS compared to age-matched controls (AMC)? Methods: After informed consent, subpopulations of CD19+ B-lymphocytes were determined in whole blood (EDTA) collected by planned venipuncture (DS) or leftover material (AMC) using three-color flow cytometry (BD FACScan) with directly labeled monoclonal antibodies at 915 month, 1524 month, 25 year, 510 year, 1016 year and ‡ 16 year, in n = 11, 9, 16, 38, 19, 3 DS and n = 1, 1, 10, 7, 8, 2 AMC for CD5/CD21/ CD19-subpopulations and in n = 8, 7, 7, 19, 13, 2 DS and n = 0, 1, 10, 7, 8, 2 AMC of these for CD23/CD19-subpopulations, respectively. Serum total IgE was measured using a sandwich chemiluminescent immunoassay (Immulite 2500DPC) in 45/56 DS in which CD23+ Blymphocyte subpopulations had been determined. The MannWhitney U test (two-tailed) was used to compare the percentages (medians) of lymphocyte subpopulations between DS and AMC. Correlations between total IgE, age and lymphocyte subpopulations were assessed using SPSS 15.0 for Windows. Results: The expression of CD21 on CD19+ B-lymphocytes in DS was decreased, more so within the CD5+/CD19+ subpopulation; there was no age-related change. Percentages of CD21++, CD21+ and CD21- cells within the CD5+/CD19+ B-lymphocyte subpopulation in DS were 66%, 27%, and 7% respectively (AMC: 90%, 7%, 3%; P < 0.001, P < 0.001, P = 0.004), and within CD5-/CD19+ B-lymphocytes 78%, 11% and 11% (AMC: 89%, 7%, 4%; all P < 0.001). Absolute numbers of CD21++ B-lymphocytes were decreased. The median percentage of CD23+ B-lymphocytes was decreased in DS and more variable than in AMC: 64.9% (range: 19.1100%) vs 82.1% (range: 58.099.3%) of CD19+ B-lymphocytes was CD23+ (P < 0.001). n = 33 DS had ‘normal’ percentages of CD23+ within the AMC-range (median 74.8%); n = 23 DS had percentages < 58.0% (median 45.2%). There was no correlation between age and expression of CD23+ for DS or AMC. Total IgE was increased (> 50 IU/L) in 8/45 (18%) DS, they all showed ‘normal’ CD23-expression. Absolute numbers of CD21+/++ and CD23+ B-lymphocytes were significantly correlated for both DS and AMC (r = 0.77, P < 0.001 and r = 0.96, P < 0.001, respectively). Discussion: CD21 has an important role in the response to capsular polysaccharide antigens. The lower numbers of CD21+/++ B-lymphocytes in DS may in part explain the increased frequency of respiratory tract infections and the decreased response to unconjugated pneumococcal vaccine. CD23-expression on CD19+ B-lymphocytes is variable in DS. Interestingly, we only found increased total IgE values in the ‘normal’ CD23+ group. Because of the important role of CD21-CD23-interaction in antibody production, our results could imply that DS children also differ in their ability to produce antibodies. This would fit in with the clinical experience showing variability in the burden of infections and respiratory symptoms in DS.
    Original languageEnglish
    Pages (from-to)151-151
    JournalClinical and Experimental Immunology
    Volume154
    Issue numberSuppl. 1
    DOIs
    Publication statusPublished - Nov 2008
    Event13th Biennial Meeting of the European Society for Immunodeficiencies, ESID 2008 - Theater aan de Parade, 's‐Hertogenbosch, Netherlands
    Duration: 16 Oct 200819 Oct 2008
    Conference number: 13

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