Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: Clinical and immunologic outcomes.

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Presentation transcript:

Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: Clinical and immunologic outcomes in heterozygotes Li Zhang, Lin Radigan, Ulrich Salzer, MD, Timothy W. Behrens, MD, Bodo Grimbacher, MD, George Diaz, MD, PhD, James Bussel, MD, Charlotte Cunningham-Rundles, MD, PhD Journal of Allergy and Clinical Immunology Volume 120, Issue 5, Pages 1178-1185 (November 2007) DOI: 10.1016/j.jaci.2007.10.001 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Heterozygous mutations may lead to reduced ligand binding. B cells (EBV cell lines) of subjects with TACI mutations indicated were tested to determine the binding of APRIL in comparison with the controls indicated. The mean fluorescence intensity (MFI, x-axis) for B cells (cell counts, y-axis) is shown. Isotype controls are marked in closed areas, surface APRIL fluorescence in open areas. NL, Normal. Journal of Allergy and Clinical Immunology 2007 120, 1178-1185DOI: (10.1016/j.jaci.2007.10.001) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 APRIL-induced proliferation of B cells. Cells were stained with CFSE (log scale, x-axis, wavelength, 492 nm) and cultured with indicated stimulators for 6 days; y-axis = cell counts. A and B, Non-B and nondividing cells = dense population at the lower right of each panel. The CD19+ B-cell population is indicated (top pink rectangle). C and D, CFSE-stained B-cell populations. Journal of Allergy and Clinical Immunology 2007 120, 1178-1185DOI: (10.1016/j.jaci.2007.10.001) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Proliferation of B cells of subjects with C104R TACI mutations. As for Fig 2, proliferation of CFSE (x-axis)–labeled B cells of 3 unrelated subjects with CVID with C104R mutations were compared by using stimulators shown. y-axis = cell counts. A, APRIL alone. B, APRIL + IL-10. C, CD40 ligand + IL-10. D, CpG. Journal of Allergy and Clinical Immunology 2007 120, 1178-1185DOI: (10.1016/j.jaci.2007.10.001) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 IgG and IgA production. Peripheral blood cells of subjects were cultured as shown to assess IgG (A) or IgA (B) production (ng/mL); values minus baseline levels. Four subjects with CVID (no mutations) and 8 subjects with the heterozygous mutations shown are compared or are indicated, ng/mL (y-axis). Results for 8 normal controls are given as means (± SEs). NL, Normal; Pt, patient. Journal of Allergy and Clinical Immunology 2007 120, 1178-1185DOI: (10.1016/j.jaci.2007.10.001) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Immunoglobulin production for normal relatives. As for Fig 4, peripheral blood cells of subjects (#3 C104R patient [Pt], and #10 C104R Pt 2) and their first-degree relatives with the same mutation (C104R Rel-1, C104R Rel-2) were tested for IgG (A) and IgA (B) production. The amounts of IgG or IgA over baseline are given in ng/mL (y-axis). The median (± SE) is shown for 8 normal controls. Journal of Allergy and Clinical Immunology 2007 120, 1178-1185DOI: (10.1016/j.jaci.2007.10.001) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions