The presentation and natural history of immunodeficiency caused by nuclear factor κB essential modulator mutation Jordan S Orange, MD, PhD, Ashish Jain,

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The presentation and natural history of immunodeficiency caused by nuclear factor κB essential modulator mutation Jordan S Orange, MD, PhD, Ashish Jain, MD, Zuhair K Ballas, MD, Lynda C Schneider, MD, Raif S Geha, MD, Francisco A Bonilla, MD, PhD Journal of Allergy and Clinical Immunology Volume 113, Issue 4, Pages 725-733 (April 2004) DOI: 10.1016/j.jaci.2004.01.762

Fig 1 Facies of boys with ED-ID and a NEMO mutation. Patients 1 (A), 4 (B), 6 (C), and 7 (D) demonstrate many typical features of ED, including hypotrichosis, pale skin, depressed nasal bridge, frontal bossing, conical incisors, and oligodontia. Dental features are prominent, as seen in a magnified oral view of patient 3 (E) and a dental radiograph from patient 2 (F). Journal of Allergy and Clinical Immunology 2004 113, 725-733DOI: (10.1016/j.jaci.2004.01.762)

Fig 2 Summary of NEMO mutations in 7 patients with NEMO-ID. NEMO sequence alterations are listed above a schematic of the NEMO protein, with a line directed to the approximate location in the protein that is affected. αH, Alpha helix; C-C1, first coiled-coil domain; C-C2, second coiled-coil domain; LZ, leucine zipper; ZF, zinc finger. The nucleotide change is listed for the cDNA. The amino acid sequence for affected regions is enlarged beneath the appropriate regions of the NEMO schematic, and predicted residue alterations are demonstrated with an arrow. In the case of patient 5, the mutation affected exon 9, which is deleted (del) because of splice site alteration occurring upstream of nucleotide position 1056. Journal of Allergy and Clinical Immunology 2004 113, 725-733DOI: (10.1016/j.jaci.2004.01.762)

Fig 3 Serum immunoglobulin concentrations in patients with NEMO-ID. Serum IgG (left panel), IgM (middle panel), and IgA (right panel) concentrations were measured at presentation and over time. Each individual patient is denoted by a specific color, as shown in the legend in the middle panel. The dashed black lines mark the 5th and 95th percentile limits for age. IgG levels were plotted until the patients were started on intravenous immunoglobulin therapy and not thereafter. Journal of Allergy and Clinical Immunology 2004 113, 725-733DOI: (10.1016/j.jaci.2004.01.762)

Fig 4 Lymphocyte and humoral immune function in patients with NEMO-ID. A, Serum tetanus-specific IgG level is shown relative to the level considered to be protective (dashed line). Patients with undetectable levels are shown beneath the solid line. Initial assessments of PHA-, pokeweed mitogen (PMA)–, and concanavalin-A– (CONA)(B), as well as tetanus- and diphtheria-induced proliferation (C), are shown for each patient and expressed as stimulation indices. D, NK cell cytotoxicity was measured in patients who were alive at the time of this report as K562 lytic units. Patient NK cell activity (left, colored circles) is compared with that in 10 healthy control donors (right, black circles). All patient values are represented with colored circles according to the legend, and values are shown as means±SDs. The age-normalized 5th and 95th percentiles for the parameters provided in Fig 4, B and C, are approximated with gray bars, and when the 95th percentile value is greater than the graph scale, the value is shown within the bar. Journal of Allergy and Clinical Immunology 2004 113, 725-733DOI: (10.1016/j.jaci.2004.01.762)

Fig 5 Leukocyte counts and lymphocyte subsets in patients with NEMO-ID. Numbers of total WBCs and the absolute lymphocyte count (ALC; left panel), as well as specific lymphocyte subsets (middle panel) per milliliter of peripheral blood, were determined at the time of initial immunologic evaluation. Lymphocyte subpopulations as a proportion of total lymphocytes are also shown (right panel). The lymphocyte subtypes evaluated are presented on the x axis and include CD3+ T cells, CD3+/CD4+ T cells, CD8+/CD3+ T cells, CD3−/CD16+/CD56+ NK cells and CD3−/CD19+ B cells. Individual patient values are represented by colored circles as per the legend, and values are shown as means±SDs. The age-normalized 5th and 95th percentiles for the parameters provided are approximated with gray bars. Journal of Allergy and Clinical Immunology 2004 113, 725-733DOI: (10.1016/j.jaci.2004.01.762)

Fig 6 Alterations in lymphocyte subsets over time in patients with NEMO-ID. Total CD3+ T cells (left), CD3+/CD4+ T cells, and CD3+/CD8+ T cells are shown as a percentage of total lymphocytes over time. Individual patient values are represented by colored circles connected with a line of the same color as per the legend. The lower and upper dashed lines show age-related limits of the 5th and 95th percentile, respectively. Journal of Allergy and Clinical Immunology 2004 113, 725-733DOI: (10.1016/j.jaci.2004.01.762)