Comèl-Netherton syndrome defined as primary immunodeficiency

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Presentation transcript:

Comèl-Netherton syndrome defined as primary immunodeficiency Ellen D. Renner, MD, Dominik Hartl, MD, Stacey Rylaarsdam, AAS, Marguerite L. Young, BS, Linda Monaco-Shawver, BA, Gary Kleiner, MD, M. Louise Markert, MD, E. Richard Stiehm, MD, Bernd H. Belohradsky, MD, Melissa P. Upton, MD, Troy R. Torgerson, MD, PhD, Jordan S. Orange, MD, PhD, Hans D. Ochs, MD Journal of Allergy and Clinical Immunology Volume 124, Issue 3, Pages 536-543 (September 2009) DOI: 10.1016/j.jaci.2009.06.009 Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Immunologic assessment of patients with Comèl-Netherton syndrome. A, Serum immunoglobulin levels measured before IVIG was started; arrows indicate 2 SD below (↓) or above (↑) age-matched control value.32 ∗Patient 3 had a serum IgE level of 1119 IU/mL (2 SD above age-matched controls) at 6 years of age. B, Decreased antibody responses after primary and secondary immunization with the neoantigen, bacteriophage phiX174, which was injected twice 6 weeks apart. Neutralizing antibody titers were determined in serially obtained serum samples and expressed as rate of phage inactivation or K value (Kv)22 plotted on a log scale (solid line in gray area, geometric mean and 95% confidence limit measured in 50 normal controls). The mean percentage of phage-specific IgG antibody in serum collected 2 weeks after the second immunization was identified as being resistant to treatment with 2-mercaptoethanol (2-ME; values of 50 normal controls, 48% ± 23% 1 SD). For patient 6, only 1 sample was collected after secondary immunization. C, NK-cell cytotoxicity of Ficoll-Hypaque–isolated PBMCs against K562 cells measured before IVIG treatment. The mean percent of lysis observed in at least 3 independent experiments performed in each of the 3 patients studied (solid line in gray area, mean and ± 2 SD measured in 18 normal controls). D, Median ± interquartile ranges of serum cytokine levels observed in 8 patients with Comèl-Netherton syndrome (filled columns) are compared with those of 16 age-matched normal controls (open columns); ∗P values <.01. Median values of IL-4, IL-5, IL-7, IL-13, IL-15, IL-17, INF-α, INF-γ, and monokine induced by INF-γ were below detection limit in the majority of patients and control subjects (data not shown). ID, (Patient) Identification; IL-1Ra, IL-1 receptor antagonist; sIL-2R, soluble IL-2 receptor. Journal of Allergy and Clinical Immunology 2009 124, 536-543DOI: (10.1016/j.jaci.2009.06.009) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Toddler (patient 5) with Comèl-Netherton syndrome before and 3 months after IVIG treatment. Journal of Allergy and Clinical Immunology 2009 124, 536-543DOI: (10.1016/j.jaci.2009.06.009) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Expression of LEKTI in different human tissues. Immunohistochemistry counterstained with hematoxylin shows LEKTI protein in red, if present. Buccal mucosal cells of a healthy individual (A) and patient 3 (B); skin biopsies of a healthy child with LEKTI expression in superficial epidermal squamous layer (C) and patient 4 (D) lacking LEKTI; LEKTI expression in Hassall corpuscles (E) and tonsillar crypts (F) of normal controls. Journal of Allergy and Clinical Immunology 2009 124, 536-543DOI: (10.1016/j.jaci.2009.06.009) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions