NDLI: Comèl-Netherton syndrome defined as primary immunodeficiency.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Renner, Ellen D. Hartl, Dominik Rylaarsdam, Stacey Young, Marguerite L. Monaco-Shawver, Linda Kleiner, Gary Markert, M. Louise Stiehm, E. Richard Belohradsky, Bernd H. Upton, Melissa P. Torgerson, Troy R. Orange, Jordan S. Ochs, Hans D.
Description	Country affiliation: Germany Author Affiliation: Renner ED ( Dr v Haunersches Kinderspital, Ludwig-Maximilians-Universität, Munich, Germany.)
Abstract	BACKGROUND: Mutations in serine protease inhibitor Kazal-type 5 (SPINK5), encoding the serine protease inhibitor lympho-epithelial Kazal-type 5 related inhibitor (LEKTI), cause Comèl-Netherton syndrome, an autosomal-recessive disease characterized by congenital ichthyosis, bamboo hair, and atopic diathesis. Despite increased frequency of infections, the immunocompetence of patients with Comèl-Netherton syndrome has not been extensively investigated. OBJECTIVE: To define Comèl-Netherton syndrome as a primary immunodeficiency disorder and to explore the benefit of intravenous immunoglobulin replacement therapy. METHODS: We enrolled 9 patients with Comèl-Netherton syndrome, sequenced SPINK5, and analyzed LEKTI expression by immunohistochemistry. Immune function was assessed by measuring cognate immunity, serum cytokine levels, and natural killer cell cytotoxicity. RESULTS: All patients presented with recurrent skin infections caused predominantly by Staphylococcus aureus. All but 1 reported recurrent respiratory tract infections; 78% had sepsis and/or pneumonia; 67% had recurrent gastrointestinal disease and failure to thrive. Mutations in SPINK5-including 6 novel mutations-were identified in 8 patients. LEKTI expression was decreased or absent in all patients. Immunologic evaluation revealed reduced memory B cells and defective responses to vaccination with Pneumovax and bacteriophage phiX174, characterized by impaired antibody amplification and class-switching. Immune dysregulation was suggested by a skewed T(h)1 phenotype and elevated proinflammatory cytokine levels, whereas serum concentrations of the chemokine (C-C motif) ligand 5 and natural killer cell cytotoxicity were decreased. Treatment with intravenous immunoglobulin resulted in remarkable clinical improvement and temporarily increased natural killer cell cytotoxicity. CONCLUSION: These data provide new insights into the immunopathology of Comèl-Netherton syndrome and demonstrate that this multisystem disorder, characterized by lack of LEKTI expression in epithelial cells, is complicated by cognate and innate immunodeficiency that responds favorably to intravenous immunoglobulin therapy.
File Format	HTM / HTML
ISSN	00916749
e-ISSN	10976825
DOI	10.1016/j.jaci.2009.06.009
Journal	Journal of Allergy and Clinical Immunology
Issue Number	3
Volume Number	124
Language	English
Publisher	Elsevier
Publisher Date	2009-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Immunology Immunologic Deficiency Syndromes Genetics Immunology Proteinase Inhibitory Proteins, Secretory Staphylococcal Skin Infections Staphylococcus Aureus B-lymphocytes Metabolism Child, Preschool Cytokines Blood Immunoglobulins, Intravenous Therapeutic Use Drug Therapy Immunologic Factors Mutation Natural Killer T-cells Biosynthesis T-lymphocytes, Regulatory Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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