Comèl-Netherton syndrome defined as primary immunodeficiency
Ellen D Renner1, Dominik Hartl, Stacey Rylaarsdam
1Dr v Haunersches Kinderspital, Ludwig-Maximilians-Universität, Munich, Germany.
The Journal of Allergy and Clinical Immunology
|August 18, 2009
Summary
Comèl-Netherton syndrome, caused by SPINK5 mutations, involves immunodeficiency affecting both adaptive and innate immunity. Intravenous immunoglobulin therapy showed significant clinical improvement in patients.
Area of Science:
- Immunology
- Genetics
- Dermatology
Background:
- Comèl-Netherton syndrome (CNS) results from SPINK5 mutations, affecting lympho-epithelial Kazal-type 5 inhibitor (LEKTI) production.
- CNS is characterized by ichthyosis, bamboo hair, and atopic diathesis, with frequent infections but uninvestigated immunocompetence.
Purpose of the Study:
- To classify CNS as a primary immunodeficiency disorder.
- To evaluate the efficacy of intravenous immunoglobulin (IVIG) replacement therapy for CNS.
Main Methods:
- Sequenced SPINK5 and analyzed LEKTI expression in 9 CNS patients.
- Assessed immune function, including cognate immunity, cytokine profiles, and NK cell activity.
Main Results:
- Patients exhibited recurrent infections (skin, respiratory, GI) and failure to thrive.
- Identified SPINK5 mutations and decreased/absent LEKTI; revealed reduced memory B cells, impaired vaccine responses, skewed T(h)1 phenotype, and decreased NK cell cytotoxicity.
- IVIG treatment led to clinical improvement and temporary enhancement of NK cell function.
Conclusions:
- CNS involves epithelial LEKTI deficiency, leading to combined innate and adaptive immunodeficiency.
- IVIG therapy is a beneficial treatment for the immunologic complications of CNS.
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