Cathelicidin deficiency predisposes to eczema herpeticum - 17/08/11
Reprint requests: Donald Y. M. Leung, MD, PhD, National Jewish Medical and Research Center, 1400 Jackson St, Room K926i, Denver, CO 80206Denver, Colo, Munich, Germany, and San Diego, Calif
Abstract |
Background |
The cathelicidin family of antimicrobial peptides is an integral component of the innate immune response that exhibits activity against bacterial, fungal, and viral pathogens. Eczema herpeticum (ADEH) develops in a subset of patients with atopic dermatitis (AD) because of disseminated infection with herpes simplex virus (HSV).
Objective |
This study investigated the potential role of cathelicidins in host susceptibility to HSV infection.
Methods |
Glycoprotein D was measured by means of real-time RT-PCR as a marker of HSV replication in skin biopsy specimens and human keratinocyte cultures. Cathelicidin expression was evaluated in skin biopsy specimens from patients with AD (n = 10) without a history of HSV skin infection and from patients with ADEH (n = 10).
Results |
The cathelicidin peptide LL-37 (human cathelicidin) exhibited activity against HSV in an antiviral assay, with significant killing (P < .001) within the physiologic range. The importance of cathelicidins in antiviral skin host defense was confirmed by the observation of higher levels of HSV-2 replication in cathelicidin-deficient (Cnlp−/−) mouse skin (2.6 ± 0.5 pg HSV/pg GAPDH, P < .05) compared with that seen in skin from their wild-type counterparts (0.9 ± 0.3). Skin from patients with ADEH exhibited significantly (P < .05) lower levels of cathelicidin protein expression than skin from patients with AD. We also found a significant inverse correlation between cathelicidin expression and serum IgE levels (r2 = 0.46, P < .05) in patients with AD and patients with ADEH.
Conclusion |
This study demonstrates that the cathelicidin peptide LL-37 possesses antiviral activity against HSV and demonstrates the importance of variable skin expression of cathelicidins in controlling susceptibility to ADEH. Additionally, serum IgE levels might be a surrogate marker for innate immune function and serve as a biomarker for which patients with AD are susceptible to ADEH.
Clinical implications |
A deficiency of LL-37 might render patients with AD susceptible to ADEH. Therefore increasing production of skin LL-37 might prevent herpes infection in patients with AD.
Le texte complet de cet article est disponible en PDF.Key words : Antimicrobial peptides, herpes simplex virus, atopic dermatitis, eczema herpeticum
Abbreviations used : AD, ADEH, AMP, CRAMP, HSV, LL-37, MEM, MTT, pfu
Plan
| Supported in part by the National Institutes of Health National Research Service Award (T32 AI 07365) and AAAAI Fujisawa Skin Diseases Award (M.D.H.); NIH grants AI052453 and AR45676 and a VA Merit Award (R.L.G.); and NIH grants AR41256 and 5R21AR051634, NIH/NIAID contracts N01 AI40029 and N01 AI40030, General Clinical Research Center grant MO1 RR00051 from the Division of Research Resources, the Edelstein Family Chair in Pediatric Allergy and Immunology, and the University of Colorado Cancer Center (D.Y.M.L.). Disclosure of potential conflict of interest: R. Gallo has consultant arrangements with Ceragenix. M. Boguniewicz has received grants from Novartis and Astellas and is lecture honoraria for Novartis and Astellas. All other authors—none disclosed. |
Vol 117 - N° 4
P. 836-841 - avril 2006 Retour au numéro
Article précédent
- Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease
- Jaclyn Smith, Emily Owen, John Earis, Ashley Woodcock
- Skin prick test to egg white provides additional diagnostic utility to serum egg white–specific IgE antibody concentration in children
- Adina Kay Knight, Wayne G. Shreffler, Hugh A. Sampson, Scott H. Sicherer, Sally Noone, Shideh Mofidi, Anna Nowak-Wegrzyn
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?