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Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity.
Allergy. 2011 Jul; 66(7):934-40.A

Abstract

BACKGROUND

Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity.

METHODS

The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population.

RESULTS

The levels of PCA, UCA and HIS correlated with FLG genotype. Furthermore, these levels were higher in the CTRL when compared to AD patients with no FLG mutations. Multiple regression analysis showed that NMF levels were independently associated with FLG genotype and severity of disease.

CONCLUSION

Decreased NMF is a global feature of moderate-to-severe AD; within AD, FLG genotype is the major determinant of NMF, with disease severity as a secondary modifier. NMF components are reliably determined by a noninvasive and relatively inexpensive tape stripping technique.

Authors+Show Affiliations

Coronel Institute of Occupational Health, Academic Medical Center, Amsterdam, the Netherlands. s.kezic@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21261659

Citation

Kezic, S, et al. "Levels of Filaggrin Degradation Products Are Influenced By Both Filaggrin Genotype and Atopic Dermatitis Severity." Allergy, vol. 66, no. 7, 2011, pp. 934-40.
Kezic S, O'Regan GM, Yau N, et al. Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy. 2011;66(7):934-40.
Kezic, S., O'Regan, G. M., Yau, N., Sandilands, A., Chen, H., Campbell, L. E., Kroboth, K., Watson, R., Rowland, M., McLean, W. H., & Irvine, A. D. (2011). Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy, 66(7), 934-40. https://doi.org/10.1111/j.1398-9995.2010.02540.x
Kezic S, et al. Levels of Filaggrin Degradation Products Are Influenced By Both Filaggrin Genotype and Atopic Dermatitis Severity. Allergy. 2011;66(7):934-40. PubMed PMID: 21261659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. AU - Kezic,S, AU - O'Regan,G M, AU - Yau,N, AU - Sandilands,A, AU - Chen,H, AU - Campbell,L E, AU - Kroboth,K, AU - Watson,R, AU - Rowland,M, AU - McLean,W H Irwin, AU - Irvine,A D, Y1 - 2011/01/25/ PY - 2011/1/26/entrez PY - 2011/1/26/pubmed PY - 2011/10/1/medline SP - 934 EP - 40 JF - Allergy JO - Allergy VL - 66 IS - 7 N2 - BACKGROUND: Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity. METHODS: The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population. RESULTS: The levels of PCA, UCA and HIS correlated with FLG genotype. Furthermore, these levels were higher in the CTRL when compared to AD patients with no FLG mutations. Multiple regression analysis showed that NMF levels were independently associated with FLG genotype and severity of disease. CONCLUSION: Decreased NMF is a global feature of moderate-to-severe AD; within AD, FLG genotype is the major determinant of NMF, with disease severity as a secondary modifier. NMF components are reliably determined by a noninvasive and relatively inexpensive tape stripping technique. SN - 1398-9995 UR - https://www.unboundmedicine.com/medline/citation/21261659/Levels_of_filaggrin_degradation_products_are_influenced_by_both_filaggrin_genotype_and_atopic_dermatitis_severity_ L2 - https://doi.org/10.1111/j.1398-9995.2010.02540.x DB - PRIME DP - Unbound Medicine ER -