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Clinical Features of Patients with Filaggrin Gene Mutations in Childhood Atopic Dermatitis
AB260 Abstracts
845
Clinical Features of Patients with Filaggrin Gene Mutations in Childhood Atopic Dermatitis Ryuhei Yasuoka, MD1, Tatsuki Fukuie, MD, PhD1, Jun-ichi Sakabe, PhD2, Yoshiki Tokura, MD, PhD2, Tomohide Taguchi, MD1; 1 Department of Pediatrics, Hamamatsu University School of Medicine, Shizuoka, Japan, 2Department of Dermatology, Hamamatsu University School of Medicine, Shizuoka, Japan. RATIONALE: Filaggrin (FLG) gene mutation carriers have increased risk of atopic dermatitis (AD). Herein we describe the clinical features of Japanese children with AD with and without FLG-null mutations. METHODS: Children with moderate-to-severe AD whose parents consented to filaggrin gene mutation analysis during February 2009 to July 2014 were enrolled. Each child was genotyped for the eight most prevalent FLG-null mutations in the Japanese population (R501X, 3321delA, S1695X, S1701X, S2554X, S2889X, S3296X, and K4022X). We retrospectively investigated total IgE, specific IgE (house dust mite, cedar pollen, egg white, milk, and wheat), eosinophil count, serum TARC, SCORAD, and eczema onset age on first examination. RESULTS: Of the 95 children (2 months–13 years, median 11 months), 25 had FLG-null mutations (positive ratio 35.7%, 22 heterozygotes, three compound heterozygotes). Eczema onset age was earlier in children with FLG-null mutations than in wild type. In children >1 year old at initial examination, the egg, milk, and wheat-specific IgEs in patients with FLG-null mutation were significantly higher than in wild type (P50.004, P 5 0.044, P 5 0.040, Mann–Whitney U test). Among only the cases with FLG-null mutations, egg white, house dust mite, and pollen-specific IgEs at 2 years were significantly lower in the AD patients treated before 1 year of age, compared with those who had been treated between 1 and 2 years (P50.059, P50.015, P50.014,Mann–Whitney U test). CONCLUSIONS: Our study indicates that eczema onset was earlier in children with FLG-null mutations and specific IgEs were higher on delayed treatment. Even with FLG-null mutation, sensitization to allergens might be preventable by treating AD early.
846
TUESDAY
Duration of Breastfeeding Modulates the Effect of Filaggrin Variants on the Risk of Eczema Early in Life: Results from the Isle of Wight Birth Cohort Ali H. Ziyab, PhD1, Wilfried Karmaus, MD, DrMed, MPH2, Hongmei Zhang, PhD2, John W. Holloway, PhD3, Susan L. Ewart, DVM, PhD4, Syed H. Arshad, DM, FRCP5,6; 1Kuwait University, Kuwait, 2University of Memphis, Memphis, TN, 3University of Southampton, Southampton, United Kingdom, 4Michigan State University, East Lansing, MI, 5The David Hide Asthma and Allergy Research Centre, United Kingdom, 6University of Southampton, United Kingdom. RATIONALE: Filaggrin gene (FLG) variants are common risk factors for eczema development; whereas, breastfeeding has been suggested as a possible protective factor. We hypothesized that breastfeeding will be protective in those with FLG variants. Thus, with increasing duration of breastfeeding the risk of eczema early in life will become similar among those with and without FLG variants. METHODS: In the Isle of Wight birth cohort (n 5 1,456), information regarding eczema was collected at ages 1, 2, 4, 10, and 18 years. Information on duration of breastfeeding was obtained at 1 and/or 2 years follow-ups. FLG variants (R501X, 2282del4, and S3247X) were genotyped in 1,150 participants. Using log-binomial regression models, the interaction effect between FLG variants and duration of breastfeeding on the risk of eczema at 1 and 2 years was evaluated controlling for potential confounders. RESULTS: FLG variants increased the risk of eczema by 1.64-fold (Pvalue 5 0.009) during the first 2-years of life. Duration of breastfeeding did not show an independent association with eczema. However, a possible interaction effect was observed (RRInteraction 5 0.97, PInteraction 5 0.062). The effect of FLG variants on the risk of eczema decreased as the duration of breastfeeding increased (in the absence of breastfeeding: RR52.27, P-
J ALLERGY CLIN IMMUNOL FEBRUARY 2015
value 5 0.002; at 6-months of breastfeeding: RR 5 1.27, P-value 5 0.323). CONCLUSIONS: Duration of Breastfeeding attenuated the association between FLG variants and eczema in early life. The mechanism through which this effect modification works needs to be investigated.
847
Filaggrin Gene Polymorphism Pro478Ser, but Not Loss-ofFunction Mutations Mp.Arg501Ter or C.2282del4, Relates with Atopic Dermatitis Severity and Increased Staphylococcal aureus Colonization in Adult Patients Liliana Rocha1, Cristina Lopes, MD2,3, Susana Fernandes4, Oksana Sokhatska5, Jose Soares6, Freni Tavaria7, Manuela Pintado7, Andre M. Moreira, MD8,9, Luis Delgado, MD8,10; 1Genetics Departament, Faculty of Medicine, University of Porto, Portugal, Porto, Portugal, 2Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Portugal, Porto, Portugal, 3Allergy Unit, Pedro Hispano Hospital, Matosinhos, Portugal, 4Genetics Department Medical faculty Porto University, 5Immunology Laboratory, Medical Faculty, Porto University, 6Biology and Fine Chemistry Unit, Biotechnology Faculty, Catholic University, Porto, Portugal, 7Biology and Fine Chemistry Unit, Biotechnology Faculty, Catholic University, Portugal, 8Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Porto, Portugal, 9Allergy and Clinical Immunology Department, Centro Hospitalar S~ao Jo~ao, EPE, Porto, Portugal, 10 Immunology Lab, Department of Clinical Pathology, Porto, Portugal. RATIONALE: We aimed to assess the impact of filaggrin (FLG) gene mutations p.Arg501Ter, c.2282del4 and polymorphism p.Pro478Ser on disease severity, skin bacterial colonization, and allergy in Portuguese subjects with long term atopic dermatitis (AD). METHODS: In this cross sectional study, data from 73 patients, (30613 years, 61% female, 77% atopic) with AD for 16610 years was analyzed. Mutations were analyzed by PCR amplification of exon 3 of FLG gene and Sanger sequencing, disease severity trough SCORAD, allergy by serum levels of IgE, Phadiatop, eosinophil cationic protein and specific IgE to Staphylococcus aureus (SA) enterotoxin A, B, C , TSST and Malassezia spp. Number of colony forming units of staphylococci and SA species in 25 cm2 of poplitea, brachial ceases, interscapular regions were determined. Non-parametric statistic analyses and chi-square were used. RESULTS: FLG mutations p.Arg501Ter (n59) and c.2282del4 (n52) were identified in 14.8% patients and were not associated with AD severity, allergic or microbiological parameters; p.Pro478Ser polymorphism was present in 38% (n528) of participants and was associated with more severe disease (p5.005), higher colonization with SA (brachial right cease p5.01, popliteal right cease, p5.04, left popliteal cease, p5 .02) and had relation with allergy in the subgroup of atopic patients. CONCLUSIONS: Our study further emphasizes the role of the FLG gene polymorphism p.Pro478Ser, on AD pathogenesis and the IgE response in allergic adult subjects.
845
Clinical Features of Patients with Filaggrin Gene Mutations in Childhood Atopic Dermatitis Ryuhei Yasuoka, MD1, Tatsuki Fukuie, MD, PhD1, Jun-ichi Sakabe, PhD2, Yoshiki Tokura, MD, PhD2, Tomohide Taguchi, MD1; 1 Department of Pediatrics, Hamamatsu University School of Medicine, Shizuoka, Japan, 2Department of Dermatology, Hamamatsu University School of Medicine, Shizuoka, Japan. RATIONALE: Filaggrin (FLG) gene mutation carriers have increased risk of atopic dermatitis (AD). Herein we describe the clinical features of Japanese children with AD with and without FLG-null mutations. METHODS: Children with moderate-to-severe AD whose parents consented to filaggrin gene mutation analysis during February 2009 to July 2014 were enrolled. Each child was genotyped for the eight most prevalent FLG-null mutations in the Japanese population (R501X, 3321delA, S1695X, S1701X, S2554X, S2889X, S3296X, and K4022X). We retrospectively investigated total IgE, specific IgE (house dust mite, cedar pollen, egg white, milk, and wheat), eosinophil count, serum TARC, SCORAD, and eczema onset age on first examination. RESULTS: Of the 95 children (2 months–13 years, median 11 months), 25 had FLG-null mutations (positive ratio 35.7%, 22 heterozygotes, three compound heterozygotes). Eczema onset age was earlier in children with FLG-null mutations than in wild type. In children >1 year old at initial examination, the egg, milk, and wheat-specific IgEs in patients with FLG-null mutation were significantly higher than in wild type (P50.004, P 5 0.044, P 5 0.040, Mann–Whitney U test). Among only the cases with FLG-null mutations, egg white, house dust mite, and pollen-specific IgEs at 2 years were significantly lower in the AD patients treated before 1 year of age, compared with those who had been treated between 1 and 2 years (P50.059, P50.015, P50.014,Mann–Whitney U test). CONCLUSIONS: Our study indicates that eczema onset was earlier in children with FLG-null mutations and specific IgEs were higher on delayed treatment. Even with FLG-null mutation, sensitization to allergens might be preventable by treating AD early.
846
TUESDAY
Duration of Breastfeeding Modulates the Effect of Filaggrin Variants on the Risk of Eczema Early in Life: Results from the Isle of Wight Birth Cohort Ali H. Ziyab, PhD1, Wilfried Karmaus, MD, DrMed, MPH2, Hongmei Zhang, PhD2, John W. Holloway, PhD3, Susan L. Ewart, DVM, PhD4, Syed H. Arshad, DM, FRCP5,6; 1Kuwait University, Kuwait, 2University of Memphis, Memphis, TN, 3University of Southampton, Southampton, United Kingdom, 4Michigan State University, East Lansing, MI, 5The David Hide Asthma and Allergy Research Centre, United Kingdom, 6University of Southampton, United Kingdom. RATIONALE: Filaggrin gene (FLG) variants are common risk factors for eczema development; whereas, breastfeeding has been suggested as a possible protective factor. We hypothesized that breastfeeding will be protective in those with FLG variants. Thus, with increasing duration of breastfeeding the risk of eczema early in life will become similar among those with and without FLG variants. METHODS: In the Isle of Wight birth cohort (n 5 1,456), information regarding eczema was collected at ages 1, 2, 4, 10, and 18 years. Information on duration of breastfeeding was obtained at 1 and/or 2 years follow-ups. FLG variants (R501X, 2282del4, and S3247X) were genotyped in 1,150 participants. Using log-binomial regression models, the interaction effect between FLG variants and duration of breastfeeding on the risk of eczema at 1 and 2 years was evaluated controlling for potential confounders. RESULTS: FLG variants increased the risk of eczema by 1.64-fold (Pvalue 5 0.009) during the first 2-years of life. Duration of breastfeeding did not show an independent association with eczema. However, a possible interaction effect was observed (RRInteraction 5 0.97, PInteraction 5 0.062). The effect of FLG variants on the risk of eczema decreased as the duration of breastfeeding increased (in the absence of breastfeeding: RR52.27, P-
J ALLERGY CLIN IMMUNOL FEBRUARY 2015
value 5 0.002; at 6-months of breastfeeding: RR 5 1.27, P-value 5 0.323). CONCLUSIONS: Duration of Breastfeeding attenuated the association between FLG variants and eczema in early life. The mechanism through which this effect modification works needs to be investigated.
847
Filaggrin Gene Polymorphism Pro478Ser, but Not Loss-ofFunction Mutations Mp.Arg501Ter or C.2282del4, Relates with Atopic Dermatitis Severity and Increased Staphylococcal aureus Colonization in Adult Patients Liliana Rocha1, Cristina Lopes, MD2,3, Susana Fernandes4, Oksana Sokhatska5, Jose Soares6, Freni Tavaria7, Manuela Pintado7, Andre M. Moreira, MD8,9, Luis Delgado, MD8,10; 1Genetics Departament, Faculty of Medicine, University of Porto, Portugal, Porto, Portugal, 2Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Portugal, Porto, Portugal, 3Allergy Unit, Pedro Hispano Hospital, Matosinhos, Portugal, 4Genetics Department Medical faculty Porto University, 5Immunology Laboratory, Medical Faculty, Porto University, 6Biology and Fine Chemistry Unit, Biotechnology Faculty, Catholic University, Porto, Portugal, 7Biology and Fine Chemistry Unit, Biotechnology Faculty, Catholic University, Portugal, 8Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Porto, Portugal, 9Allergy and Clinical Immunology Department, Centro Hospitalar S~ao Jo~ao, EPE, Porto, Portugal, 10 Immunology Lab, Department of Clinical Pathology, Porto, Portugal. RATIONALE: We aimed to assess the impact of filaggrin (FLG) gene mutations p.Arg501Ter, c.2282del4 and polymorphism p.Pro478Ser on disease severity, skin bacterial colonization, and allergy in Portuguese subjects with long term atopic dermatitis (AD). METHODS: In this cross sectional study, data from 73 patients, (30613 years, 61% female, 77% atopic) with AD for 16610 years was analyzed. Mutations were analyzed by PCR amplification of exon 3 of FLG gene and Sanger sequencing, disease severity trough SCORAD, allergy by serum levels of IgE, Phadiatop, eosinophil cationic protein and specific IgE to Staphylococcus aureus (SA) enterotoxin A, B, C , TSST and Malassezia spp. Number of colony forming units of staphylococci and SA species in 25 cm2 of poplitea, brachial ceases, interscapular regions were determined. Non-parametric statistic analyses and chi-square were used. RESULTS: FLG mutations p.Arg501Ter (n59) and c.2282del4 (n52) were identified in 14.8% patients and were not associated with AD severity, allergic or microbiological parameters; p.Pro478Ser polymorphism was present in 38% (n528) of participants and was associated with more severe disease (p5.005), higher colonization with SA (brachial right cease p5.01, popliteal right cease, p5.04, left popliteal cease, p5 .02) and had relation with allergy in the subgroup of atopic patients. CONCLUSIONS: Our study further emphasizes the role of the FLG gene polymorphism p.Pro478Ser, on AD pathogenesis and the IgE response in allergic adult subjects.