Interaction Between the R501X Filaggrin Mutation and Disease Severity Associates with Increased Staphylococcus Aureus Colonization in European American Subjects with Atopic Dermatitis
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Nicholas M Rafaels, Alexandre Lockhart, Denise C. Babineau, PhD, Keli Artis, BS, Gloria L. David, PhD, Takeshi Yoshida, PhD, Mark Boguniewicz, MD FAAAAI, Peck Y. Ong, MD FAAAAI, Anna De Benedetto, MD FAAAAI, Jon M. Hanifin, MD FAAAAI, Eric L Simpson, MD, MCR, Amy S Paller, Emma Guttman-Yassky, MD PhD, Lynda C. Schneider, MD FAAAAI, Rasika A. Mathias, ScD, Kathleen C Barnes, PHD, Donald Y. Leung, MD PhD FAAAAI, Lisa A. Beck, MD FAAAAI
Rationale: Filaggrin (FLG) mutations are strongly linked to Atopic Dermatitis (AD) and AD severity. FLG mutations may also be predisposed to S. aureus colonization because of reduced FLG end products with anti-staphylococcal properties. We propose FLG mutations as risk factors for staph phenotypes in AD subjects.

Methods: Four common FLG null mutations (2282del4, R501X, R2447X, S3247X) were genotyped in 423 S. aureus colonized (ADStaph+) and 544 S.aureus non-colonized (ADStaph-) European American (EA) AD subjects. ADStaph+ grew S. aureus from skin swabs obtained at lesional or non-lesional sites; ADStaph- had no growth. Disease severity was assessed by Eczema Area and Severity Index (EASI). Contribution of FLG mutations to S. aureus colonization in mild, moderate and severe AD was assessed by including interaction between EASI and FLG mutations in logistic regression models adjusting for total IgE, age, and sex. Similar analyses were performed for staph culture scoring (1-4).

Results: The R501X effect (minor allele frequency [MAF]=12.7%) on S. aureus colonization was modified by EASI (P=0.002). In subjects with severe and mild AD, odds of S. aureus colonization were 2.09 fold higher and 0.36 fold lower, respectively, in carriers than noncarriers for R501X. Culture score was also modified by EASI for R501X carriers versus noncarriers (severe OR=1.47; mild OR=0.59; P=0.015).  No association was observed between 2282del4, R2447X, or S3247X (MAF:14.8%, 2.6%, 2.1%; respectively) and S. aureus colonization.

Conclusions: Evidence suggests R501X mutation affects susceptibility to S. aureus colonization in EA AD patients but this effect is lost in milder disease. Analyses are underway in ethnically diverse populations.