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Tuesday, August 31, 2010

Spectroscopy mirrors AD genotypes

Mutations in the filaggrin gene family are known to be associated with atopic dermatitis (AD). Filaggrin (FLG) is a critical component of the epidermal differentiation complex and its degradation products accumulate in the stratum corneum (SC) layer with hygroscopic amino acids to produce natural moisturizing factor (NMF), which is lost via transepidermal water depletion in AD patients. In this issue, O’Regan and co-authors propose that the filaggrin-associated AD genotype could be detected by Raman spectroscopy of the NMF content of the SC and that the NMF content could serve to separate FLG-associated AD from non-FLG-associated AD. Further, they examine the correlation of FLG-associated AD to transepidermal water loss (TEWL) and palmar hyperlinearity.

O’Regan and colleagues generate depth profiles of NMF content from AD study subjects and compare the profiles to Raman spectra for normal SC. Reference spectra profiles include tyrosine, which is known to be elevated in FLG-associated AD. They find that NMF content spectra can distinguish not only FLG-associated AD from non-FLG-associated AD, but also minor allele heterozygosity. Additionally, tyrosine content is significantly associated with the homozygous FLG genotype, suggesting a possible clinical biomarker. O’Regan et al. also report significant relationship between the clinical finding of palmar hyperlinearity, NMF content and filaggrin genotype.

Finally, the authors find that TEWL in moderate to severe AD is independent of filaggrin genotype, suggesting that TEWL results from other AD immunopathology.

Do you have any questions for the authors, or comments about this study? We want to hear from you. Please feel free to post your own questions or comments. All questions and comments will be forwarded to the authors for a response.

1 comment:

  1. We asked senior author Dr. Alan Irvine to tell us a little more about this report:

    JACI: Given that TEWL is independent of genotype, what clinical benefit might be associated with the ability to distinguish FLG-associated AD from non-FLG-associated AD?

    Irvine: On the basis of our work, grossly elevated TEWL looks like an common end point in moderate-to-severe atopic dermatitis rather than having a specific genetic basis, thus many pathomechanisims lead to this barrier failure. When AD is well established the skin barrier is severely deranged, but to focus on the end stage damage may be to miss a therapeutic opportunity. Knowing FLG genotypes within would be of great value in determining patient-specific therapeutic approaches if FLG status was known to influence response to specific therapeutic interventions or to favour interventions at specific time points in the disease trajectory. Determining these genotype specific responses should be the focus of ongoing clinical and basis research.