Atopic dermatitis in African American patients is TH2/TH22-skewed with TH1/TH17 attenuation

Abstract

The molecular phenotype of AA AD skin is characterized by attenuated Th1 and Th17 but similar Th2/Th22-skewing to EA AD. Our data encourages a personalized medicine approach accounting for phenotype-specific characteristics in future development of targeted therapeutics and clinical trial design for AD.

Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial

“…[1][2][3]11,14,38 Although AD has been long recognized as a T H 2-driven disease, recently, it has been shown to have a significant T H 22 component, 1,29,33,[55][56][57][58][59] with several clinical and molecular disease subtypes that show variable contributions of T H 1 and T H 17 and differential T H 2/ T H 22 activation. 30,32,33,[59][60][61][62][63][64][65][66][67][68][69] Crisaborole topical treatment induced significant modulation of several immune and KC pathways beyond those related to T H 2 inflammation, suggesting that this topical treatment might be broadly applicable across the AD phenotype spectrum. This notion is supported by the highly significant effects of crisaborole on measures of epidermal hyperplasia, including the IL-17/IL-22-induced S100As, which are dysregulated in all AD phenotypes.…”

“…This notion is supported by the highly significant effects of crisaborole on measures of epidermal hyperplasia, including the IL-17/IL-22-induced S100As, which are dysregulated in all AD phenotypes. 3,30,32,33,63,68,70 Future studies in specific patient populations should evaluate whether there are any differences in therapeutic response.…”

“…TaqMan Low Density Array cards were used for qRT-PCR, as previously reported. 32,33 Eukaryotic 18S rRNA was used as an endogenous control. Expression values (threshold cycle [Ct]) were normalized to Rplp0.…”

Genetic ancestry does not explain increased atopic dermatitis susceptibility or worse disease control among African American subjects in 2 large US cohorts

“…A recent study that sought to characterize the global molecular profile of patients with AD found significant variation in cellular infiltrates, as well as expression of immune and barrier genes between African American and white subjects. 39 The extent to which such changes are due to environmental and behavioral factors should be explored in future work. The fact that the skin pigment PRS did not correlate with AD risk in the GERA cohort provides evidence that AD is likely independent of skin pigment per se and that the pigment difference between African American and white subjects does not explain the AD prevalence difference.…”

Increased cardiovascular and atherosclerosis markers in blood of older patients with atopic dermatitis

“…Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, driven by T H 2/T H 22, with variable degrees of T H 1/T H 17 involvement in different subtypes. [1][2][3] Although most cases begin in early childhood, persistence into adulthood is common, suggesting that AD may be a life-long disease. 4,5 AD is a heterogeneous disease with various recognized endotypes based on IgE status, filaggrin mutations, and, more recently, ethnic and age-related variations.…”