Αρχειοθήκη ιστολογίου

Σάββατο 15 Σεπτεμβρίου 2018

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

Publication date: Available online 14 September 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Riana D. Sanyal, Ana B. Pavel, Jacob Glickman, Tom C. Chan, Xiuzhong Zheng, Ning Zhang, Inna Cueto, Xiangyu Peng, Yeriel Estrada, Judilyn Fuentes-Duculan, Andrew F. Alexis, James G. Krueger, Emma Guttman-Yassky

Abstract
Background

African Americans/(AA) are disproportionately impacted by atopic dermatitis/(AD) with increased prevalence and therapeutic challenges unique to this population. Molecular profiling data informing development of targeted therapeutics for AD are derived primarily from European American/(EA) patients. These studies are absent in AA, hindering development of effective treatments for this population.

Objective

We sought to characterize the global molecular profile of AD in skin of AA patients as compared with that of EA AD and healthy controls.

Methods

We performed RNA-Seq with RT-PCR validation and immunohistochemistry studies in lesional and non-lesional skin of AA and EA AD patients versus healthy controls.

Results

AA AD lesions were characterized by greater infiltration of dendritic cells/(DCs) marked by the high-affinity IgE receptor/(FcεR1+) compared with EA AD (p<0.05). Both AD cohorts showed similarly robust upregulation of Th2-related (CCL17/18/26) and Th22-related markers (IL- 22, S100A8/9/12), but AA AD featured decreased expression of innate immune (TNF, IL-1β), Th1-related (IFN-γ, MX1, IL-12RB1), and Th17-related markers (IL-23p19, IL-36G, CXCL1) versus EA AD (p<0.05). Th2 (IL-13) and Th22-related products (IL-22, S100A8/9/12) and serum IgE were significantly correlated with clinical severity (SCORAD) in AA. Fillagrin (FLG) was exclusively downregulated in EA AD, while loricrin (LOR) was downregulated in both AD cohorts and negatively correlated with SCORAD in AA.

Conclusion

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 phenotypespecific characteristics in future development of targeted therapeutics and clinical trial design for AD.



https://ift.tt/2NRuaGV

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου