Gene Expression Different in Allergic, Irritant Contact Dermatitis

By Reuters Staff

January 04, 2021

NEW YORK (Reuters Health) - Artificial intelligence (AI) can help identify biomarkers to distinguish between contact dermatitis (CD) due to allergic reactions or to irritants, according to new findings.

There were major differences in gene expression between the two CD types, Dr. Nanna Fyhrquist of Karolinska Institutet in Stockholm and colleagues found.

"The identified biomarkers represent key features of skin inflammation and repair, which might - in addition to serving as biomarkers for diagnostic purposes - prove to be efficient indicators of disease risk or improvement," they write in the Proceedings of the National Academy of Sciences.

CD accounts for more than 90% of occupational skin disorders, and includes allergic CD (ACD) and irritant contact dermatitis (ICD), the authors explain. ACD involves hypersensitivity to sensitizing agents, while ICD results from skin damage caused by irritants.

The two entities are difficult to distinguish from one another clinically. "Although patch testing is the current gold standard for ACD diagnosis, subjective clinical interpretation cannot be straightforward and standardized; thus, this approach is prone to errors leading to repeated and additional tests," Dr. Fyhrquist and her colleagues write.

The researchers used transcriptome analysis and machine learning to look for distinct genetic signatures of ACD and ICD in 89 biopsies of positive patch tests against four contact allergens and two irritants. They validated potential biomarkers discovered with coexpression network analysis and Random Forest classification in an independent group of patients.

The four contact sensitizers had 641 differentially expressed genes (DEGs) in common, while the two irritants had 339 DEGs in common. All six exposures were associated with 152 shared DEGs.

In ACD, immune signaling was upregulated compared to ICD, while cornification, keratinization and cell division were downregulated. More severe CD reactions were associated with a greater number of dysregulated genes.

T cell signaling occurs in both ACD and ICD, the authors note, so T cell infiltration is not a good way to tell the difference between them.

"Instead, the presence of innate immune cells, such as macrophages and NK cells, and related signaling makes the difference and is apparently the result of antigen-specific T cell-driven signaling and cross-talk between the two arms of immunity, resulting in the amplification of the response in ACD," they write.

"We tested these biomarker sets in an independent patient group suffering from CD and demonstrate their potential applicability in reactions induced by agents different from those that were used for biomarker discovery. Thus, we provide high-potential molecular biomarker candidates for further clinical evaluation," the authors conclude.

Dr. Fyhrquist was not available for an interview by press time.

SOURCE: https://bit.ly/3h81zJe PNAS, online December 14, 2020.

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