To learn more about inflammatory skin conditions, researchers isolated immune cells, focusing primarily on T cells, from the skin of 31 volunteers. They then sequenced the RNA of each cell to provide a tell-tale portrait of its genomic features. This ‘single-cell analysis’ allowed them to capture high-resolution portraits of 41 different immune cell types found in individual skin samples.
The National Institutes of Health-funded team was led by Drs Jeffrey Cheng and Raymond Cho, of the University of California.
The team produced molecular signatures of the immune cells. The researchers then compared the signatures from the hard-to-diagnose rashes to those of confirmed cases of atopic dermatitis and psoriasis. They wanted to see if the signatures could help to reach clearer diagnoses. The signatures revealed common immunological features as well as underlying differences. Importantly, the researchers found that the signatures allowed them to move forward and classify the indeterminate rashes.
Already, the work has identified molecules that help to define major classes of human inflammatory skin diseases. The team has developed a website called RashX, to help classify rashes in many other cases where the diagnosis is otherwise uncertain.
It is enabling practicing dermatologists and researchers around the world to submit their single-cell RNA data from their difficult cases. Such analyses are now being done at a small, but growing, number of academic medical centres.
The RashX site (https://rashx.ucsf.edu) is a free computational tool enabling scientists and doctors to learn more about their patients with specific cases of unusual, long-lasting rashes not fitting common categories (such as atopic dermatitis and psoriasis vulgaris). The website allows users to receive an emailed, comparative visualisation of uploaded sample in context of atopic dermatitis and psoriasis vulgaris reference samples.
RashX is not a profiling clinical test. It is an experimental approach being trialled. There is no insurance funding or reimbursement for such molecular tests currently. The data required for RashX is single-cell RNA sequencing derived from a fresh skin biopsy. Currently, there are a very limited but growing number of academic centres performing such profiling on a research basis. If you are a clinician and want to alert us to such a case, please email us at rashx@ucsf.edu, but do not include any patient-identifying details.
RashX is currently based on 10X Genomics Chromium of T cells obtained from skin biopsies. This means that an academic centre requires the expertise and funding (as insurance does not pay for research-oriented tests) to take a sample from a patient, profile it using Chromium technology, analyse the resulting complex genetic data, and enter it into RashX. The researchers are currently extending RashX to additional molecular profiling platforms.
REFERENCES:
NIH Director’s Blog. A More Precise Way to Knock Out Skin Rashes. https://directorsblog.nih.gov/2022/04/26/a-more-precise-way-to-knock-out-skin-rashes/
RashX: https://rashx.ucsf.eduearn 1 general CPD point.
