Assessment of Treatment-Relevant Immune Biomarkers in Psoriasis and Atopic Dermatitis: Toward Personalized Medicine in Dermatology

Abstract

Immunologically targeted therapies have revolutionized the treatment of inflammatory dermatoses, including atopic dermatitis and psoriasis. Although immunologic biomarkers hold great promise for personalized classification of skin disease and tailored therapy selection, there are no approved or widely used approaches for this in dermatology. This review summarizes the translational immunologic approaches to measuring treatment-relevant biomarkers in inflammatory skin conditions. Tape strip profiling, microneedle-based biomarker patches, molecular profiling from epidermal curettage, RNA in situ hybridization tissue staining, and single-cell RNA sequencing have been described. We discuss the advantages and limitations of each and open questions for the future of personalized medicine in inflammatory skin disease.

Figure 1.. RNA- and protein-based biomarkers for biologic therapy selection and diagnosis.

Various methods exist for collecting biomarkers from the skin, including shave or punch biopsy or minimally invasive approaches such as tape stripping, superficial epidermal curettage, or microneedle patches. In addition, systemic biomarkers from the blood can be measured. RNA analysis techniques include RT-PCR, microarray, sequencing approaches, or in situ analysis using hybridization probes. Proteins can be analyzed by IHC/IF, immunoassay, MS-based methods, proximity extension, or aptamer-based methods for high-throughput proteomics. Each method of analysis is labeled with compatible collection methods on the basis of references in this review. The RNA or protein levels of different immunologic molecules or other molecular correlates could be used for rational selection of biologic therapy and to aid in the diagnosis of CIRs. CIR, clinically/histopathologically indeterminate rash; IF, immunofluorescence; IHC, immunohistochemistry; RISH, RNA in situ hybridization; scRNA-seq, single-cell RNA sequencing; MS, mass spectrometry.

Figure 2.. Skin sampling and processing for different investigational techniques for personalized therapy selection in inflammatory skin disease.

(a) For tape stripping, an applicator is applied to the skin for consecutive tape strips. RNA or proteins are extracted from the tape strips and quantified. (b) For the microneedle-based dermal biomarker patch (Mindera Health, San Diego, CA), a microneedle patch which has probes extending into the superficial dermis is applied to the skin. RNA is extracted, reverse transcribed, and sequenced. (c) For molecular profiling from epidermal curettage (Castle Biosciences, Friendswood, TX), the skin is scraped with a curette, and RNA is isolated from the skin sample and analyzed by RT-PCR. (d) For RISH, a skin biopsy is obtained. A probe complementary to the RNA molecule of interest is added to the tissue slide, and a chromogenic or fluorescent marker is added in the detection step. (e) For single-cell RNA sequencing, a biopsy is obtained, and the skin sample is dissociated into single cells. Single-cell cDNA library preparation is performed, and the cDNA library is sequenced using next-generation sequencing. FFPE, formalin-fixed, paraffin-embedded; RISH, RNA in situ hybridization.