Plucked hair follicles from patients with chronic discoid lupus erythematosus show a disease-specific molecular signature

Abstract

ObjectiveWhen faced with clinical symptoms of scarring alopecia—the standard diagnostic pathway involves a scalp biopsy which is an invasive and expensive procedure. This project aimed to assess if plucked hair follicles (HFs) containing living epithelial cells can offer a non-invasive approach to diagnosing inflammatory scalp lesions.MethodsLesional and non-lesional HFs were extracted from the scalp of patients with chronic discoid lupus erythematosus (CDLE), psoriasis and healthy controls. RNA was isolated from plucked anagen HFs and microarray, as well as quantitative real-time PCR was performed.ResultsHere, we report that gene expression analysis of only a small number of HF plucked from lesional areas of the scalp is sufficient to differentiate CDLE from psoriasis lesions or healthy HF. The expression profile from CDLE HFs coincides with published profiles of CDLE from skin biopsy. Genes that were highly expressed in lesional CDLE corresponded to well-known histopathological diagnostic features of CDLE and included those related to apoptotic cell death, the interferon signature, complement components and CD8+ T-cell immune responses.ConclusionsWe therefore propose that information obtained from this non-invasive approach are sufficient to diagnose scalp lupus erythematosus. Once validated in routine clinical settings and compared with other scarring alopecias, this rapid and non-invasive approach will have great potential for paving the way for future diagnosis of inflammatory scalp lesions.

RNA tape sampling in cutaneous lupus erythematosus discriminates affected from unaffected and healthy volunteer skin

“…Our finding that IFN pathway genes recovered by tape harvesting distinguish between CLE-A and CLE-U or HV skin is supported in the CLE transcriptomics literature. [44][45][46][47][48][49][50] Many of the IFN response genes with highest ranking fold changes in previous studies are also differentially regulated in this tape-derived RNA study. These include IFI27, IFI44L, IFI44, OAS1 (blood from participants with CLE), 44 CCL5, CXCL9, Mx1, OAS2 and AIM2 (affected skin biopsies from participants with CLE) 45 46 50 and Mx1, IFI6, OAS2, XAF1, CXCL10 and IFI27 (follicular epithelium from participants with CLE).…”

“…These include IFI27, IFI44L, IFI44, OAS1 (blood from participants with CLE), 44 CCL5, CXCL9, Mx1, OAS2 and AIM2 (affected skin biopsies from participants with CLE) 45 46 50 and Mx1, IFI6, OAS2, XAF1, CXCL10 and IFI27 (follicular epithelium from participants with CLE). 47 Previous evidence also underpins an important role for cytotoxic NK cell-mediated and T cell-mediated apoptosis in CLE pathogenesis. 19 45 51 In support of this hypothesis, in CLE transcript profiling studies comparing CLE lesions with unaffected skin or with HV skin using full-thickness skin biopsy 45 or follicular epithelium from plucked hairs, 47 upregulated IFN response genes included the apoptosis-related XAF1, OAS1 and OAS2, consistent with our findings.…”

“…47 Previous evidence also underpins an important role for cytotoxic NK cell-mediated and T cell-mediated apoptosis in CLE pathogenesis. 19 45 51 In support of this hypothesis, in CLE transcript profiling studies comparing CLE lesions with unaffected skin or with HV skin using full-thickness skin biopsy 45 or follicular epithelium from plucked hairs, 47 upregulated IFN response genes included the apoptosis-related XAF1, OAS1 and OAS2, consistent with our findings. Also convergent with our findings, in previous CLE transcriptome studies, genes expressed in cytotoxic NK and T cells were upregulated, including FAS, GZMB, PRF1 and GNLY.…”

“…These include IFI27, IFI44L, IFI44, OAS1 (blood from participants with CLE), 44 CCL5, CXCL9, Mx1, OAS2 and AIM2 (affected skin biopsies from participants with CLE) 45 46 50 and Mx1, IFI6, OAS2, XAF1, CXCL10 and IFI27 (follicular epithelium from participants with CLE). 47 …”

Non-invasive Approaches for the Diagnosis of Autoimmune/Autoinflammatory Skin Diseases—A Focus on Psoriasis and Lupus erythematosus

“…Since the hair follicle is the main target in CDLE, we used 3–5 plucked anagen hair follicles as a non-invasive diagnostic approach (134). We found increased expression of ISGs that are known to play important role in the pathogenesis of the disease (121).…”