Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis

Garelli, Colton J.; Refat, Maggi Ahmed; Nanaware, Padma P.; Ramirez-Ortiz, Zaida G.; Rashighi, Mehdi; Richmond, Julius B.

doi:10.3389/fimmu.2020.01353

Cited by 39 publications

(47 citation statements)

References 183 publications

(182 reference statements)

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“…Using novel analyses, we found that DLE lesions harbor a unique immunoglobulin signature and an enrichment of skin B cells compared to ACLE or SCLE lesions. Intriguingly, this B cell signature was highest in patients with CLE without concomitant SLE, including within the entire cohort of DLE patients (2). Our results demonstrate that a B cell gene signature in the skin distinguishes DLE from ACLE and SCLE and that increased B cells in the skin of DLE patients is indicative of a lower rate of accompanying systemic disease.…”

Section: Introductionmentioning

confidence: 55%

“…SLE involves multiple organ systems, including the skin, where the distinct type of inflammation is termed cutaneous lupus erythematosus (CLE). CLE can occur in isolation or as a skin manifestation associated with underlying systemic lupus erythematosus (SLE) (2). CLE is relatively understudied compared to SLE, which contributes to a lack of understanding of disease heterogeneity in CLE pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, basic transcriptional comparisons have not identified robust distinguishing molecular signatures between subtypes (13,14). Further, DLE is more likely to occur without underlying SLE compared to ACLE or SCLE (2,15), yet it is not clear if the presence or absence of systemic disease is related to the differences observed in cutaneous manifestations of lupus (16).…”

Section: Introductionmentioning

confidence: 99%

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B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the Presence of Systemic Disease Activity

et al. 2021

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Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.

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Section: Introductionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the Presence of Systemic Disease Activity

et al. 2021

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“…Cutaneous lupus erythematosus (CLE) is a spectrum of autoimmune skin diseases encompassing several clinical subtypes, all of which are characterized by interface dermatitis, or inflammation at the dermal-epidermal junction ( 58 ). The most well-known manifestation of CLE is the characteristic erythematous malar rash, which is associated with systemic lupus erythematosus (SLE).…”

Section: Trm In Cutaneous Lupus Erythematosusmentioning

confidence: 99%

Resident Memory T Cells in Autoimmune Skin Diseases

2021

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Tissue resident memory T cells (TRM) are a critical component of the immune system, providing the body with an immediate and highly specific response against pathogens re-infecting peripheral tissues. More recently, however, it has been demonstrated that TRM cells also form during autoimmunity. TRM mediated autoimmune diseases are particularly destructive, because unlike foreign antigens, the self-antigens are never cleared, continuously activating self-reactive TRM T cells. In this article, we will focus on how TRMs mediate disease in autoimmune skin conditions, specifically vitiligo, psoriasis, cutaneous lupus erythematosus, alopecia areata and frontal fibrosing alopecia.

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“…1 Subtypes of cutaneous lupus erythematosus (CLE) contained acute CLE, subacute CLE, intermittent CLE and chronic CLE, divided based on chronicity, morphology together with the distribution of skin lesions. 2 Among different subtypes of CLE, discoid lupus erythematosus (DLE) is the most common chronic type. 3 Its skin symptoms include erythematosus, atrophic scarring, dyspigmentation, follicular hyperkeratosis and even alopecia.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic analysis of key biomarkers and immune filtration of skin biopsy in discoid lupus erythematosus

Xiang

Chen

Yang

et al. 2021

Lupus

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Objective Discoid lupus erythematosus (DLE) is the most common category of chronic cutaneous lupus erythematosus, where the pathological process is proved to be closely associated with immunity. This bioinformatic analysis sought to identify key biomarkers and to perform immune infiltration analysis in the skin biopsy samples of DLE. Methods GSE120809, GSE100093, GSE72535, GSE81071 were used as the data source of gene expression profiles, altogether containing 79 DLE samples and 47 normal controls (NC). Limma package was applied to identify differentially expressed genes (DEGs) and additional Gene Ontology (GO) together with The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were done. Protein-protein interaction network (PPI) was constructed using STRING and Cytoscape. Hub genes were selected by CytoHubba. Finally, immune filtration analysis was finished by the CIBERSORT algorithm, and comparisons between the two groups were accomplished. Results A total of 391 DEGs were identified, which were composed of 57 up-regulated genes and 334 down-regulated genes. GO and KEGG enrichment analyses revealed that DEGs were closely related with different steps in the immune response. Top 10 hub genes included GBP2, HLA-F, IFIT2, RSAD2, ISG15, IFIT1, IFIT3, MX1, XAF1 and IFI6. Immune filtration analysis from CIBERSORT had found that compared with NC, DLE samples had higher percentages of CD8+ T cells, T cells CD4 memory activated, T cells gamma delta, macrophages M1 and lower percentages of T cells regulatory, macrophages M2, dendritic cells resting, mast cells resting, mast cells activated. Conclusion This bioinformatic study selected key biomarkers from the contrast between DLE and NC skin samples and is the first research to analyze immune cell filtration in DLE.

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Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis

Cited by 39 publications

References 183 publications

B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the Presence of Systemic Disease Activity

B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the Presence of Systemic Disease Activity

Resident Memory T Cells in Autoimmune Skin Diseases

Bioinformatic analysis of key biomarkers and immune filtration of skin biopsy in discoid lupus erythematosus

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