Gene Expression Profiling in the Skin Reveals Strong Similarities between Subacute and Chronic Cutaneous Lupus that Are Distinct from Lupus Nephritis

Ko, Wei-Che; Li, Li; Young, Taylor; McLean-Mandell, Riley; Deng, April; Vanguri, Vijay K.; Dresser, Karen; Harris, John E.

doi:10.1016/j.jid.2021.04.030

Cited by 23 publications

(18 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All four dog cases from our study presented with CLE-like features in addition to other non-specific clinical signs, after which hierarchical gene expression clustering together with consultation from a veterinary pathologist and dermatologist helped clarify the diagnoses. Consistent with other published papers ( 23 , 37 , 38 ), our gene expression analysis of these four complex cases revealed high expression of IFNG and CXCL10 , which are important biomarkers in CLE pathogenesis ( 39 ). Pro-inflammatory cytokines IL12 and TNF were highly expressed in CLE, supporting the role of these genes in mediating lupus pathogenesis ( 40 ).…”

Section: Discussionsupporting

confidence: 91%

“…However, clinicians and physicianscientists still face a considerable challenge in correctly diagnosing and treating autoimmune diseases, including CLE (32). There is growing knowledge about the enormous opportunities that gene expression analysis provides for personalized medicine (33) and the efficiency of machine learning gene expression analysis in diagnosing autoimmune diseases (34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Using Gene Expression Analysis to Understand Complex Autoimmune Skin Disease Patients: A Series of Four Canine Cutaneous Lupus Erythematosus Cases

et al. 2022

View full text Add to dashboard Cite

Cutaneous Lupus Erythematosus (CLE) is an autoimmune skin disease that occurs in almost two-thirds of people with Systemic Lupus Erythematosus (SLE) and can exist as its own entity. Despite its negative impact on the quality of life of patients, lupus pathogenesis is not fully understood. In recent years, the role of gene expression analysis has become important in understanding cellular functions and disease causation within and across species. Interestingly, dogs also develop CLE, providing a spontaneous animal model of disease. Here, we present a targeted transcriptomic analysis of skin biopsies from a case series of four dogs with complex autoimmunity with suspected CLE. We identified 92 differentially expressed genes (DEGs), including type 1 interferon, B cell, and T cell-related genes, in the four cases compared to healthy skin margin controls. Additionally, we compared our results with existing CLE datasets from humans and mice and found that humans and canines share 49 DEGs, whereas humans and mice shared only 25 DEGs in our gene set. Immunohistochemistry of IFNG and CXCL10, two of the most highly upregulated inflammatory mediators, confirmed protein-level expression and revealed immune cells as the primary source of CXCL10 in dogs with SLE, whereas keratinocytes stained strongly for CXCL10 in dogs without SLE. We propose that gene expression analysis may aid the diagnosis of complex autoimmune skin diseases and that dogs may provide important insights into CLE and SLE pathogeneses, or more broadly, skin manifestations during systemic autoimmunity.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Using Gene Expression Analysis to Understand Complex Autoimmune Skin Disease Patients: A Series of Four Canine Cutaneous Lupus Erythematosus Cases

et al. 2022

View full text Add to dashboard Cite

show abstract

“…While there are consistently observed cellular and molecular features in patients with CLE and/or SLE, such as a type I interferon (IFN) gene signature in the blood and skin (6)(7)(8)(9)(10) and peripheral B cell dysfunction (11,12), the shared and unique molecular and cellular features of ACLE, SCLE, and CCLE remain poorly understood. 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%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

“…Recent work by Kingsmore et al ( 71 ) noted increased apoptotic mitochondrial gene signatures in DLE and lupus nephritis, suggesting a role for the intrinsic apoptotic pathway, and positive correlation with inflammatory cell signatures supports the intrinsic link of apoptosis with inflammation. Gene set expression analysis with microarray and RNA-sequencing of CLE skin and blood identified other genes, such as GZMB , BAX , and various caspases ( CASP8 / 10 ) among others ( 1 , 64 , 72 – 75 ). Differential expression analysis of CLE lesional skin and blood skewed toward lesional skin, though apoptosis signatures were noted in both environments.…”

Section: Resultsmentioning

confidence: 99%

The Genetic Landscape of Cutaneous Lupus Erythematosus

2022

View full text Add to dashboard Cite

Cutaneous lupus erythematosus (CLE) is an autoimmune connective tissue disease that can exist as a disease entity or within the context of systemic lupus erythematosus (SLE). Over the years, efforts to elucidate the genetic underpinnings of CLE and SLE have yielded a wealth of information. This review examines prior studies investigating the genetics of CLE at the DNA and RNA level and identifies future research areas. In this literature review, we examined the English language literature captured within the MEDLINE and Embase databases using pre-defined search terms. First, we surveyed studies investigating various DNA studies of CLE. We identified three predominant areas of focus in HLA profiling, complement deficiencies, and genetic polymorphisms. An increased frequency of HLA-B8 has been strongly linked to CLE. In addition, multiple genes responsible for mediating innate immune response, cell growth, apoptosis, and interferon response confer a higher risk of developing CLE, specifically TREX1 and SAMHD1. There was a strong association between C2 complement deficiency and CLE. Second, we reviewed literature studying aberrations in the transcriptomes of patients with CLE. We reviewed genetic aberrations initiated by environmental insults, and we examined the interplay of dysregulated inflammatory, apoptotic, and fibrotic pathways in the context of the pathomechanism of CLE. These current learnings will serve as the foundation for further advances in integrating personalized medicine into the care of patients with CLE.

show abstract

Gene Expression Profiling in the Skin Reveals Strong Similarities between Subacute and Chronic Cutaneous Lupus that Are Distinct from Lupus Nephritis

Cited by 23 publications

References 52 publications

Using Gene Expression Analysis to Understand Complex Autoimmune Skin Disease Patients: A Series of Four Canine Cutaneous Lupus Erythematosus Cases

Using Gene Expression Analysis to Understand Complex Autoimmune Skin Disease Patients: A Series of Four Canine Cutaneous Lupus Erythematosus Cases

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

The Genetic Landscape of Cutaneous Lupus Erythematosus

Contact Info

Product

Resources

About