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The Genetic Landscape of Cutaneous Lupus Erythematosus.

ABSTRACT: 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.

SUBMITTER: Chen HW

PROVIDER: S-EPMC9201079 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Immunogenetics of cutaneous lupus erythematosus.

Project description:Purpose of reviewSystemic lupus erythematosus (SLE) is the prototypic autoimmune condition, often affecting multiple organ systems, including the skin. Cutaneous lupus erythematosus (CLE) is distinct from SLE and may be skin limited or associated with systemic disease. Histopathologically, the hallmark of lupus-specific manifestations of SLE and CLE is an interface dermatitis. The cause of SLE and CLE is likely multifactorial and may include shared genetic factors. In this review, we will discuss the genetic findings related to the cutaneous manifestations of SLE and isolated CLE, with a particular focus on the lupus-specific CLE subtypes.Recent findingsSeveral major histocompatibility complex and nonmajor histocompatibility complex genetic polymorphisms have been identified which may contribute to the cutaneous manifestations of SLE and to CLE. Most of these genetic variants are associated with mechanisms attributed to the pathogenesis of SLE, including pathways involved in interferon and vitamin D regulation and ultraviolet light exposure. Although there is overlap between the genetic factors associated with SLE and CLE, there appear to be unique genetic factors specific for CLE.SummaryImproved understanding of the genetics of CLE may lead to the creation of targeted therapies, improving outcomes for patients with this challenging dermatologic condition.

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Emerging Therapies in Cutaneous Lupus Erythematosus

Project description:Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can occur with or without underlying systemic lupus erythematosus (SLE) and often has a profoundly negative impact on patient quality of life. There is substantial need for new and more effective therapies to treat CLE. CLE has a multifactorial pathogenesis that involves several key immune cells and pathways, including abnormalities in innate (e.g., type 1 interferon pathways) and adaptive immune responses (e.g., B and T cell autoreactivity), presenting multiple opportunities for more targeted therapies that do not require immunosuppression. Here we review several emerging therapies and their efficacy in CLE. Anifrolumab and belimumab have both been approved for the treatment of SLE in recent years, and clinical trial evidence suggests some forms of CLE may improve with these agents. Therapies currently in development that are being evaluated with CLE-specific outcome measures include BIIB059 and VIB7734, which target plasmacytoid dendritic cells (pDCs), and iberdomide, a cereblon modulator. These novel therapies all have previously demonstrated clinical benefit in some forms of CLE. Other therapies which target molecules believed to play a role in CLE pathogenesis, such as Janus kinases (JAKs), spleen tyrosine kinase (SYK), interferon γ (IFNγ), IL-12, and IL-23, have been evaluated in lupus clinical trials with skin-specific outcomes but failed to meet their primary endpoints.

| S-EPMC9313535 | biostudies-literature

Gene expression in cutaneous lupus erythematosus

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2017-02-24 | E-MTAB-5542 | biostudies-arrayexpress

Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis.

Project description:Cutaneous Lupus Erythematosus (CLE) is a clinically diverse group of autoimmune skin diseases with shared histological features of interface dermatitis and autoantibodies deposited at the dermal-epidermal junction. Various genetic and environmental triggers of CLE promote infiltration of T cells, B cells, neutrophils, antigen presenting cells, and NK cells into lesional skin. In this mini-review, we will discuss the clinical features of CLE, insights into CLE immunopathogenesis, and novel treatment approaches.

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Photoprotective habits of patients with cutaneous lupus erythematosus.

Project description:BackgroundPrevious studies have suggested that patients with cutaneous lupus erythematosus (CLE) are deficient in sunscreen use. Use of other photoprotective methods by patients with CLE has not been assessed to our knowledge.ObjectiveWe sought to identify demographic and clinical characteristics of patients with CLE who have the lowest overall sun-protection habits scores, and who are least likely to practice 5 individual photoprotective methods (ie, shade, sunscreen, long sleeves, hat, and sunglasses).MethodsA total of 105 patients with CLE at the University of Texas Southwestern Medical Center in Dallas completed a survey to evaluate their photoprotective practices. Additional information including demographics and clinical indicators related to CLE was collected from the patients.ResultsPatients with medium and dark skin (ie, Fitzpatrick skin types III-VI) and patients aged 31 to 50 years were the least likely CLE subgroups to practice overall photoprotection, as indicated by low sun-protection habits scores (P = .001 and P = .04, respectively). In terms of individual photoprotective methods, male patients with CLE were deficient in sunscreen use, but were more likely to wear hats than female patients with CLE. Sunscreen and sunglasses use was also significantly more infrequent in dark-skinned patients than those with Fitzpatrick skin types I to IV. Patients with CLE between the ages of 41 and 50 years were least likely to wear hats.LimitationsThis study was subject to reporter bias and did not cover barriers to and knowledge of photoprotection.ConclusionCultural customs and misconceptions shared by those from the general population have a significant influence on the photoprotective habits of this CLE population. These need to be addressed to improve photoprotection rates in these at-risk individuals.

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Cutaneous Lupus Erythematosus: Current and Future Pathogenesis-Directed Therapies.

Project description:Cutaneous lupus erythematosus (CLE) is an autoimmune disease of the skin with significant morbidity. Current treatments are often inadequate to control disease and there are no Food and Drug Administration (FDA)-approved therapies for this potentially debilitating disease, underscoring an unmet medical need. Recent insights into disease pathogenesis have implicated innate and adaptive immune components, including type I and type III interferons in the development of CLE. Promising clinical trials based on these insights are now underway. However, the full spectrum of immune cells, cytokines, and environmental triggers contributing to disease remain to be elucidated. In this review, we will highlight the current understanding of CLE immunopathogenesis, the ongoing clinical trial landscape, and provide a framework for designing future therapeutic strategies for CLE based on new insights into disease pathogenesis.

| S-EPMC7087060 | biostudies-literature

Systematic Review: Monoclonal Antibody-Induced Subacute Cutaneous Lupus Erythematosus.

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Genetic epidemiology: systemic lupus erythematosus.

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MicroRNAs in Several Cutaneous Autoimmune Diseases: Psoriasis, Cutaneous Lupus Erythematosus and Atopic Dermatitis.

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