Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis.
Ontology highlight
ABSTRACT:
SUBMITTER: Garelli CJ
PROVIDER: S-EPMC7343764 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis.
Garelli Colton J CJ Refat Maggi Ahmed MA Nanaware Padma P PP Ramirez-Ortiz Zaida G ZG Rashighi Mehdi M Richmond Jillian M JM
Frontiers in immunology 20200702
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 treatm ...[more]
Similar Datasets
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
Project description:Purpose of reviewCutaneous lupus erythematosus (CLE) is a highly heterogeneous autoimmune disease. No specific Federal Drug Administration-approved therapies for CLE-alone are available, and resistance to conventional treatments is common. This review will summarize current treatment approaches and pending treatment strategies.Recent findingsResearch into the pathogenesis of CLE is accelerating. A skewed type I interferon production and response contribute to CLE lesions. The pathophysiology of lesions may be similar among the lesional subtypes, and patients with a more TLR9-driven disease mechanism may have more benefit from hydroxychloroquine. Case reports continue to support the use of dapsone for CLE, especially bullous lupus erythematosus. Rituximab and Belimumab have efficacy in patients with systemic lupus erythematosus and severe active CLE. The significant role for type I interferons in CLE and encouraging clinical data suggest anifrolumab as a very promising agent for CLE. Dapirolizumab, BIIB059, Ustekinumab and Janus kinase inhibitors also have supportive early data as promising new strategies for CLE treatment.SummaryContinued research to understand the mechanisms driving CLE will facilitate the development and approval of new targets. The pipeline for new treatments is rich.
| S-EPMC7357847 | biostudies-literature
Project description:Cutaneous lupus erythematosus (CLE) is an interferon (IFN)-driven autoimmune disease that may be limited to the skin or can be associated with systemic lupus erythematosus (SLE). CLE occurs in several morphologic subtypes ranging from isolated, disc-shaped plaques to disseminated skin lesions. The typical histopathologic pattern of skin lesions is named interface dermatitis and characterized by a lymphocytic infiltrate and necroptotic keratinocytes at the dermo-epidermal junction. Other histopathologic patterns primarily involve the dermis or subcutis, depending on the subtype. One critical mechanism in CLE is the chronic reactivation of innate and adaptive immune pathways. An important step in this process is the recognition of endogenous nucleic acids released from dying cells by various pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and other cytosolic receptors. Crucial cells in CLE pathogenesis comprise plasmacytoid dendritic cells (pDCs) as major producers of type I IFN, T cells exerting cytotoxic effects, and B cells, previously believed to contribute via secretion of autoantibodies. However, B cells are increasingly considered to have additional functions, supported by studies finding them to occur in highest numbers in chronic discoid lupus erythematosus (CDLE), a subtype in which autoantibodies are often absent. More precise knowledge of how CLE subtypes differ pathophysiologically may allow a tailored pharmacotherapy in the future, taking into account the specific molecular signature in relation to the morphologic subtype.
| S-EPMC9196867 | biostudies-literature
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.
| S-EPMC4962329 | biostudies-literature
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
Project description:Lesional skin biopsies were taken from patients with active, untreated lupus skin disease (chronic discoid lupus erythematosus, CDLE, n=6; subacute cutaneous lupus erythematosus, SCLE, n=5). Healthy control specimens (HC) were obtained from healthy skin of 5 patients undergoing plastic surgery. In every case, two 4mm punch biopsies were taken. One was flash-frozen in liquid nitrogen and afterwards processed for mRNA isolation. The second biopsy was fixed in 5% formalin solution overnight, and was proceeded for histological investigation.The one-color Agilent 60-mer oligo microarray (Agilent, Santa Clara, CA) was used for gene expression analyses. Statistical analyses were performed using the Agilent Feature Extraction Software⢠and the Rosetta Resolver⢠gene expression data analysis system. The presented gene list (Table S1) includes normalized sample/ control log10-ratios (expression > 2-fold enhanced, p<0.01).
2017-02-24 | E-MTAB-5542 | biostudies-arrayexpress
Project description:Dysfunction of immune systems, including innate and adaptive immunity, is responsible for the immunopathogenesis of systemic lupus erythematosus (SLE). NK cells are a major part of the innate immune system, and diminished populations of NK cells have been reported in SLE patients. However, the mechanisms behind this decrease and the role of NK cells in SLE pathogenesis remain poorly understood. In this study, we found that a deficiency of NK cells, especially CD226(+) NK cells, is prominent in patients with active SLE. Meanwhile, expression of the CD226 ligands CD112 and CD155 on plasmacytoid dendritic cells is observed in SLE patients; thus, activation of CD226(+) NK cells may be induced by CD226-ligand interactions. Furthermore, IFN-?, which is mainly produced by plasmacytoid dendritic cells, can mediate the activation-induced cell death of NK cells. Therefore, these processes likely contribute to the loss of NK cells in patients with active SLE. Despite the impaired cytotoxicity of peripheral NK cells in human SLE patients and mouse SLE models, we provide evidence that CD226(+) NK cells infiltrate the kidneys of predisease MRL-lpr/lpr mice. Kidney-infiltrating NK cells displayed an activated phenotype and a marked ability to produce cytotoxic granules. These results suggest that, before apoptosis, activated NK cells can infiltrate tissues and, to some extent, mediate tissue injury by producing cytotoxic granules and immunoregulatory cytokines.
| S-EPMC3097030 | biostudies-literature
Project description: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.
| S-EPMC9201079 | biostudies-literature
Project description: Not available
| S-EPMC8092459 | biostudies-literature
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.
| S-EPMC3657339 | biostudies-literature