scholarly journals THU0010 GENES ASSOCIATED WITH NUCLEOTIDE OLIGOMERIZATION DOMAIN-LIKE RECEPTOR SIGNALING PATHWAY ARE UPREGULATED IN CUTANEOUS LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 217.3-217
Author(s):  
I. Calderon ◽  
R. Mina
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Innate Immune System ◽  
Cutaneous Lupus Erythematosus ◽  
Skin Lesions ◽  
Innate Immune ◽  
Normal Controls ◽  
Cutaneous Lupus ◽  
Skin Samples

Background:Cutaneous Lupus Erythematosus (CLE) is a disfiguring autoimmune skin disorder with several subtypes: discoid lupus, subacute cutaneous lupus, and acute cutaneous lupus. CLE is associated with defects in the adaptive immune system, and, at times, systemic involvement. The innate immune system is likely involved as seen in the presence of interface dermatitis, which is observed in viral exanthems, and improvement of CLE using inhibitors to membrane-bound Pattern Recognition Receptors.Objectives:Compare the expression of genes associated with the innate immune system in active CLE skin lesions of different subtypes compared to normal skin controls.Methods:Five datasets selected from the Gene Expression Omnibus (GEO) were analyzed using GEO2R to compare the gene expressions between different subtypes of CLE. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, Gene Card, and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis were used to identify the interaction and function of specific genes.Results:There were a total of 147 CLE skin samples and 52 normal controls. Genes associated with the Nucleotide-Binding Oligomerization Domain-Like Receptor (NLR) signaling pathway were upregulated in CLE skin samples (adjusted p-value < 0.001). Five genes associated with the NLR signaling pathway, STAT1, OAS1, OAS2, OAS3, and AIM2, were found to be upregulated in skin samples of CLE patients in all datasets, regardless of type, compared to normal controls in all datasets. These five genes are associated with transcription activation, regulation of viral infection, and interferon response.Conclusion:Genes associated with the NLR signaling pathway are upregulated in the skin lesions of CLE patients compared to normal controls, supporting the role of the innate immune system in CLE. Further validation studies using experimental methods are needed.References:[1]Enhanced inflammasome activity in systemic lupus erythematosus is mediated via type I interferon upregulation of interferon regulatory factor 1. Liu J, et al. Arth Rheum. 2017; 69(9): 1840-1849.Disclosure of Interests:None declared

The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus

Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1510-1517 ◽  
Author(s):  
P Salphale ◽  
D Danda ◽  
L Chandrashekar ◽  
D Peter ◽  
N Jayaseeli ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Severity Index ◽  
Skin Lesions ◽  
Systemic Lupus ◽  
Disease Area ◽  
Indian Patients ◽  
The Mean ◽  
Cutaneous Lupus

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a newly described tool used to assess the activity of and damage caused by cutaneous lupus erythematosus (CLE). There is a paucity of data on CLASI from the Indian subcontinent. We sought to determine the applicability of CLASI in specific lesions of CLE in patients with systemic lupus erythematosus (SLE) attending a tertiary care hospital in India. In this prospective, cross-sectional study, 93 patients of SLE with cutaneous lesions were recruited. CLASI activity and damage scores of lupus erythematosus (LE)-specific skin lesions were done in 75 patients with SLE. The mean CLASI activity score was 15.4 ± 9.4 (range 0–39) and the mean damage score was 6.87 ± 7.75 (range 0–30). Higher mean CLASI activity scores were seen in patients with a combination of acute, subacute and chronic CLE and in those with widespread lesions. Patients with longstanding disease and long duration of skin lesions had higher damage scores. This study shows that CLASI is an effective tool to assess cutaneous activity of LE-specific lesions, and the damage caused by them, in Indian patients.

scholarly journals Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus

2007 ◽  
Vol 56 (6) ◽  
pp. 1910-1920 ◽  
Author(s):  
B. Franz ◽  
B. Fritzsching ◽  
A. Riehl ◽  
N. Oberle ◽  
C.-D. Klemke ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Skin Lesions ◽  
Cutaneous Lupus

The innate immune system in human systemic lupus erythematosus

2017 ◽  
Vol 131 (8) ◽  
pp. 625-634 ◽  
Author(s):  
Marc Weidenbusch ◽  
Onkar P. Kulkarni ◽  
Hans-Joachim Anders
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Innate Immune System ◽  
Innate Immune ◽  
Type I ◽  
Human Systemic Lupus Erythematosus ◽  
Systemic Lupus ◽  
Adaptive Immune

Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease. This is why targeting the innate immune system offers an additional means of treating SLE. First trials assessing the efficacy of anti-type I interferon (IFN) therapy or modulators of pattern recognition receptor (PRR) signalling have been attempted. In this review, we summarize the available evidence on the role of several distinct innate immune elements, especially neutrophils and dendritic cells as well as the IFN system, as well as specific innate PRRs along with their signalling pathways. Finally, we highlight recent clinical trials in SLE addressing one or more of the aforementioned components of the innate immune system.

Photosensitivity, phototesting, and photoprotection in cutaneous lupus erythematosus

Lupus ◽  
2010 ◽  
Vol 19 (9) ◽  
pp. 1036-1046 ◽  
Author(s):  
A. Kuhn ◽  
V. Ruland ◽  
G. Bonsmann
Keyword(s):  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Cutaneous Lupus Erythematosus ◽  
Sun Exposure ◽  
Skin Lesions ◽  
Cellular Adhesion ◽  
Cellular Adhesion Molecules ◽  
Cytokines And Chemokines ◽  
Mediators Of Inflammation ◽  
Cutaneous Lupus

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease involving well-defined skin lesions that can be categorized as acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), or intermittent CLE (ICLE). It is commonly accepted that ultraviolet (UV) exposure can induce and exacerbate skin lesions in patients with certain subtypes of CLE. Phototesting with UVA and UVB irradiation using a standardized protocol has proven to be a reliable model to study photosensitivity in CLE and to analyse the underlying pathomechanisms of the disease. In addition to UV-mediated induction of apoptosis, the molecular and cellular factors that may underlie the abnormal long-lasting photoreactivity in CLE include mediators of inflammation such as cytokines and chemokines, inducible nitric oxide (NO) synthase (iNOS), and cellular adhesion molecules. The photosensitivity associated with CLE requires education of the patient about avoidance of excessive sun exposure, continuous photoprotection through physical measures such as protective clothing, and daily application of broad-spectrum sunscreens. Novel approaches to UV-protection, such as alpha-MSH or thymidine dinucleotides, might also have an impact on photosensitivity in patients with CLE. In this review, we summarize the current knowledge about photosensitivity in patients with CLE, including an overview of standardized phototesting procedures, possible molecular pathomechanisms, and photoprotection. Lupus (2010) 19, 1036—1046.

scholarly journals Proteome Study of Cutaneous Lupus Erythematosus (CLE) and Dermatomyositis Skin Lesions Reveals IL-16 Is Differentially Upregulated in CLE

2021 ◽  
Author(s):  
Timothy B. Niewold ◽  
Alexander Meves ◽  
Julia S. Lehman ◽  
Karin Popovic-Silwerfeldt ◽  
Aliisa Häyry ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Lupus Erythematosus ◽  
Caspase 3 ◽  
Active Form ◽  
Cutaneous Lupus Erythematosus ◽  
Skin Lesions ◽  
Differential Diagnostics ◽  
Skin Biopsies ◽  
Inflammatory Infiltrates ◽  
Cutaneous Lupus

Abstract Background: The objective of the study was to explore disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). Methods: Skin biopsies acquired from active CLE and DM lesions, patient (PC) and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist and inflammatory foci were laser micro-dissected, captured and proteins within captured tissue were detected in a hypothesis free manner by mass-spectrometry. Protein pathway analysis was performed by string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC).Results: Proteome investigation identified interleukin (IL)-16 to be the only detectable and abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16 and Caspase-3 positive cells were identified in CLE lesions in comparison to DM, PC and HC. Interferon-regulated proteins (IRP) were abundant in both CLE and DM. Proteomic results indicate more abundant complement deposition in CLE skin lesions. Conclusions: Using hypothesis free mass-spectrometry investigation of CLE inflammatory infiltrates, we identified that IL-16 is the only detectable and highly abundant cytokine, while IRP was a common feature of both CLE and DM. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. Potentially, IL-16 could be of interest as a future therapeutic target for CLE.

The devil's in the dosing: severe drug-induced liver injury in a hydroxychloroquine-naive patient with subacute cutaneous lupus erythematosus and porphyria cutanea tarda

Lupus ◽  
2018 ◽  
Vol 27 (8) ◽  
pp. 1383-1386 ◽  
Author(s):  
B Sunkara ◽  
D Roofeh ◽  
S Silver ◽  
T LeBleu Pearson ◽  
M Ettel ◽  
...  
Keyword(s):  
Liver Injury ◽  
Lupus Erythematosus ◽  
Porphyria Cutanea Tarda ◽  
Cutaneous Lupus Erythematosus ◽  
Antibody Test ◽  
Skin Lesions ◽  
Drug Induced ◽  
Naive Patient ◽  
Drug Induced Liver Injury ◽  
Cutaneous Lupus

A 29-year-old woman with a 1.5 year history of photosensitive skin lesions on her hands presented with a malar rash, bullous lesions on her hands, and was diagnosed with subacute lupus erythematosus after serologies revealed a positive antinuclear antibody test (1:2560), and antibodies to Ro/SSA and dsDNA. Hydroxychloroquine (400 mg/day) was prescribed and the patient developed severe drug-induced liver injury. Biopsy of her bullous skin lesions was consistent with porphyria cutanea tarda, as were her serological and urinary exams. She was successfully treated with therapeutic phlebotomy. This case identifies porphyria cutanea tarda as an important differential diagnosis for the rheumatologist to consider when evaluating patients with bullous skin lesions. Hydroxychloroquine in lower doses is an effective treatment for porphyria cutanea tarda; at doses used to treat systemic lupus erythematosus and subacute cutaneous lupus, there is a potentially life-threatening complication of hepatotoxicity.

Selective Expansions of T cells Expressing Vβ38 and Vβ13 in Skin Lesions of Patients with Chronic Cutaneous Lupus Erythematosus

1996 ◽  
Vol 23 (10) ◽  
pp. 670-676 ◽  
Author(s):  
Fukumi Furukawa ◽  
Yoshiki Tokura ◽  
Kayo Matsushita ◽  
Kayoko Iwasaki-Inuzuka ◽  
Kazue Onagi-Suzuki ◽  
...  
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Skin Lesions ◽  
Cutaneous Lupus

Subacute Cutaneous Lupus Erythematosus Induced by Nifedipine

2003 ◽  
Vol 7 (3) ◽  
pp. 243-246 ◽  
Author(s):  
Emanuela Gubinelli ◽  
Barbara Cocuroccia ◽  
Giampiero Girolomoni
Keyword(s):  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Skin Lesions ◽  
Channel Blockers ◽  
Subacute Cutaneous Lupus Erythematosus ◽  
Rapid Improvement ◽  
Drug Induced ◽  
Dermoepidermal Junction ◽  
Antihistone Antibody ◽  
Cutaneous Lupus

Background: Subacute cutaneous lupus erythematosus (SCLE) has been reported to be associated with the use of several drugs, including thiazides, terbinafine, and, rarely, calcium channel blockers. Objective: A case of SCLE induced by nifedipine is presented. Methods and Results: A 48-year-old white woman developed a papulosquamous and annular eruption in sun-exposed areas during the summer. The patient was taking nifedipine for essential hypertension for four years. Serology showed the presence of antinuclear and anti-Ro/SSA as well as antihistone antibodies. Histopathologic and immunopathologic (granular IgM deposits at the dermoepidermal junction) findings confirmed the diagnosis of SCLE. Nifedipine discontinuation led to rapid improvement with almost complete resolution of skin lesions in one month in the absence of active treatment. Reduction of antinuclear, anti-Ro/SSA, and antihistone antibody levels was documented after six months. Conclusion: Nifedipine can cause SCLE after a long period of administration. Antihistone antibodies may be associated with drug-induced SCLE.

Gemcitabine-Induced Subacute Cutaneous Lupus Erythematosus: A Case Report

Chemotherapy ◽  
2016 ◽  
Vol 61 (5) ◽  
pp. 236-239 ◽  
Author(s):  
Masha Ben Zvi ◽  
Hananya Vaknine ◽  
Joseph Menczer ◽  
Ofri Peled ◽  
Erez Ben Shem ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Recurrent Ovarian Cancer ◽  
Skin Lesions ◽  
Steroid Treatment ◽  
Oral Steroid ◽  
Subacute Cutaneous Lupus Erythematosus ◽  
Chemotherapy Agents ◽  
Cutaneous Lupus

Subacute cutaneous lupus erythematosus (SCLE) is a rare eruption related to several pharmacological and chemotherapy agents. We present a 63-year-old female with recurrent epithelial ovarian cancer who developed SCLE after administration of gemcitabine. Following discontinuation of gemcitabine and after oral steroid treatment, all skin lesions disappeared. In view of the extensive use of gemcitabine in recurrent ovarian cancer, it is important to be aware of the possibility of SCLE occurrence in these patients.

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