Deep Phenotyping of Cutaneous Lupus Erythematosus
- Conditions
- Cutaneous Lupus Erythematosus
- Interventions
- Registration Number
- NCT06411106
- Lead Sponsor
- Centre for Human Drug Research, Netherlands
- Brief Summary
Cutaneous lupus erythematosus (CLE) is an autoimmune disease of which the pathogenesis and pathophysiology are not fully understood. Given the complex and heterogeneous character of the disease, identification, and development of specific biomarkers for diagnosis, disease subtyping, disease severity, and treatment response in CLE is challenging. Therefore, the main objective of the current study is to further characterize CLE by using a deep phenotyping approach. Moreover, the role of TLR7 activation in the pathophysiology of the various clinical subtypes of CLE will be specifically studied. With this approach the investigators aim to characterize objectively measured disease characteristics and detect novel biomarkers for CLE(-subtypes).
- Detailed Description
Cutaneous lupus erythematosus (CLE) is a rare but burdensome autoimmune disease that includes various subtypes including acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), intermittent cutaneous LE (ICLE) i.e., lupus tumidus (LET) and chronic cutaneous LE (CCLE). These subtypes differ in lesion morphology and histopathology, however disease stratification is often a challenge.
Knowledge on mechanisms involved in the pathogenesis and pathophysiology of CLE is growing, however much remains unknown. The current concept regarding the onset of the disease comprises a genetic background predisposing to CLE triggered by factors such as UV light, what leads to cellular stress and eventually to the release of DNA components in keratinocytes (Fetter et al., 2022). Activation of both Toll-like receptor (TLR)-dependent and TLR-independent inflammatory signalling cascades leads to increased expression of several cytokines, in particular type I interferon (IFN). Type I interferon mediates increased expression of proinflammatory chemokines via the JAK-STAT pathway, leading to recruitment of immune cells, release of cytokines and a chronic reactivation of innate immune pathways.
Findings on the pathogenesis of the disease have led to the development of several targeted therapies that are currently being investigated in clinical trials. However, blockage of one important pathway might not suffice for decreasing disease activity given the limited efficacy of selective IFN antibodies in clinical trials (Kalunian et al., 2016), (Khamashta et al., 2016) (Werth et al., 2017).
Only few biomarkers for CLE have been validated and widely incorporated into clinical practice (Zhu et al., 2021). Type I interferon-inducible proteins can be potentially used to assess disease severity of SCLE and CDLE (Braunstein et al., 2013). Furthermore, low complement in CLE patients may be related to poor prognosis and increased risk of developing systemic disease (Vera et al., 2010) (Vera et al., 2010).
Therefore, the objectives of the current study are to evaluate disease-related characteristics in CLE patients and to evaluate the variability between patients using a deep phenotyping approach, and to investigate the immune response of CLE patients following an ex vivo and in vivo imiquimod skin challenge. The study consists of an observational (part A) and interventional (part B) part in CLE patients and healthy volunteers.- With this approach the investigators aim to characterize objectively measured disease characteristics and detect novel biomarkers for CLE(-subtypes).
This study is part of the Next Generation Immuno Dermatology consortium SKINERGY trials.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm IMIQUIMOD cream 50mg/g CDLE patients and healthy volunteers In part B of this study, 5 mg imiquimod (100 mg Aldara®) per skin area (in total two skin areas) will be applied for two consecutive days under occlusion.
- Primary Outcome Measures
Name Time Method Skin punch biopsies Day 15 Skin punch biopsies (4mm) will be taken from (non-)lesional skin and healthy for histology and RNA-sequencing analysis.
3D Multispectral imaging Day 1 - 15 The redness and superficial morphology of (non-)lesional skin sites and healthy skin will be determined using a 3D multispectral imaging system.
Laser Speckle Contrast Imaging (LSCI) Day 1 - 15 The cutaneous microcirculation of (non-)lesional skin sites and healthy skin will be monitored over a 40 second timespan with a laser speckle contrast imager.
Interferon (IFN) signature Day 15 Blood will be drawn using a venipuncture and analyzed for gene expression related to interferon (IFN).
Skin barrier function by Trans-Epidermal Water Loss (TEWL) Day 1 - 15 The barrier status by trans epidermal water loss of (non-)lesional skin and healthy skin will be determined using TEWL.
Lipidomics of the stratum corneum and OLINK Day 15 Tape stripping will be performed on (non-)lesional skin and healthy skin for extraction of lipids for analysis and analysis will be performed using OLINK.
Cutaneous microbiome Day 15 The cutaneous microbiome of (non-)lesional skin and healthy skin is collected by swabbing.
Blister immune cell subsets Day 15 Blisters will be induced on the (non-)lesional skin and healthy skin, and the blister fluid will be aspirated. The blister fluid will be analyzed for the presence of immune cells using flow cytometry.
Circulating cytokines Day 15 Blood will be drawn using a venipuncture and analyzed for cytokines.
Line-Field Confocal Optical Coherence Tomography (LC-OCT) Day 1 - 15 LC-OCT is a non-invasive optical imaging technique based on a combination of the optical principles of optical coherence tomography and reflectance confocal microscopy with line-field illumination, which can generate cell-resolved images of the skin, in vivo, in vertical section, horizontal section and in three dimensions.
User experience and subjective burden questionnaire Day 15 Measures the user experience and subjective burden of the different assessments performed in this study.
Faecal microbiome (optional for patients) Day 15 The bacterial composition of a stool samples will be determined.
- Secondary Outcome Measures
Name Time Method Patient reported outcomes Day 1- 4 (Part B) Patients will be asked to report on their itch and pain using a Numeric Rating Scale (NRS).
In vivo response to imiquimod Day 1 - 4 (Part B) After topical application of imiquimod for 2 consecutive days, the skin response will be assessed by imaging techniques (multispectral 3D, 2D, LSCI, LC OCT and TEWL) and a skin punch biopsy will be collected 48h after the first application. Blood for circulating cytokine analysis, complement, and autoantibodies will be collected and compared to the baseline sample (taken during part A).
Ex vivo response to imiquimod Day 15 Blood will be collected at one timepoint and stimulated ex vivo with imiquimod for cytokine analysis.
Trial Locations
- Locations (1)
Centre for Human Drug Research
🇳🇱Leiden, Zuid-Holland, Netherlands