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

2021 ◽  
Vol 12 ◽  
Author(s):  
Lisa Abernathy-Close ◽  
Stephanie Lazar ◽  
Jasmine Stannard ◽  
Lam C. Tsoi ◽  
Sean Eddy ◽  
...  
Keyword(s):  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Cutaneous Lupus Erythematosus ◽  
Discoid Lupus Erythematosus ◽  
Type I ◽  
Systemic Lupus ◽  
Cutaneous Inflammation ◽  
Cutaneous Lupus

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.

Expression pattern of tissue-resident memory T cells in cutaneous lupus erythematosus

Lupus ◽  
2021 ◽  
pp. 096120332110172
Author(s):  
Hyeon-Jung Gu ◽  
Shinyoung Song ◽  
Joo Young Roh ◽  
YunJae Jung ◽  
Hee Joo Kim
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
Memory T Cells ◽  
Cutaneous Lupus Erythematosus ◽  
Discoid Lupus Erythematosus ◽  
Type I ◽  
Systemic Lupus ◽  
Peripheral Tissues ◽  
Resident Memory T Cells ◽  
Cutaneous Lupus

Background Tissue resident memory T cells (TRMs) persist long-term in peripheral tissues without recirculation, triggering an immediate protective inflammatory state upon the re-recognition of the antigen. Despite evidence incriminating the dysregulation of TRMs in autoimmune diseases, few studies have examined their expression in cutaneous lupus erythematosus (CLE). Objectives We aimed to examine whether there are differences among TRM populations in CLE depending on different clinical conditions, such as the CLE subtype or association with systemic lupus erythematosus, and to determine the effect of type I interferon (IFN) on the development of TRMs in CLE. Methods CLE disease activity was evaluated using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. The expression of the TRM markers CD69 and CD103 in CLE lesions was evaluated by immunofluorescence. Flow cytometry was performed on peripheral blood mononuclear cells after IFNα treatment. Results The number of TRMs expressing either CD69 or CD103 was significantly higher in CLE lesions than in control skin; however, it was not significantly different between discoid lupus erythematosus and subacute CLE, or dependent on the presence of concomitant systemic lupus. Lesional severity was not correlated with an increase in TRMs in CLE. IFNα treatment induced a conspicuous increase in CD69 expression in skin-homing T cells, more profoundly in CD4+ T cells than in CD8+ T cells. Conclusions Skin TRMs, either CD69 or CD103-positive cells, showed increased levels in the lesional skin of CLE, and IFNα increased the expression of CD69 in T cells.

Spectrum of cutaneous lupus erythematosus in South Africans with systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (8) ◽  
pp. 1021-1026 ◽  
Author(s):  
K Koch ◽  
M Tikly
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
Odds Ratio ◽  
Systemic Disease ◽  
Cutaneous Lupus Erythematosus ◽  
Discoid Lupus Erythematosus ◽  
Systemic Lupus ◽  
South Africans ◽  
Cutaneous Lupus

Background Cutaneous involvement is very common in systemic lupus erythematosus. We describe the prevalence and spectrum of lupus-specific (cutaneous lupus erythematosus) and non-specific cutaneous features amongst mostly black South Africans with systemic lupus erythematosus. Patients and methods A retrospective record review of 298 South Africans (262 blacks and 36 non-blacks) with systemic lupus erythematosus was carried out. Cutaneous features were classified according to the Gilliam and Sontheimer classification of cutaneous lupus. Results Most (81.5%) patients were black African females. The mean (SD) age at diagnosis and follow-up duration were 35.0 (11.8) and 8.0 (5.9) years, respectively. Cutaneous lupus erythematosus was seen in 76.1% of patients, mainly chronic cutaneous lupus erythematosus with the discoid lupus erythematosus subtype seen in 52.1% of patients. Acute cutaneous lupus erythematosus was seen in 30.2% of patients and was more common in non-blacks than blacks (odds ratio = 3.8 (1.9–7.9)); localized acute cutaneous lupus erythematosus was more common than generalized acute cutaneous lupus erythematosus (odds ratio = 2.6 (1.6–4.4)). Non-specific cutaneous features occurred in 77.2%, with oral/nasal ulcers and Raynaud’s phenomenon each occurring in approximately 40% of patients. Diffuse melanonychia at initial diagnosis was present in 37.4% of patients and was more common in blacks than non-blacks (odds ratio = 3.1 (1.3–7.3)). Acute cutaneous lupus erythematosus was associated with renal disease (odds ratio = 2.8 (1.6–4.7)) and chronic cutaneous lupus erythematosus with arthritis (odds ratio = 2.02 (1.24–3.29)). Diffuse melanonychia was associated with less renal disease and anti-dsDNA antibody positivity (odds ratio = 0.4 (0.3–0.7) and 0.4 (0.2–0.6), respectively) and significantly lower lupus severity index scores (mean (SD) = 5.99 (1.11) vs 6.56 (1.36) in patients with no melanonychia, p < 0.05)). Conclusion In this study of South Africans with systemic lupus erythematosus, the skin was the most commonly affected organ. In general, cutaneous lupus erythematosus was associated with less severe systemic disease. Acute cutaneous lupus erythematosus was less common in blacks, whereas discoid lupus erythematosus was more common than reported in Caucasians. Diffuse melanonychia was a distinctive finding and was associated with milder systemic disease.

scholarly journals Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes

2019 ◽  
Vol 8 (8) ◽  
pp. 1244 ◽  
Author(s):  
Celine C. Berthier ◽  
Lam C. Tsoi ◽  
Tamra J. Reed ◽  
Jasmine N. Stannard ◽  
Emily M. Myers ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Discoid Lupus Erythematosus ◽  
Type I ◽  
Systemic Involvement ◽  
Ifn Γ ◽  
Therapeutic Decision Making ◽  
Cutaneous Lupus

Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates cutaneous lupus subtypes is limited. Here, we utilized a large cohort of 90 CLE lesional biopsies to compare discoid lupus erythematosus (DLE) and subacute cutaneous lupus (SCLE) in patients with and without associated SLE in order to discern the drivers of disease activity and possibly uncover better treatment targets. Overall, we found that DLE and SCLE share many differentially expressed genes (DEG) reflecting type I interferon (IFN) signaling and repression of EGFR pathways. No differences between CLE only and SLE-associated CLE lesions were found. Of note, DLE uniquely expresses an IFN-γ node. Unbiased cluster analysis of the DEGs identified two groups separated by neutrophilic vs. monocytic signatures that did not sort the patients based on clinical phenotype or disease activity. This suggests that unbiased analysis of the pathobiology of CLE lesions may be important for personalized medicine and targeted therapeutic decision making.

scholarly journals OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

scholarly journals Ocular Complications in Cutaneous Lupus Erythematosus: A Systematic Review with a Meta-Analysis of Reported Cases

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
L. Arrico ◽  
A. Abbouda ◽  
I. Abicca ◽  
R. Malagola
Keyword(s):  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Correct Diagnosis ◽  
Cutaneous Lupus Erythematosus ◽  
Discoid Lupus Erythematosus ◽  
Systemic Lupus ◽  
Ocular Complications ◽  
Ocular Symptoms ◽  
Inflammatory Syndrome ◽  
Cutaneous Lupus

Ocular complications associated with cutaneous lupus erythematosus (CLE) are less studied compared with those ones associated with systemic lupus erythematosus (SLE). The main ocular sites involved in patients affected by discoid lupus erythematosus (DLE) are eyelids followed by orbit and periorbit, the least being cornea. The most common complications are blepharitis usually affecting the lower lid and associated with some type of lid lesion such as plaque or erythematosus patches and madarosis. Few cases with LE profundus (LEP) and ocular complications are reported, but they are associated with orbital inflammatory syndrome and severe complications. The main treatment prescribed is hydroxychloroquine with a dose of 200 mg twice a day for 6 to 8 weeks. Corticosteroids are also used. Intervals between the correct diagnosis and the beginning of the ocular symptoms are commonly delayed. Ophthalmologist should be aware of the ocular manifestation of this autoimmune disease.

Evaluation of the Incidence of Discoid Lupus Erythematosus in Patients with Systemic Lupus Erythematosus and Its Relationship to Disease Activity

2014 ◽  
Vol 18 (5) ◽  
pp. 316-319 ◽  
Author(s):  
Massoud Saghafi ◽  
Kamila Hashemzadeh ◽  
Sima Sedighi ◽  
Mohammad Javad Yazdanpanah ◽  
Zahra Rezaieyazdi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Systemic Disease ◽  
Severe Disease ◽  
Discoid Lupus Erythematosus ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Cutaneous Manifestations

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with wide clinical features ranging from cutaneous manifestations to systemic disease. Skin is one of the most commonly affected organs in SLE. Objective: To determine whether there is any correlation between discoid lupus erythematosus (DLE) and the severity of SLE. Methods: In a prospective cross-sectional study, 60 consecutive patients with newly diagnosed SLE were enrolled. Skin biopsy was performed to establish the diagnosis of DLE. Disease activity was determined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). A SLEDAI-2K score ≥ 10 was considered active and severe disease. Results: Eleven SLE patients (9 females and 2 males) had DLE (18.3%) and 49 patients (46 females and 3 males) had SLE without DLE (81.7%). The mean age of patients with DLE was 30.18 ± 11.07 years and in patients without it was 28.4 ± 10.26 years ( p = .6). Three of 11 patients with DLE (27.3%) and 14 of 49 patients without DLE (28.6%) had a SLEDAI-2K score ≥ 10 ( p = 1). Conclusion: The presence of DLE in our patients with SLE was not associated with less severe disease.

scholarly journals Monitoring of serum TWEAK levels guides glucocorticoid dosages in the treatment of systemic lupus erythematosus

2019 ◽  
Author(s):  
Jingyun Chen ◽  
Huixia Wang ◽  
Yi Wu ◽  
Xiaokang Wu ◽  
Li Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
White Blood Cells ◽  
Cutaneous Lupus Erythematosus ◽  
Glucocorticoid Therapy ◽  
Discoid Lupus Erythematosus ◽  
Systemic Lupus ◽  
Serum Samples

Abstract Background Accurate assessment of systemic lupus erythematosus (SLE) disease activity is critical. Currently existing indices or measures for assessment are either expensive, intricate, or inaccurate. The novel indices with higher sensitivity and specificity have become one of the aims of the investigators. This study was designed to explore the relationship between serum tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and systemic lupus erythematosus disease activity index (SLEDAI) as well as its role in guiding glucocorticoid dosages in the treatment of SLE. Of 59 patients with SLE, 20 patients with subacute cutaneous lupus erythematosus (SCLE), 13 patients with discoid lupus erythematosus (DLE) and 32 healthy volunteers, soluble TWEAK level was determined in both serum and urine. Monomeric C-reactive protein, antinuclear antibody, interleukin 6, complements, erythrocyte sedimentation rate, and white blood cells were measured in serum samples. Moreover, SLEDAI-2K was used for evaluating the disease. Finally, methylprednisolone was administrated orally to SLE patients with the doses depending on serum TWEAK levels. Results We found that serum TWEAK levels are higher in patients with SLE (383.0 ± 45.37 ng/ml, p < 0.001 for both) or SCLE (129.1 ± 25.73 ng/ml, p < 0.05 for both) than in patients with DLE (78.38 ± 22.85 ng/ml) or in healthy controls (78.38 ± 22.85 ng/ml). Also, serum TWEAK levels correlate positively with SLEDAI-2K in patients with SLE (r2 = 0.101, p < 0.001), whereas urine TWEAK levels reflect renal damage in patients with lupus nephritis. Moreover, serum TWEAK levels had a higher correlation coefficient with SLEDAI-2K scores compared with the other serum parameters. Furthermore, TWEAK-based glucocorticoid therapy is associated with lower SLEDAI-2K scores and fewer flares in patients with SLE. Conclusions Serum TWEAK is a useful biomarker reflecting SLE disease, and monitoring of serum TWEAK levels can improve the outcomes of glucocorticoid therapy for patients with SLE.

Clinical characteristics of itch in cutaneous lupus erythematosus: A prospective, multicenter, multinational, cross-sectional study

Lupus ◽  
2021 ◽  
pp. 096120332110160
Author(s):  
Dominik Samotij ◽  
Justyna Szczęch ◽  
Emiliano Antiga ◽  
Diletta Bonciani ◽  
Marzia Caproni ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Cross Sectional Study ◽  
Skin Damage ◽  
Sectional Study ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Cutaneous Lupus

Objective Pruritus is an important symptom frequently accompanying various inflammatory skin conditions and some recent data indicated that it may be associated with autoimmune connective tissue diseases. The aim of this study was to assess the frequency and clinical presentation of itch in CLE. Methods A multinational, prospective, cross-sectional study was performed to assess the prevalence, intensity and clinical characteristic of pruritus in various subtypes of CLE. A total of 153 patients with active CLE lesions were included. Their age ranged between 17 and 82 years (mean 49.8 ± 15.4 years), and 115 patients (75.2%) were women. The disease activity and damage were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Pruritus severity was assessed with Numeric Rating Scale (NRS) and the 12-Item Pruritus Severity Scale. Dermatology Life Quality Index and EQ-5D questionnaire were used to measure quality of life. Results Pruritus was present in 116 (76.8%) of patients of whom half had NRS scoring equal or above 4 points indicating moderate or severe pruritus. Most commonly itch was localized on the scalp, face (excluding ears and nose) and arms (40.5%, 36.2%, 31.9%, respectively). Sensations connected with pruritus were most frequently described as burning, tingling and like ants crawling feeling, but 31.9% patients described it as “pure itch”. More than half of patients reported that pruritus was present every day, and it was most frequent during the evenings. The pruritus scoring and the CLASI activity score were significantly correlated (r = 0.42, p = 0.0001), while no correlation was found with the CLASI damage score (p = 0.16). Both the maximum and average itch intensity were correlated with systemic lupus erythematosus (SLE) activity measured with the Systemic Lupus Erythematosus Disease Activity Index. Conclusions Pruritus is a common, but frequently overlooked symptom of CLE. Its intensity correlates with the activity of CLE, but not with the skin damage. In more than a half of patients it occurs on a daily basis. The correlation between the intensity of pruritus and the activity of the skin lesions and the systemic involvement indicate that pruritus could be an individual indicator of both SLE and CLE activity.

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