Lupus Lesions Research Articles

Tumid Lupus Case Report

ABSTRACT Cutaneous lupus erythematosus (CLE) can present with a wide variety of dermatologic manifestations and is broken down into acute, subacute, and chronic subtypes. Tumid lupus, a variant of CLE, is rarely associated with systemic lupus erythematosus. Lesions of CLE and tumid lupus can mimic multiple other dermatologic conditions. We present a case of a patient with tumid lupus who was initially treated for erythema migrans and systemic symptoms suspected to represent Lyme disease. This article is intended for nurse practitioners, nurses, and other clinicians practicing in dermatology, primary care, urgent care, and emergency medicine settings in the care of patients presenting with annular skin lesions.

Lupus dermal fibroblasts are proinflammatory and exhibit a profibrotic phenotype in scarring skin disease.

Fibroblasts are stromal cells known to regulate local immune responses important for wound healing and scar formation; however, the cellular mechanisms driving damage and scarring in patients with cutaneous lupus erythematosus (CLE) remain poorly understood. Dermal fibroblasts in patients with systemic lupus erythematosus (SLE) experience increased cytokine signaling in vivo, but the effect of inflammatory mediators on fibroblast responses in nonscarring versus scarring CLE subtypes is unclear. Here, we examined responses to cytokines in dermal fibroblasts from nonlesional skin of 22 patients with SLE and CLE and 34 individuals acting as healthy controls. Notably, inflammatory cytokine responses were exaggerated in SLE fibroblasts compared with those from individuals acting as healthy controls. In lesional CLE biopsies, these same inflammatory profiles were reflected in single-cell RNA-Seq of SFRP2+ and inflammatory fibroblast subsets, and TGF-β was identified as a critical upstream regulator for inflammatory fibroblasts in scarring discoid lupus lesions. In vitro cytokine stimulation of nonlesional fibroblasts from patients who scar from CLE identified an upregulation of collagens, particularly in response to TGF-β, whereas inflammatory pathways were more prominent in nonscarring patients. Our study revealed that SLE fibroblasts are poised to hyperrespond to inflammation, with differential responses among patients with scarring versus nonscarring disease, providing a potential skin-specific target for mitigating damage.

Systemic lupus erythematosus mimicking retinal migraine: a case report

Background Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines. Case report A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur. Conclusion Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine.

Turkey ear as a cutaneous manifestation of tuberculosis

Lupus vulgaris is the most common morphological variant of cutaneous tuberculosis. Classical lupus lesions are often seen in the head and neck region. Turkey ear is a clinically descriptive term, previously being used for the earlobe with reddish indurated plaque lesions, which recently can be a sign for lupus vulgaris.

Squamous Cell Carcinoma on Discoid Lupus on Photo Protected Area

Introduction: Discoid lupus erythematosus is an autoimmune disease with mainly skin manifestations. Squamous cell carcinoma is a complication of discoid lupus on phototype VI and photoprotected area. We are reporting a case. Observation: It was a 52-year-old man, driver for 30 years, phototype VI, received for a budding lesion of the back evolving for 1 year on discoid lupus erythematosus followed for 10 years. On examination, there was a budding swelling with a bleeding surface of 5cm in diameter resting on a discoid lupus lesion in the lumbar region with discoid plates along the spine. Histology showed moderately differentiated tumor cells with volumeincreased nuclei; nucleolated. He benefited from a carcinological excision followed by chemotherapy and was then lost to follow-up. Discussion: Squamous cell carcinomas are rare on discoid lupus erythematous. The factors incriminated would be chronic inflammatory processes, atrophy, depigmentation, UV rays, microtrauma by friction related to the patient’s profession. Conclusion: Squamous cell carcinoma on discoid lupus erythematous remains a rare cancer in photo protected areas.

Les connectivites en Dermatologie: Une série de 290 cas à Dakar, Sénégal

Introduction: The general objective was to determine the epidemiological, clinical, paraclinical, therapeutic and evolutionary aspects of connectivitis in the dermatology department of the CHU Aristide Le Dantec. Patients and methods: This was a retrospective and descriptive study conducted in the Dermatology Department of the University Hospital Center (UHC) Aristide Le Dantec (HALD) of Dakar between January 2009 and December 2019. Their diagnoses were retained according to the international criteria validated in the course of connectivites Results: We identified 290 cases of connectivitis. Systemic scleroderma was the most frequent in 34.42% (n=94), followed by systemic lupus in 25.86% (n=75), mixed connectivities in 22,06% (n=64) and dermatomyositis in 19,32% (n=56). Cancer was associated with dermatomyositis in 11 cases and with systemic scleroderma in 3 cases. The mean age of our patients was 38.23 years. The sex ratio was 4.2 and the mean duration of evolution was 25 months. Dermatological manifestations were constant, found in all patients. In systemic lupus, they were dominated by discoid lupus lesions found in 40% and hypochromic spots (86%) in systemic scleroderma. In dermatomyositis, skin lesions were dominated by periorbital erythroedema (66.07%). Joint manifestations were found in 56.89% of cases (n= 165), muscular manifestations in 41.37% of cases (n= 120) and pleuropulmonary manifestations in 31.3% of cases (n=91). Neuropsychiatric manifestations were noted in 5.17% of cases (n=15). All our patients were treated with corticosteroid therapy and 12.06% of them had received immunosuppressive treatment, the most commonly used molecules being methotrexate (3.44%) and cyclophosphamide (8.27%). Hydroxychloroquine was prescribed in 59.31% of patients, while D-penicillamine was prescribed in 42.06% of patients, 100% of whom were treated for systemic scleroderma. The main complications encountered were infectious complications in 83 cases (28.6%). Visceral complications, a type of visceral insufficiency, were noted in 4.13% of cases. Conclusion: Our study demonstrates the frequency of connectivitis in the dermatology department. Its particularity was the predominance of systemic scleroderma over lupus which was classically the first connectivite in dermatology services. The delay in diagnosis noted is correlated with visceral attacks; hence the importance of a better knowledge of these affections for an early management.

Rhupus: About 2 Observations and Review of the Literature

Introduction: Rhupus is the combination of manifestations of RA and SLE, meeting the respective classification criteria of these two pathologies. This uncommon clinical entity with a prevalence of about 0.09% was described by Toone in 1960. Objective: To prove the mutual exclusivity of RA and SLE in rhupus. Observation 1: This was a 40-year-old patient, without children, hypertensive on 10mg of nifedipine, followed for 10 years for RA on 15mg of methotrexate. Admitted for polyarthritis, discoid lupus lesions on the ears, facial erythema in vespertilio, oral ulcers, otherwise, the rest of the physical examination was normal. The biological finds hemolytic anemia (hemoglobin to 9.8g/dl), biological inflammatory syndrome (CRP to 101 mg / l), rheumatoid factors, antinuclear antibodies to 1/564 type speckled appearance, U1RNP, anti-Sm and anti-SSA / Ro 52 were positive and hypocomplementemia CH50 to 21.80 (N : 41-94 U / ml). By the classification criteria the diagnosis of rhupus was retained, 400mg of hydroxychloroquine added to his treatment for 6 months gave a favorable evolution. Observation 2: This was a 21-year-old Guinean student living in Dakar who had been treated for RA for 2 years with 15 mg of methotrexate. She consulted for photosensitivity, erythema in the décolleté and the anterior chest and persistent polyarthritis. Antinuclear antibodies at 1/198 in indirect immunofluorescence on Hep20-10 euroimmun slide, anti-double-stranded DNA antibodies at 640U/ml and anti-Sm at 9U/ml were positive. She received 15mg of methotrexate, 400mg of hydroxychloroquine and 10mg of Prednisolone for 6 months which gave a good improvement. Conclusion: Rhupus seems to be underdiagnosed, its existence is a reality to be understood to face the challenge.

Understanding innate immune cell-mediated inflammation in UV-induced skin injury in lupus-prone mice.

Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by sensitivity to ultraviolet (UV) light and overproduction of type I interferons (IFNs), in which skin is affected in up to 70% of total SLE patients. While UV light is one of few well-known triggers of SLE, precise mechanisms governing UV-mediated inflammation are incompletely understood. Our lab recently performed single-cell analysis of cutaneous lupus lesions, showing an increase in activated monocyte-derived CD16+ dendritic cells (DCs) in both lesional and non-lesional skin of lupus patients compared with healthy controls. With the goal of understanding the functionality of this subset, we have turned to lupus-prone murine models. RNA sequencing of UV-exposed skin samples from lupus-prone NZM2328 (NZM), iNZM (lupus-prone mice lacking the type I IFN receptor) and wildtype Balb/c mice demonstrated upregulation of monocyte chemoattractants like CCL2 in NZM greater than iNZM and Balb/c, which was verified at the transcript and protein level of UV-irradiated human lupus keratinocytes compared with healthy controls. We further verified recruitment and differentiation of monocytes into monocyte-derived DCs (moDC) in UV-irradiated skin of NZM, iNZM, and Balb/c mice, as well as increased MHC class II expression in skin-recruited moDCs of chronically UV-exposed NZM mice greater than iNZM and Balb/c, suggesting an importance of type I IFN signaling in this process. Future studies will be directed at understanding mechanisms of monocyte recruitment and differentiation at sites of UV-mediated inflammation, as well as type I IFN effects on moDC antigen uptake and presentation. Supported by grants from NIH (T32-GM007863, R01-AR071384, and K24-AR076975)

Single-cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney.

Cutaneous lupus is commonly present in patients with systemic lupus erythematosus (SLE). T cells have been strongly suspected to contribute to the pathology of cutaneous lupus; however, our understanding of the relevant T cell phenotypes and functions remains incomplete. Here, we present a detailed single-cell RNA-Seq profile of T and NK cell populations present within lesional and nonlesional skin biopsies of patients with cutaneous lupus. T cells across clusters from lesional and nonlesional skin biopsies expressed elevated levels of IFN-simulated genes (ISGs). Compared with T cells from control skin, however, T cells from cutaneous lupus lesions did not show elevated expression profiles of activation, cytotoxicity, or exhaustion. Integrated analyses indicated that skin lymphocytes appeared less activated and lacked the expanded cytotoxic populations prominent in lupus nephritis kidney T/NK cells. Comparison of skin T cells from lupus and systemic sclerosis skin biopsies further revealed an elevated ISG signature specific to cells from lupus biopsies. Overall, these data represent the first detailed transcriptomic analysis to our knowledge of the T and NK cells in cutaneous lupus at the single-cell level and have enabled a cross-tissue comparison that highlights stark differences in composition and activation of T/NK cells in distinct tissues in lupus.

Amelioration of Lupus Serum-Induced Skin Inflammation in CD64-Deficient Mice.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by high autoantibodies levels and multiorgan tissue damage. The current study investigated the role of CD64 in SLE patients and animal models. According to a flow cytometry study, SLE patients showed an increase in CD64 expression in circulating monocytes. There was a correlation between CD64 and SLEDAI, blood urea nitrogen levels, and anti-Sm antibodies. In skin lesions of lupus MRL/lpr mice, there was high IgG deposition and CD64 expression. In vitro, cytokines IL-10 and IFN-γ upregulated CD64 expression in monocytes/macrophages that was inhibited by glucocorticoids. In CD64-deficient mice, skin inflammation induced by lupus serum was reduced. Furthermore, activation of spleen tyrosine kinase (Syk), Akt, and extracellular signal-regulated kinase (Erk) was inhibited in CD64-deficient monocytes. The results suggest that CD64 could be a biomarker for observing SLE progression, as well as a mechanistic checkpoint in lupus pathogenesis.

DOCK8-expressing T follicular helper cells newly generated beyond self-organized criticality cause systemic lupus erythematosus

SummaryPathogens including autoantigens all failed to induce systemic lupus erythematosus (SLE). We, instead, studied the integrity of host's immune response that recognized pathogen. By stimulating TCR with an antigen repeatedly to levels that surpass host's steady-state response, self-organized criticality, SLE was induced in mice normally not prone to autoimmunity, wherein T follicular helper (Tfh) cells expressing the guanine nucleotide exchange factor DOCK8 on the cell surface were newly generated. DOCK8+Tfh cells passed through TCR re-revision and induced varieties of autoantibody and lupus lesions. They existed in splenic red pulp and peripheral blood of active lupus patients, which subsequently declined after therapy. Autoantibodies and disease were healed by anti-DOCK8 antibody in the mice including SLE-model (NZBxNZW) F1 mice. Thus, DOCK8+Tfh cells generated after repeated TCR stimulation by immunogenic form of pathogen, either exogenous or endogenous, in combination with HLA to levels that surpass system's self-organized criticality, cause SLE.

P094 “Neonatal lupus”: a unique name for very different realities

Abstract Background Neonatal lupus is a rare condition linked to the maternal-fetal transmission of maternal anti-SSA and/or anti-SSB antibodies, more rarely anti-U1-RNP. The most frequent clinical manifestations are cardiac and cutaneous, more rarely hematological (thrombocytopenia, leuco-neutropenia), hepatic (cholestasis), neurological (spastic paresis, lymphocytic meningitis) or renal. We report two observations of neonatal lupus: a classic form, and a rare form. Observations First case: A female newborn, premature of 37 weeks, from a first-degree consanguineous marriage, having a mother followed for systemic lupus erythematosus, with poor therapeutic compliance, presented at H1 of life with neonatal respiratory distress. The clinical examination revealed severe bradycardia at 67 Bpm. The electrocardiogram showed complete atrioventricular block, with a moderate pericarditis on the echocardiography, minimal tricuspid insufficiency, interatrial communication, and a 6 mm foramen oval with LR shunt. The immunological test had objectified positive antinuclear, anti-SSA and anti-SSB antibodies. An implementation of a pacemaker with inter-atrial communication ligation were performed successfully. The evolution was marked by the appearance of a malar erythema with generalized lesions of discoid lupus at the age of 14 months, treated with local corticosteroid therapy, with good outcomes. The control immunological workup was negative at 18 months. Second case: A 2-month-old boy from a non-consanguineous marriage with a mother followed for Sjögren's syndrome was admitted for a symptomatology dating back to birth marked by the appearance of diffuse petechial purpura. Clinically, the infant presented diffuse discoid macules throughout the body. The somatic examination, particularly cardiovascular, was normal. The biological workup showed haemolytic anaemia with a positive coombs test and severe thrombocytopenia. The electrocardiogram and echocardiography were normal. The immunological workup had objectified positive anti-SSA, anti-SSB and anti-nuclear antibodies. The infant was treated by oral corticosteroids (prednisolone) for 4 months, with good outcomes. The control immunological workup was negative at 6 months. Conclusion The clinical manifestations of neonatal lupus are polymorphic, and the only one that may expose to life threat is complete atrioventricular block. All mothers with known lupus or with positive anti-SSA autoantibodies should be monitored during pregnancy with repeated ultrasounds.

Newly Generated DOCK8-Expressing T Follicular Helper Cells Cause Systemic Lupus Erythematosus

Pathogens including autoantigens all failed to induce systemic lupus erythematosus (SLE). We studied, instead of pathogen, the integrity of host’s immune response that recognized pathogen. By stimulating TCR with an antigen repeatedly to levels that surpass host’s steady-state response, self-organized criticality, SLE was induced in mice normally not prone to autoimmunity, wherein T follicular helper (Tfh) cells expressing guanine nucleotide exchange factor DOCK8 on the cell surface were newly generated. DOCK8+Tfh cells passed through TCR re-revision and induced varieties of autoantibody and lupus lesions. They existed in splenic red pulp and peripheral blood of active lupus patients, which subsequently declined after therapy. Autoantibodies and lupus lesions were healed by anti-DOCK8 antibody in the mice including (NZBxNZW)F1 and not raised in DOCK8-/- mice. Thus, DOCK8+Tfh cells, generated after repeated TCR stimulation by pathogen, either exogenous or endogenous, in combination with HLA to levels that surpass system’s self-organized criticality, cause SLE.

DOCK8-expressing Tfh cells cause SLE: autoimmunity via repeated TCR stimulation by antigen to levels that surpass system’s self-organized criticality

Abstract INTRODUCTION: The cause of autoimmunity remains unclear. Candidate pathogens including autoantigens all failed to induce, exist in, or heal upon their removal the prototypical autoimmune disease, systemic lupus erythematosus (SLE). We here investigated, instead of antigen, the immune response of host that recognized antigen. METHODS: We test the integrity of host’s immune response by stimulating TCR maximally to levels that surpass the limit of host’s steady-state immune response, self-organized criticality, by an antigen. RESULTS: After repeated stimulation by any immunogenic antigen, SLE was induced in mice normally not prone to autoimmune disease, wherein a novel T follicular helper (Tfh) cell type expressing the guanine nucleotide exchange factor DOCK8 on the cell surface was newly generated via resuscitation from antigen-induced anergy. DOCK8+ Tfh cells passed through TCR revision at the periphery, and induced a variety of autoantibodies and the lesion characteristic of SLE. They existed in splenic red pulp and in the circulation of active patients with SLE, which subsequently declined after conventional therapy. Lupus lesions of mice and the classical (NZBxNZW) F1 model mice were mostly cured by anti-DOCK8 antibody. CONCLUSION: Thus, disruption of host’s steady-state immune response by repeated TCR stimulation by immunogenic pathogen, either exogenous or endogenous, results in generation of DOCK8-expressing Tfh cells that cause autoantibodies and SLE.

Characterization of autoantibodies and cytokines related to cutaneous lupus erythematosus.

To investigate the profiles of anti-RPLP0, anti-galectin3 antibodies, interferon-α (IFN-α), interferon-λ1(IFN-λ1) and interleukin-17A/F(IL-17A/F) in the subtypes of cutaneous lupus erythematosus (CLE) including acute CLE (ACLE), subacute CLE (SCLE) and discoid lupus erythematosus (DLE). Serum levels of autoantibodies and cytokines were determined by enzyme-linked immunoabsorbent assay (ELISA). Lupus lesions were evaluated by cutaneous lupus erythematosus disease area and severity index (CLASI). Serum anti-RPLP0, anti-galectin3 antibodies and IFN-λ1 were higher in systemic lupus erythematosus (SLE) patients with skin lesions than those without skin lesions, compared to healthy controls. IFN-α, IL-17A and IL-17F was elevated in all patients regardless of skin lesions. The two antibodies, IFN-α and IL-17A were positively correlated with the CLASI score in all patients with CLE. In addition, serum IL-17A was positively correlated to the CLASI score of ACLE, SCLE and DLE, while anti-RPLP0 and anti-galectin3 antibodies were only correlated to the score of SCLE and IL-17F to DLE. Serum anti-RPLP0, anti-galectin3 antibodies, IFN-α, IFN-λ1 and IL-17A/F are associated with the occurrence of lupus skin lesions regardless of the systemic complications, whereas the profiles of these inflammatory mediators vary with the subtypes of lupus skin lesions.

Primary Nutritional Guidance at Systemic Lupus Erythematosus

Aims: To propose a primary nutritional recommendation for patients in the early stage of SLE to contribute to a better quality of life for those affected by the disease.
 Methodology: This is a theoretical study, with no direct approach or intervention to any patient. The research was carried out using a conceptual approach based on a narrative and explanatory literature review. The main key descriptors of health were: Lupus and skin lesions; butterfly wing or arthritis, nutrition and lupus. After that, a diet (with a menu) for primary nutritional guidance to patients with early symptoms was followed.
 Results: The scientific literature evaluates that Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune inflammatory disease, with no cure, which can have multiple causes (hormonal, infectious, genetic and environmental). The production of autoantibodies in tissues, generated from recognized apoptotic fragments, processed and associated with the Principal Human Histocompatibility Complex are also characteristic of SLE. In addition, SLE is mainly characterized by the involvement of the skin, joints, kidneys and serous membranes. The symptoms of SLE vary according to the stage of the disease, affecting different organs, tissues and, in more severe cases, the central and peripheral nervous system. The incidence of SLE is about ten times higher in females and affects more commonly Afro-American, Hispanic and Asian people. In addition, the individual's eating habits and nutritional status can influence the intensity and worsening of symptoms. Regarding nutritional guidance, it is of utmost importance to have anti-inflammatory and antioxidant substances in the diet, avoiding the exaggeration of bad fats, refined carbohydrates, and proteins.
 Conclusion: SLE patients should receive a multidisciplinary therapeutic approach, including follow-up by a nutritionist, who will prioritize the maintenance of the patient's adequate weight, avoiding overloading of his joints. This will contribute for a better quality of life for those affected.

TLR7/8 agonist accelerates lupus development with heart disease in lupus-prone mice

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by loss of self-tolerance to nuclear antigens leading to the production of pathogenic autoantibodies, immune complex deposition and multi-organ damage. Although the prevalence of heart disease is higher than 50% in SLE patients, its etiology remains unclear but both genetic and environment factors are likely involved. Here, we compared the effect of TLR7/8 agonist Resiquimod (R848) on lupus and cardiac lesion development in lupus-prone B6.Sle1.Sle2.Sle3 (TC) and congenic normal mice B6 mice. Two weeks of R848 treatment increased the production of antinuclear antibodies and induced antiphospholipid autoantibodies lined to vascular pathology in TC mice. Correspondently, R848 expanded the frequency of Tfh cells and plasma cells in TC mice as compared to R848 treated B6 mice. More importantly, unlike the near normal appearance in hearts of R848-treated B6 mice, R848 induced severe cardiac pathology in TC mice with infiltration of CD45+ cells, edema, hemorrhage, enlarged endothelial cells and myocyte damage. Our results indicate that heart disease develops by combining genetic predisposition to lupus together with TLR7/8 activation. This novel model may lead to the identification of autoimmune mechanisms responsible for lupus-associated heart disease.

Association between oral lesions and disease activity in lupus erythematosus

Mucosal involvement is frequently seen in cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). There is no consensus regarding the prevalence, and a wide range of lesions has been reported. Its prognostic significance is currently unknown and a matter of controversy. To classify oral lesions in lupus, evaluate their prevalence and assess their possible association with disease activity. We conducted a descriptive study between 2016 and 2017. A total of 150 lupus patients were matched by sex, age and smoking status with 151 healthy individuals. All subjects underwent a careful evaluation of oral mucosa. On the same day of the clinical assessment, each patient underwent a peripheral venous blood and urine analysis. All patients underwent a full medical history, physical examination and a careful examination of the oral cavity. For each one, we obtained photographs of ten areas of the oral cavity. Two dermatologists of our group blindly recorded the presence and morphology of oral lesions. The disease activity of CLE patients was scored using the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index, and in SLE patients, activity was measured using the Systemic Lupus Erythematosus Disease Activity Index. In CLE patients, there was a statistically significant correlation between higher cutaneous disease activity and the following oral findings: discoid plaques, cobblestone and red/brown-pigmented macules. In patients with CLE, red macules on jugal mucosa were statistically associated with anaemia and positive antinuclear antibodies titres; additionally, the presence of gingivitis was related to systemic inflammation. In SLE patients, gingival telangiectases were statistically significantly associated with leucopenia, hypocomplementemia and systemic inflammation. Biopsies on mucosal lesions were not performed. Some specific oral lesions correlate with disease activity in CLE and SLE.

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

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.

Nerve growth factor receptor expression marks activated human perivascular adventitial fibroblasts in distinct perturbed states

Abstract Vascular alterations are common in human autoimmune skin diseases, including systemic sclerosis and discoid lupus. Much is known about endothelial cell, pericyte and vascular smooth muscle cell activation. In contrast, the adventitial layer of the vascular unit is less well explored. This compartment serves as a reservoir for leukocytes and mesenchymal stem cells, and appears to play important sentinel and remodeling roles. We recently demonstrated that the compartment, as well as the perivascular adventitial fibroblasts, expand in the skin of systemic sclerosis, discoid lupus, and dermatitis patients. Vascular cell adhesion molecule-1 (VCAM) display marked activated adventitial fibroblasts in discoid lupus and dermatitis, and correlated with perivascular T cell infiltration. Here we demonstrate elevated expression of Nerve growth factor receptor (NGFR) by perivascular adventitial fibroblasts in the skin of systemic sclerosis patients but not control subjects. Adventitial NGFR expression occurred without elevated VCAM indicating a distinct activation state. Conversion to the NGFR+ state was also observed in the absence of large, perivascular leukocyte infiltrates. In systemic sclerosis, NGFR was more common than VCAM on perivascular adventitial fibroblasts. Conversely, in discoid lupus lesions, VCAM was more common than NGFR on adventitial fibroblasts suggesting two distinct activation programs. Similar adventitial NGFR staining was seen in both pathological (e.g. hypertrophic and keloid) and normal reparative skin wounds. Our data indicate that elevated NGFR expression can identify an activated perivascular adventitial fibroblast in disease.