Autoimmune Skin Disease Research Articles

Skin fragility in autoimmune blistering diseases of the skin

In many disorders, skin and/or mucosal changes are dominated by blisters, wounds, or erosions. While these changes can be observed during infective, traumatic, metabolic, or inflammatory processes, these are normally clinical hallmarks of the disruption of the cytoarchitectural stability of the skin. Several proteins, such as those located in the dermal-epidermal junction zone and forming the hemidesmosomes, or those forming epidermal desmosomes are crucial for the maintenance of skin integrity. Defective function may be genetically determined due to impaired or absent production of specific proteins (i.e., epidermolysis bullosa) or due to autoimmune disorders that lead to the production of autoreactive antibodies targeting desmosomal or hemidesmosomal skin antigens. The latter group of diseases are classically named autoimmune blistering diseases of the skin. These can be divided in the pemphigoid group, where antigens are components of the hemidesmosomes, and pemphigus group, where desmosomal proteins are targeted. In this review, we provide ashort vademecum of autoimmune skin disorders that are associated with skin fragility.

Phyto-pharmaceuticals as a safe and potential alternative in management of psoriasis: a review.

Psoriasis is a chronic autoimmune skin disease with a worldwide prevalence of 1-3 % results from uncontrolled proliferation of keratinocytes and affects millions of people. While there are various treatment options available, some of them may come with potential side effects and limitations. Recent research has shown that using bioactive compounds that originate from natural sources with a lower risk of side effects are relatively useful in safe management psoriasis. Bioactive compounds are molecules that are naturally available with potential therapeutic efficacy. Someof bioactive compounds that have shown promising results in the management of psoriasis include curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, etc., possess anti-inflammatory, antioxidant, immunomodulatory, and anti-proliferative properties, with capabilities to suppress overall pathogenesis of psoriasis. Moreover, these bioactive compounds are generally considered as safe andare well-tolerated, making them potential options for long-term use in the management of various conditions linked with psoriasis. In addition, these natural products may also offer a more holistic approach to treat the disease, which is appealing to many patients. This review explores the bioactive compounds in mitigation of psoriasis either innative or incorporated within novel drug delivery. Moreover, recent clinical findings in relation to natural product usage have been also explored.

COVID-19 as a Risk Factor For Autoimmune Skin Disease

COVID-19 as a Risk Factor For Autoimmune Skin Disease

ROLE OF INNATE IMMUNE RECEPTORS IN THE PSORIASIS DEVELOPMENT

Psoriasis is an immune-mediated autoimmune inflammatory skin disease with a prevalence of 2 to 3% worldwide. In the psoriasis development and pathogenesis an important role is played by disorders in the immune system. Disruption of the innate and adaptive immune response mechanisms with the involvement of keratinocytes leads to the initiation and maintenance of inflammation. Immune reactions are activated in the skin, in which various cells participate (macrophages, dendritic cells, mast cells, innate immune lymphoid cells, melanocytes, keratinocytes, Langerhans cells and γδT cells; T and B cells; epithelial endothelial and stromal cells of the skin), each of which expresses pattern recognition receptors that respond to pathogens and cell damage itself. Many of these receptors, in particular Toll-like receptors and NOD-like receptors play an important role in the pathogenesis of psoriasis. The associated innate receptors signaling cascades that activate in the skin cells may become potential targets for the treatment of this disease. To date, there are several approved drugs for biological therapy of psoriasis. The study of the role of the innate immune cells receptors in inflammatory skin pathologies requires further exploration and new developments.

Analysis of vitamin D metabolism, thyroid and autoimmune markers in the vitiligo pathways and their possible interaction with sleep.

Vitiligo is an autoimmune skin disease that can be influenced by stress, including that resulting from sleep deprivation and sleep disturbances. Sleep is essential in the regulation of several hormonal, metabolic and autoimmune pathways that may have important roles in vitiligo. This study aimed to investigate the potential interplay between hormonal, metabolic, and autoimmune markers in vitiligo patients, and the possible influence of sleep quality in these vitiligo pathways. A cohort of 30 vitiligo patients and 26 healthy controls were assessed for various laboratory markers, including thyroid-stimulating hormone (TSH), parathyroid hormone (PTH), serum calcium, 1.25(OH)2D, 25(OH)D, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and antinuclear antibodies (ANA). The study evaluated sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Positive anti-TPO were found in the vitiligo group, but did not in the control group. Vitamin D 25(OH)D mean levels were clinically insufficient in both groups (< 30mg/dL). Reactive ANA was analyzed with 2 variables related to vitiligo: phototherapy and skin activity. No statistical correlation was found in the chi-square test on this relationship. Descriptive findings have shown that the positivity to anti-TPO and anti-TG, associated or not with reactive ANA, was higher in vitiligo group. Great part (85.7%) of vitiligo group were "poor sleepers" (PSQI > 5), which has increased (88.2%) when considering only individuals with signs of vitiligo activity. Autoimmune hypothyroidism and positive anti-TPO are expected in vitiligo, although this marker is not usually measured in the first laboratory screening to this disease. Adequate vitamin D levels may be a key adjuvant in skin pigmentation, and be related to sleep quality and immune regulation, as this vitamin can be related to better sleep and immunomodulation in autoimmune diseases. Evaluating ANA before phototherapy can be controversial, but it should be considered in cases with a poor response to this treatment, or when there is a higher risk of other autoimmune diseases. Poor sleep predominated in the vitiligo group, based on PSQI scores that reported worse subjective sleep in these patients. Worse sleep predominated in individuals with signs of skin activity and reactive autoimmune markers. Screening these components could be important in the management of vitiligo, as maintaining body homeostasis can help to improve the disease course. Sleep should be considered as a potential modulator of several multidirectional vitiligo pathways.

Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients of Bullous Pemphigoid with or without Parkinson's Disease.

High positivity rate of skin phosphorylated α-synuclein (P-SYN) was observed in Parkinson's disease (PD). Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases associated with PD. Our aim was to investigate whether BP patients might be a targeted risk population for the screening of skin P-SYN. Skin P-SYN expression was evaluated by immunohistochemistry in BP patients with/without PD. Twenty-two BP patients with PD, 24 BP patients without PD, and seven healthy donors were enrolled. Colocalization of P-SYN and PGP9.5 was found in all BP patients, but only one healthy control, whereas BP patients with PD showed higher expression than BP patients without PD (mean ± standard deviation, 10.7 ± 6.7 vs. 7.3 ± 3.2; P = 0.027). Positive expression was mainly observed in basement membrane zone and dermis. These results indicated BP patients might be a targeted risk population for the screening of skin P-SYN, which was helpful for the detection of PD early. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

HDAC1-mediated regulation of KDM1A in pemphigus vulgaris: unlocking mechanisms on ERK pathway activation and cohesion loss.

Pemphigus vulgaris (PV) is an autoimmune skin disorder characterized by the loss of cell cohesion, with the histone deacetylase 1 (HDAC1) and lysine demethylase 1A (KDM1A) playing critical roles in its pathogenesis. This study aimed to elucidate the molecular mechanisms behind PV, focusing on the function of HDAC1 and KDM1A in disease onset and progression. Based on in vitro and in vivo PV models, we observed a significant increase in HDAC1 mRNA and protein levels in skin tissues of PV patients. Inhibition of HDAC1 ameliorated cell damage and reduced the loss of cell cohesion in human epidermal keratinocytes (HEKs) induced by PV-IgG. Our findings suggest that HDAC1 regulates KDM1A expression through deacetylation, with a notable deficiency in KDM1A expression in PV. Overexpression of KDM1A mitigated cell damage and cohesion loss. The extracellular signal-regulated kinase (ERK) pathway serves as a downstream executor of the HDAC1/KDM1A axis. Inhibiting HDAC1 and increasing KDM1A expression suppressed ERK phosphorylation, reducing PV-related apoptosis. These insights provide a new perspective on treating PV, highlighting the therapeutic potential of targeting HDAC1 expression. The regulatory mechanism of the HDAC1/KDM1A/ERK axis offers crucial clues for understanding PV pathogenesis and developing novel treatments.

The association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study.

Bullous pemphigoid (BP) is an autoimmune skin disease that affects mainly older people. Numerous drugs have been previously associated with BP based on case series and small hospital-based studies. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of potential increased risk of BP following certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different types of culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved well-being. To determine the association between drugs/vaccines commonly prescribed to older people and BP risk. We conducted a population-based nested case-control study between 1998-2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched BP cases with up to 5 controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, we considered prescriptions may be prescribed for undiagnosed symptoms of BP which resemble skin infection (protopathic bias) in a sensitivity analysis. Antibiotics were the therapeutic group associated with the highest risk of BP (OR: 4.60; 95%CI 4.40-4.80). However, after adjusting for protopathic bias, the OR reduced to 2.08 (95%CI 1.99-2.17). After adjusting for protopathic bias, of all antibiotic classes and subclasses, penicillins and penicillinase-resistant penicillins had the strongest associations with BP risk (OR: 3.44; 95%CI 3.29-3.60; sensitivity analysis OR; 1.74; 1.66-1.84 and OR: 7.56; 95%CI 7.15-8.00; sensitivity analysis OR: 2.64; 95%CI 2.45-2.85, respectively). Other drugs strongly associated with increased risk were gliptins (OR: 2.77; 95% CI 2.37-3.23), and second-generation antipsychotics (OR: 2.58; 95%CI 2.20-3.03). Healthcare professionals need to be aware of BP risk in older people particularly when prescribing penicillinase-resistant penicillins, gliptins, and second-generation antipsychotic drugs to recognise and manage BP early. Due to the low prevalence of disease, we do not suggest avoidance of drugs/vaccines to prevent BP. Further research should consider recency, dosage, and duration of antibiotic treatments.

Eugenol-Loaded Lipid Nanoparticles-Derived Hydrogels Ameliorate Psoriasis-like Skin Lesions by Lowering Oxidative Stress and Modulating Inflammation.

Psoriasis is a chronic T-cell-mediated autoimmune skin disorder characterized by excessive epidermal thickening, overproliferation of keratinocyte, disruption of epidermal cell differentiation, and increased blood vessel growth in the dermal layer. Despite the common use of corticosteroids in psoriasis treatment, their limited efficacy and numerous side effects pose significant challenges. This research introduces a promising alternative approach by encapsulating eugenol (EU) in soya phosphatidylcholine (SPC) nanoparticles (EUNPs) which showed spherical shape nanoparticles with a hydrodynamic size of approximately 200 nm, polydispersity index 0.23, encapsulation efficiency of 85% having good colloidal stability indicated by ζ-potential of -27 mV. Later on, these EUNPs were formulated into a topical hydrogel system by using Carbopol 974P (EUNPGel), which exhibited superior drug loading, enhanced release kinetics for 48 h, long-term stability, and the ability to scavenge reactive oxygen species (ROS). Furthermore, EUNPs inhibited keratinocyte proliferation, induced apoptosis, and augmented the uptake of IL-6-mediated inflammation in human keratinocyte cells. Application of EUNPs-loaded gels (EUNPGel) to imiquimod-induced psoriatic lesions demonstrated effective dermal penetration, suppressed keratinocyte hyperplasia and restored epidermal growth. This led to a remarkable reduction in the Psoriasis Area and Severity Index (PASI) score from 3.75 to 0.5 within 5 days. This novel approach enhances ROS scavenging capacity, improves cellular uptake, facilitates skin penetration and retention, reduces the activity of hyperactive immune cells, and suggests potential applications for treating other immune-related disorders such as acne and atopic dermatitis.

A unique approach for investigating skin lesions and their relationship with TCM syndrome differentiation in alopecia areata

Background: Alopecia areata is also known as ‘oil wind’ in Chinese medicine. Alopecia areata is a debilitating autoimmune skindisease characterized by patches of non-scarring hair loss and inflammation that damages the scalp and body hair in a variable,often relapsing or permanent fashion. It is not quite obvious how the various Traditional Chinese Medicine (TCM) syndromes differentiate between the skin lesions under dermatoscopy caused by alopecia areata. Objective: This study aimed to provide a rational basis for TCM syndrome differentiation of alopecia areata and investigate the role of skin lesions in various TCM syndromes of alopecia areata under dermatoscopy. Methods: The dermatologist used a dermatoscope to take four images of the patient's skin lesion area and the skin lesion junction. Two of the images were captured with polarized light, while the other two were taken with non-polarized light. Patients with alopecia areata who had TCM syndrome differentiation were identified and examined using dermatoscopy. The occurrence of the yellow dot, white dot, exclamation mark hair and vascular sign, was determined and then statistically analyzed. Results: The positive rates of vascular signs relate to alopecia areata, exclamation mark hair relates to Qi-blood deficiency and white dot corresponded to liver and kidney deficiency. All the positive rates were statistically significant (P &lt; 0.05). Compared to vascular sign, white dot sign, and Qi-blood deficiency syndrome groups, the positive rate of yellow dot syndrome was not significant (P&gt;0.05) Conclusion: The findings suggest that particular skin lesions contribute to differentiating different TCM syndromes associated with alopecia areata. Skin lesions examined under dermatoscopy can assist in diagnosing the TCM syndromes associated with alopecia areata. Keywords: Dermatoscopic signs; Alopecia areata; TCM syndromes; Qi and blood deficiency; Liver and kidney deficiency.

An overview of bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune bullous skin disease that causes blistering due to the presence of immunoglobulin G antibody/antigen complexes at the dermal-epidermal junction. Primarily seen in people over the age of 60, BP can be triggered by medications, infections, comorbidities, and environmental skin stressors. The clinical presentation of BP begins with non-bullous patches that may resemble eczema or urticaria; this stage is followed by the development of tense vesiculobullous lesions in flexural areas that usually heal without scarring. Erosions sometimes develop on mucous membranes such as the oral cavity or genitalia. The diagnosis is made by using direct immunofluorescence on punch biopsy samples taken from perilesional skin, which will show the linear deposits of immunoglobulin G antibody/antigen complexes along the dermal-epidermal junction. Salt-split skin testing can also confirm the direct immunofluorescence results. Treatment options include the removal of any triggering factors and the use of topical or oral corticosteroids. If prolonged treatment is required, steroid-sparing medications such as immunosuppressants, immunoglobulins, monoclonal antibody agents, or doxycycline can be combined to achieve satisfactory results. BP causes an increased risk of developing pulmonary emboli or stroke, but most patients will be able to achieve remission after 6–60 months of treatment without further complications.

Immune-Molecular Link between Thyroid and Skin Autoimmune Diseases: A Narrative Review.

Autoimmune skin disorders, including Psoriasis, Lichen Planus, Vitiligo, Atopic Dermatitis, and Alopecia Areata, arise from a combination of genetic predisposition, external factors, and immunological dysfunction. It is well-documented that there is a strong correlation between autoimmune thyroid diseases and a range of dermatological disorders, especially urticaria. This review investigates possible links between autoimmune thyroiditis and a broader spectrum of autoimmune skin conditions, analyzing shared genetic markers, immunological mechanisms, and clinical correlations. Common pathogenic mechanisms include disrupted immune tolerance and oxidative stress, leading to chronic inflammation. Genetic factors, such as IL-23 receptor gene variants, increase the risk for Psoriasis, Alopecia Areata, and Hashimoto's thyroiditis. Additionally, CTLA-4 mutations enhance susceptibility to autoimmune thyroid and skin disorders. Shared genetic susceptibility was also reported in Lichen Planus and Vitilgo, even if different genetic loci might be involved. The breakdown of the immune system can determine a pro-inflammatory state, facilitating the development of autoimmunity and auto-antibody cross-reactions. The presence of similar antigens in skin cells and thyrocytes might explain why both tissues are affected. The significant overlap between these conditions emphasizes the necessity for a comprehensive diagnosis workup and treatment. Future research should focus on clarifying specific immunological pathways and identifying novel biomarkers.

Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus

Cell-cell junctions, and specifically desmosomes, are crucial for robust intercellular adhesion. Desmosomal function is compromised in the autoimmune blistering skin disease pemphigus vulgaris. We combine whole-genome knockout screening and a promotor screen of the desmosomal gene desmoglein 3 in human keratinocytes to identify novel regulators of intercellular adhesion. Kruppel-like-factor 5 (KLF5) directly binds to the desmoglein 3 regulatory region and promotes adhesion. Reduced levels of KLF5 in patient tissue indicate a role in pemphigus vulgaris. Autoantibody fractions from patients impair intercellular adhesion and reduce KLF5 levels in in vitro and in vivo disease models. These effects were dependent on increased activity of histone deacetylase 3, leading to transcriptional repression of KLF5. Inhibiting histone deacetylase 3 increases KLF5 levels and protects against the deleterious effects of autoantibodies in murine and human pemphigus vulgaris models. Together, KLF5 and histone deacetylase 3 are regulators of desmoglein 3 gene expression and intercellular adhesion and represent potential therapeutic targets in pemphigus vulgaris.

Monoclonal antibodies for inflammatory, autoimmune and oncological skin diseases

In 1997 rituximab, agenetically engineered chimeric monoclonal antibody (mAb) targeting CD20 expressed on Bcells was approved for treatment of non-Hodgkin's lymphoma. Since then, pharmacological improvements combined with increased knowledge on the immunopathogenesis of diseases led to the development of specific mAb targeting different antigens (e.g., interleukins or transmembrane receptors). This approach reshaped the therapeutic methodology in many fields, including dermatology. Nowadays, the treatment of frequent and possibly impairing inflammatory disorders such as psoriasis, atopic dermatitis or hidradenitis suppurativa have different mAbs approved for both adult and pediatric patients. This class of drugs often shows amore favorable outcome and abetter safety profile than routine immunosuppressants, such as steroids and steroid-sparing substances. For many years mAbs also represented apillar of oncological treatment for severe diseases such as malignant melanoma or Merkel cell carcinoma. This review summarizes the current knowledge on already approved and promising new mAbs for the treatment of inflammatory and oncological skin diseases.

Long-Term Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: Follow-Up Data from a 3-Year Open-Label Extension Study

BackgroundDermatomyositis (DM) is a rare autoimmune condition involving skin manifestations often resistant to standard treatments like immunosuppressants and antimalarials. Biopsies show elevated inflammatory cells such as CD4+ T cells, dendritic cells, and cytokines. Lenabasum, a selective CB2 agonist, has demonstrated significant benefits in treating autoimmune skin diseases. ObjectivesThis study utilizes data from the open-label extension (OLE) phase of the lenabasum phase 2 trial and additional post-OLE follow-up data. Key aims include evaluating the drug's long-term effectiveness and assessing disease manifestation recurrence. MethodsThe phase 2 lenabasum trial enrolled patients with treatment-resistant, skin-predominant DM. The OLE consisted of a 3-year period during which 20 patients were on the drug for the entire duration, with assessments every 8 weeks to evaluate drug safety and efficacy. Subsequently, a follow-up retrospective chart review was performed on patients who completed the OLE, as well as on control subjects with DM who did not participate in the lenabasum trial. ResultsBy week 68, patients exhibited reductions in CDASI activity score (-21.8), Patient Skin Activity VAS (-3.0), and Skindex-29 (-28.0) from OLE baseline. Post-OLE, 58.3% maintained stable disease, significantly higher than controls (p=0.035), with 41.7% not experiencing flares compared to 91.6% of controls. Additionally, 50% of patients reported sustained pruritus improvement. ConclusionsData from OLE and subsequent follow-up periods demonstrate lenabasum's efficacy in maintaining disease stability, reducing flares, and improving DM symptoms, suggesting it is a promising option for treatment-resistant skin-predominant DM patients.

The causal effects of inflammatory and autoimmune skin diseases on thyroid diseases: evidence from Mendelian randomization study.

To clarify the controversy between inflammatory or autoimmune skin diseases and thyroid diseases, we performed two-sample Mendelian randomization (MR) analyses. Genetic data on factors associated with atopic dermatitis (AD, n=40,835), seborrheic dermatitis (SD, n=339,277), acne (n=363,927), rosacea (n=299,421), urticaria (n=374,758), psoriasis (n=373,338), psoriasis vulgaris (n=369,830), systemic lupus erythematosus (SLE, n=14,267), vitiligo (n=353,348), alopecia areata (AA, n=361,822), pemphigus (n=375,929), bullous pemphigoid (BP, n=376,274), systemic sclerosis (SSc, n=376,864), localized scleroderma (LS, n=353,449), hypothyroidism (n=314,995 or n=337,159), and hyperthyroidism (n=281,683 or n=337,159) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates of inflammatory or autoimmune skin diseases on the risk of thyroid diseases, complemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). AD, SLE, SD, and psoriasis vulgaris were associated with an increased risk of hypothyroidism, whereas BP was associated with a lower risk of hypothyroidism (all with p < 0.05). The multivariable MR analyses showed that AD (OR = 1.053; 95%CI: 1.015-1.092; p = 0.006), SLE (OR = 1.093; 95%CI: 1.059-1.127; p < 0.001), and SD (OR = 1.006; 95%CI: 1.002-1.010; p = 0.006) independently and predominately contributed to the genetic causal effect on hypothyroidism after adjusting for smoking. The results showed no causal effects of inflammatory or autoimmune skin diseases on hyperthyroidism. The findings showed a causal effect of AD, SLE, SD on hypothyroidism, but further investigations should be conducted to explore the pathogenic mechanisms underlying these relationships.

New Insights in Psoriasis Management using Herbal Drug Nanocarriers.

Psoriasis (Pso) is an autoimmune inflammatory skin disease characterized by red plaques covered in silver scales. The existing treatments provide limited benefits and are associated with certain drawbacks which limit their use. Thus, there is a need to explore more options that are highly target-specific and associated with minimal side effects. Researchers have thoroughly investigated the use of herbal drugs for their therapeutic potential. Preclinical studies demonstrate that phytochemicals such as curcumin, psoralen, and dithranol have antipsoriatic effects. These phytoconstituents inhibit the signalling pathways, such as the interleukin (IL) 23/Th17 axis and IL-36 inflammatory loop involved in the pathogenesis of Pso. These phytoconstituents down-regulate the pro-inflammatory cytokines like IL-17 and tumor necrosis factor (TNF)-α. However, their application in clinical settings is limited due to poor bioavailability and access to target sites. Combining phytoconstituents with modern delivery platforms like nanocarriers can address these shortcomings and improve therapeutic efficacy. This review explores the potential of herbal remedies as a substitute for conventional therapies, emphasizing the clinical trials conducted with these herbal medicines. The paper is supported by the discussion on nanocarriers like liposomes, niosomes, emulsomes, ethosomes, nanostructured lipid carriers, nanoemulsions, and dendrimers that are used to deliver herbal medicines.

Role of serum cd4+, cd25+, and foxp3+ cells’ segmental and nonsegmental vitiligo

Background Vitiligo is an autoimmune skin disease presented with depigmented macules and patches. Vitiligo has an impact on the quality of life. The etiopathogenesis of vitiligo is multifactorial, including genetic, immune dysregulation, and oxidative stress mechanisms. Lately, several researches have underlined the pivotal function of regulatory T cells (Tregs) in the vitiligo pathogenesis with lack of data regarding their role in segmental vitiligo (SV). Objective To investigate the role of Tregs in SV and nonsegmental vitiligo (NSV) pathogenesis and its correlation with disease activity and severity. Patients and methods This case–control study included 20 cases with NSV and 10 cases with SV in addition to 10 healthy volunteers. Vitiligo Area Scoring Index and Vitiligo Disease Activity scores were estimated for vitiligo cases and all the included participants were assessed for the percentage of serum CD4+, CD25+, and FOXP3+ T cells using flow cytometry staining buffer. Results There was significant reduction of the peripheral Tregs in NSV cases in comparison with healthy participants and negative correlation with their percentage to disease activity. On the other hand, there was insignificant difference between the percentage of peripheral Tregs in SV cases and healthy participants. Also, there was insignificant correlation between peripheral Tregs and both severity and activity of the disease among SV cases. Conclusion NSV cases showed significant reduction of the peripheral Tregs and negative correlation with disease activity, indicating the importance of Tregs in the etiopathogenesis of NSV and hence future targeting therapy. On the other hand, in SV cases, there was insignificant reduction of peripheral Tregs and insignificant correlation between their percentage and both severity and activity indicating mosaic etiopathogenesis.

Abstract P184: Increased Granulopoiesis, Kidney Neutrophil Infiltration, and Renal Damage in a Mouse Model of Psoriasis

Psoriasis is an autoimmune skin disease marked by T cell-mediated hyperproliferation of epidermal keratinocytes. Most psoriasis-related morbidity and mortality stems from an elevated risk of renal and cardiovascular disease, but mechanisms remain unclear. Although neutrophils are not directly targeted with current psoriasis therapies, neutrophils are increased in the skin and circulation of these patients. We hypothesized that excess skin inflammation in psoriasis drives increased G-CSF-dependent granulopoiesis leading to renal neutrophil infiltration and dysfunction. Employing a KC-Tie2 mouse model of psoriasis with keratinocyte-specific overexpression of the angiopoietin receptor Tie2 (KC-Tie2), we observed 2-3-fold elevations in multiple indices of renal damage including urine albumin, urine NGAL, and glomerulosclerosis in KC-Tie2 mice compared to littermate controls (all P&lt;0.05). KC-Tie2 mice also demonstrated 13 mm Hg higher daytime systolic blood pressure compared to littermate controls (P&lt;0.05). Using flow cytometry, we found that KC-Tie2 mice had an increase not only in cutaneous neutrophils but also an approximate 10-fold increase in renal neutrophils (P&lt;0.001). KC-Tie2 kidneys also exhibited increased vital and suicidal neutrophil extracellular trap (NET) formation, representing a potential mechanism for the observed renal damage. Interestingly, the increase in renal neutrophils was selective relative to other major immune cell populations such as dendritic cells, lymphocytes, monocytes, and macrophages. Similar selective increases in neutrophils were noted in the circulation, aorta, and spleen. We thus examined neutrophil production in the bone marrow, and observed significant increases in immature Ly6g low and Ly6g intermediate neutrophils (P&lt;0.0001) as well as total Ly6g + neutrophils (P&lt;0.05), with no change in mature Ly6g high neutrophils in the bone marrow of KC-Tie2 mice. These findings are consistent with increased granulopoiesis, prompting an examination of the key mediator of granulopoiesis, granulocyte colony-stimulating factor (G-CSF). KC-Tie2 mice exhibited marked increases in G-CSF in both the skin and plasma (P&lt;.001 for both). In conclusion, our findings demonstrate increased renal damage in a mouse model of psoriasis, concomitant with increases in granulopoiesis and total and NETotic renal neutrophils, potentially unveiling a novel link between skin inflammation and renal damage via enhanced G-CSF-mediated granulopoiesis.

Stem-cell therapy in dermatology – Challenges and opportunities

The remarkable characteristics of stem cells (SCs), particularly their potency, capacity for self-renewal, and clonality, are well known. In recent years, there have been notable advancements in the field of cell therapy. Due to its distinctive qualities and versatility, this innovative therapy is already turning into a potentially helpful remedy for several diseases. Numerous dermatological problems, including autoimmune skin disorders, atopic dermatitis, skin aging, wound healing, scar repair, and many more, have been treated with SC-based therapies. Their application in regenerative medicine and esthetic dermatology is based on their capacity to self-renew and differentiate into distinct cell types. Given their abundance and relative simplicity of collecting adipose-derived SCs have shown to be particularly appealing in terms of appearance. SC therapy has demonstrated encouraging results in both skin regeneration and androgenetic alopecia treatment. Despite favorable preclinical evidence and clinical investigations, further randomized, controlled trials and treatment standardization are required to fully comprehend the role of SCs in the treatment of dermatological conditions, especially esthetics. The purpose of this article is to provide a general review of cell-based therapy, including its current uses, limits, and future possibilities in the field of dermatology.