Skin Biopsy Research Articles

Cytokines and chemokines skin gene expression in correlation with immune cells in blood and severity in equine insect bite hypersensitivity

BackgroundInsect bite hypersensitivity (IBH) is the most frequent skin allergy of horses and is highly debilitating, especially in the chronic phase. IBH is caused by IgE-mediated hypersensitivity reactions to culicoides midge bites and an imbalanced immune response that reduces the welfare of affected horses.ObjectiveIn the present study, we investigated the pathological mechanisms of IBH, aiming to understand the immune cell modulation in acute allergic skin lesions of IBH horses with the goal of finding possible biomarkers for a diagnostic approach to monitor treatment success.MethodsBy qPCR, we quantified the gene expression of cytokines, chemokines, and immune receptors in skin punch biopsies of IBH with different severity levels and healthy horses simultaneously in tandem with the analysis of immune cell counts in the blood.ResultsOur data show an increase in blood eosinophils, monocytes, and basophils with a concomitant, significant increase in associated cytokine, chemokine, and immune cell receptor mRNA expression levels in the lesional skin of IBH horses. Moreover, IL-5Ra, CCR5, IFN-γ, and IL-31Ra were strongly associated with IBH severity, while IL-31 and IL-33 were rather associated with a milder form of IBH. In addition, our data show a strong correlation of basophil cell count in blood with IL-31Ra, IL-5, IL-5Ra, IFN-γ, HRH2, HRH4, CCR3, CCR5, IL-12b, IL-10, IL-1β, and CCL26 mRNA expression in skin punch biopsies of IBH horses.ConclusionIn summary, several cytokines and chemokines have been found to be associated with disease severity, hence contributing to IBH pathology. These molecules can be used as potential biomarkers to monitor the onset and progression of the disease or even to evaluate and monitor the efficacy of new therapeutic treatments for IBH skin allergy. To our knowledge, this is the first study that investigated immune cells together with a large set of genes related to their biological function, including correlation to disease severity, in a large cohort of healthy and IBH horses.

Senomorphic activity of a combination of niacinamide and hyaluronic acid: correlation with clinical improvement of skin aging

Intrinsic and extrinsic factors, including lifestyle and sun exposure, can contribute to cell senescence, which impairs skin homeostasis, that may in turn lead to skin aging. Senescent cells have a specific secretome, called the senescence-associated secretory phenotype (SASP) that includes MMPs, CXCLs and S100A8/9. Reducing the SASP with senotherapeutics is a promising strategy to reduce skin aging. Here we evaluated the effect of a formula containing niacinamide and hyaluronic acid, which are known to limit senescence and skin aging. We conducted three different studies. (1) Ex vivo explants treated with the formula had more collagen and glycosaminoglycan. (2) In a clinical trial with forty-four women, two months of treatment improved fine lines, wrinkles, luminosity, smoothness, homogeneity, and plumpness. (3) In a third study on thirty women, we treated one arm for two months and took skin biopsies to study gene expression. 101 mRNAs and 13 miRNAs were differentially expressed. We observed a likely senomorphic effect, as there was a decrease in many SASP genes including MMP12 and CXCL9 and a significant downregulation of autocrine signaling genes: S100A8 and S100A9. These pharmaco-clinical results are the first to demonstrate the senomorphic properties of an effective anti-aging formula in skin.

ACKR1+ Endothelial Cells Mediate Leukocyte Infiltration and Synergize with SFRP2/ASPN+ Fibroblasts to Promote Skin Fibrosis in Systemic Sclerosis.

Skin fibrosis is the most typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS) with unclear etiology and few effective treatments. Though excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, many lines of evidence suggested that vascular damage was the initiating event and various cell types along with fibroblasts worked together to contribute to the pathogenesis of skin fibrosis. We sought to explore the relationships between vascular endothelial cell lesions and immune cell infiltration, along with the cell-cell interactions among various cell types within the fibrotic skin ecosystem. Single-cell RNA-seq (10x Genomics) was performed on skin biopsies of 3 healthy donors and 7 SSc patients in Chinese. The additional 3 localized scleroderma patients' data from NCBI database (GSE160536) were integrated by Harmony. CellChat package (v1.5.0) was applied to analyze cell communication network. Transwell assay and subcutaneous bleomycin (BLM) injection in mice were used to explore the role of ACKR1 on immune cell infiltration. Milo single-cell western blot was applied to show the activation of fibroblast subclusters. A total of 62,295 cells were obtained and subpopulations of stromal and immune cells were identified. Interaction network analysis revealed that multiple chemokines secreted by macrophages, pericytes, and pro-inflammatory fibroblasts could bind with Duffy antigen/receptor for chemokines (ACKR1), which is highly expressed on ACKR1+ endothelial cells of lesion skin. Transwell assay revealed that over-expressed ACKR1 in HUVEC facilitated leukocyte infiltration under the treatment of IL8. The BLM mice showed enhanced ACKR1 expression, massive immune cell infiltration, and fibrosis in skin, which could be attenuated by ACKR1 inhibition. Furthermore, infiltrated macrophages with TGFB1 or PDGFB high production could activate SFRP2/ASPN+ fibroblasts to contribute to excessive accumulation of extracellular matrix (ECM), and the SOX4-ASPN axis plays an important role in the TGF-β signaling cascade and the etiology of skin fibrosis. Our results reveal that highly expressed ACKR1 in endothelial cells of fibrotic skin tissue promotes immune cell infiltration, and SFRP2/ASPN+ fibroblasts synergize to exacerbate skin fibrosis.

A biopsy-sized 3D skin model with a perifollicular vascular plexus enables studying immune cell trafficking in the skin

Human skin vasculature features a unique anatomy in close proximity to the skin appendages and acts as a gatekeeper for constitutive lymphocyte trafficking to the skin. Approximating such structural complexity and functionality in 3D skin models is an outstanding tissue engineering challenge. In this study, we leverage the capabilities of the digital-light-processing bioprinting to generate an anatomically-relevant and miniaturized 3D skin-on-a-chip (3D-SoC) model in the size of a 6 mm punch biopsy. The 3D-SoC contains a perfusable vascular network resembling the superficial vascular plexus of the skin and closely surrounding bioengineered hair follicles. The perfusion capabilities of the 3D-SoC enables the circulation of immune cells, and high-resolution imaging of the immune cell-endothelial cell interactions, namely tethering, rolling, and extravasation in real-time. Moreover, the vascular pattern in 3D-SoC captures the physiological range of shear rates found in cutaneous blood vessels and allows for studying the effect of shear rate on T cell trafficking. In 3D-SoC, as expected, in vitro-polarized T helper 1 (Th1) cells show a stronger attachment on the vasculature compared to naïve T cells. Both naïve and T cells exhibit higher retention in the low-shear zones in the early stages (<5 min) of T cell attachment. Interestingly, at later stages T cell retention rate becomes independent of the shear rate. The attached Th1 cells further transmigrate from the vessel walls to the extracellular space and migrate toward the bioengineered hair follicles and interfollicular epidermis. When the epidermis is not present, Th1 cell migration toward the epidermis is significantly hindered, underscoring the role of epidermal signals on T cell infiltration. Our data validates the capabilities of 3D-SoC model to study the interactions between immune cells and skin vasculature in the context of epidermal signals. The biopsy-sized 3D-SoC model in this study represents a new level of anatomical and cellular complexity, and brings us a step closer to generating a truly functional human skin with its tissue-specific vasculature and appendages in the presence of circulating immune cells.

Psoriasis in pediatric dermatological clinical practice: diagnosis and management

The relevance of this topic is confirmed by the widespread psoriasis prevalence. Psoriasis in children has severe forms growth and diagnostic difficulties. It is crucially important to examine histologically the skin especially in pediatric dermatological clinical practice. According to our observations Pityriasis Rubra Pilaris has become one of the most frequent dermatoses with which differential diagnosis of psoriasis has to be carried out. A clinical dermatosis observation in a 13-year-old girl is described. The disease was similar to the manifestations of Pityriasis Rubra Pilaris. The results of the affected skin biopsy study did not exclude this diagnosis. The clinical and morphological manifestations of the dermatosis could be effected by steroid therapy. Subsequent dynamic observation and histological examination allowed us to diagnose psoriasis. Current data is collected and presented. The choice of external therapy in pediatric practice is a controversial topic. Clinical results of the Activated Zinc Pyrithion external forms use in the psoriasis treatment are presented.

Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations. We recruited 50 SLE patients (1 male to 12.5 females, aged 20-80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin. Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (p = .0143); furthermore, they were more likely to have a history of hypocomplementemia (p = .0058) and to be treated with cyclosporine A (p = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN. This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.

Diagnostic Utility of Multiplex Polymerase Chain Reaction in Patients of Clinically Suspected Pure Neuritic Leprosy by Identifying Mycobacterium leprae in Skin Biopsy Samples and Nasal Swabs.

Pure neuritic leprosy (PNL) often remains underdiagnosed due to the lack of simple, reliable diagnostic tools to detect Mycobacterium leprae. This study aimed to investigate the utility of multiplex polymerase chain reaction (MPCR) in easily accessible and less invasive biopsy sites, including skin biopsy samples and nasal swabs (NSs), to detect M. leprae. A total of 30 (N = 30) clinically suspected and untreated patients with PNL were recruited. Nasal swabs and skin biopsy samples from the innervation territory of an "enlarged nerve" were collected. DNA was extracted and subjected to MPCR (targeting leprae-specific repetitive element [RLEP], 16S rRNA, and SodA genes) and RLEP-PCR (individual gene PCR). The PCR products were analyzed by 3% agarose gel electrophoresis. In 30 patients with clinically suspected PNL, 60% (N = 18) of skin biopsy samples and 53% (N = 16) of NSs were found positive for M. leprae DNA by MPCR, whereas only 23.3% (N = 7) of skin biopsy samples and 10% (N = 3) of NSs were found positive by RLEP-PCR. MPCR demonstrated a greater positivity rate than did RLEP-PCR for detection of M. leprae. Serologic positivity for anti-natural disaccharide-octyl conjugated with bovine serum albumin (ND-O-BSA) antibodies was 80% (16/20), including 35% (7/20) of PNL patients for which the skin MPCR was negative. Both serologic positivity and skin MPCR positivity were observed in 65% of patients (N = 20). Multiplex polymerase chain reaction is a useful tool for detection for M. leprae in skin biopsy samples and NSs in clinically suspected cases of PNL, with the added advantages of being less invasive and technically easier than nerve biopsy.

Diagnostic Utility of Multiplex Polymerase Chain Reaction in Patients of Clinically Suspected Pure Neuritic Leprosy by Identifying Mycobacterium leprae in Skin Biopsy Samples and Nasal Swabs.

Pure neuritic leprosy (PNL) often remains underdiagnosed due to the lack of simple, reliable diagnostic tools to detect Mycobacterium leprae. This study aimed to investigate the utility of multiplex polymerase chain reaction (MPCR) in easily accessible and less invasive biopsy sites, including skin biopsy samples and nasal swabs (NSs), to detect M. leprae. A total of 30 (N = 30) clinically suspected and untreated patients with PNL were recruited. Nasal swabs and skin biopsy samples from the innervation territory of an "enlarged nerve" were collected. DNA was extracted and subjected to MPCR (targeting leprae-specific repetitive element [RLEP], 16S rRNA, and SodA genes) and RLEP-PCR (individual gene PCR). The PCR products were analyzed by 3% agarose gel electrophoresis. In 30 patients with clinically suspected PNL, 60% (N = 18) of skin biopsy samples and 53% (N = 16) of NSs were found positive for M. leprae DNA by MPCR, whereas only 23.3% (N = 7) of skin biopsy samples and 10% (N = 3) of NSs were found positive by RLEP-PCR. MPCR demonstrated a greater positivity rate than did RLEP-PCR for detection of M. leprae. Serologic positivity for anti-natural disaccharide-octyl conjugated with bovine serum albumin (ND-O-BSA) antibodies was 80% (16/20), including 35% (7/20) of PNL patients for which the skin MPCR was negative. Both serologic positivity and skin MPCR positivity were observed in 65% of patients (N = 20). Multiplex polymerase chain reaction is a useful tool for detection for M. leprae in skin biopsy samples and NSs in clinically suspected cases of PNL, with the added advantages of being less invasive and technically easier than nerve biopsy.

Linear immunoglobulin A/immunoglobulin G bullous dermatosis with celiac disease in a 26-year-old Filipino male

Linear immunoglobulin A/immunoglobulin G bullous dermatosis (LAGBD) is a rare form of autoimmune blistering disease characterized by circulating anti-keratinocyte cell surface antibodies from both the immunoglobulin A and immunoglobulin G. It presents as blisters, erosions, and pustules with erythematous lesions, primarily on the trunk and extremities. A 26-year-old Filipino male presented with a 4-year history of multiple pruritic vesicles on an erythematous base on the mentum spreading on the face, scalp, neck, upper trunk, and upper extremities. Skin biopsy and direct immunofluorescence suggest a diagnosis of LAGBD. The patient underwent esophagogastroduodenoscopy, which revealed duodenal villous atrophy. A small bowel biopsy revealed duodenal villous atrophy with a predominance of lymphocytes. He was treated with dapsone for two years with remarkable improvement. He was also advised to do a strict, lifelong gluten-free diet. After a 5-year follow-up, he only experienced occasional very mild flares treated with topical clobetasol 5% cream. We present a rare case of a patient with LAGBD with celiac disease. Systemic involvement, particularly gastroenteropathy, should also be investigated. Dapsone and a gluten-free diet have been the primary treatment modalities for this case.

Linear immunoglobulin A/immunoglobulin G bullous dermatosis with celiac disease in a 26-year-old Filipino male

Linear immunoglobulin A/immunoglobulin G bullous dermatosis (LAGBD) is a rare form of autoimmune blistering disease characterized by circulating anti-keratinocyte cell surface antibodies from both the immunoglobulin A and immunoglobulin G. It presents as blisters, erosions, and pustules with erythematous lesions, primarily on the trunk and extremities. A 26-year-old Filipino male presented with a 4-year history of multiple pruritic vesicles on an erythematous base on the mentum spreading on the face, scalp, neck, upper trunk, and upper extremities. Skin biopsy and direct immunofluorescence suggest a diagnosis of LAGBD. The patient underwent esophagogastroduodenoscopy, which revealed duodenal villous atrophy. A small bowel biopsy revealed duodenal villous atrophy with a predominance of lymphocytes. He was treated with dapsone for two years with remarkable improvement. He was also advised to do a strict, lifelong gluten-free diet. After a 5-year follow-up, he only experienced occasional very mild flares treated with topical clobetasol 5% cream. We present a rare case of a patient with LAGBD with celiac disease. Systemic involvement, particularly gastroenteropathy, should also be investigated. Dapsone and a gluten-free diet have been the primary treatment modalities for this case.

Clinicopathological concordance of mucocutaneous manifestations in people living with HIV: A cross-sectional study.

To describe the frequency and clinicopathological concordance of mucocutaneous manifestations in people living with HIV (PLWH) and its correlation with CD4+ T lymphocyte count and HIV viral load. Cross-sectional study of patients diagnosed with HIV infection who underwent skin biopsy for histopathological study from 1992 to 2022. Skin diseases were categorized as opportunistic and sexually transmitted infections, inflammatory dermatoses, benign cutaneous neoplasms, and premalignant and malignant cutaneous neoplasms. Clinicopathological concordance was classified as complete, partial or discordant. Frequency of skin diseases are presented by category and according to lymphocyte CD4+ count and HIV viral load. A total of 659 patients were included of whom 88.5% (n = 583) were male. The most frequent diagnostic category was opportunistic or sexually transmitted infections in 34% (n = 224) and the most frequently found condition was Kaposi sarcoma in 17% (n = 112). Clinicopathological concordance was complete in 53.7% (n = 354) of cases, partial in 26.7% (n = 176) and discordant in 19.6% (n = 129). Among the 282 patients with available serological data, 58.9% (n = 166), 23.8% (n = 67) and 17.4% (n = 49) had CD4+ counts below 200, between 200 and 499, and above 500 cells/μl, respectively. Although there is a high variability in skin conditions which people with HIV may present, there was a high rate of clinicopathological concordance (80.4%). We emphasize the importance of diagnostic skin biopsies due to their diverse morphological presentation. The frequency of skin diseases in PLWH depending on different clinical settings should aid the clinician in reaching an adequate diagnosis in this population.

Clinical management and case review of a presumptive novel clinical presentation of protothecosis in donkeys causing ulcerated nodular lesions in the ear pinnae of 18 animals

AbstractThis is a retrospective case series that describes a novel syndrome seen in 18 donkeys in Morocco that presented to this author,'s clinic with ulcerated nodular lesions of the ear pinnae. In the majority of cases, the lesions are confined to the ears, they are always bilateral and can occasionally progress to other areas of the body. Macroscopically, the lesions in all 18 donkeys are very uniform in presentation, even if the size of the nodules varies. This case series reviews the presentation, investigation, treatment and outcome for 18 cases presented to these authors’ clinics from 2011 to 2021. Skin biopsies from a subset of eight cases showed similar changes in chronic pyogranulomatous, dermatitis with myriad intra‐ and extra‐histiocytic organisms, the morphology of which is most consistent with that of Prototheca spp. infection. This is a novel presentation that represents a significant welfare issue for donkeys, as well as having important economic consequences for owners in the developing world.

Clinical management and case review of a presumptive novel clinical presentation of protothecosis in donkeys causing ulcerated nodular lesions in the ear pinnae of 18 animals

AbstractThis is a retrospective case series that describes a novel syndrome seen in 18 donkeys in Morocco that presented to this author,'s clinic with ulcerated nodular lesions of the ear pinnae. In the majority of cases, the lesions are confined to the ears, they are always bilateral and can occasionally progress to other areas of the body. Macroscopically, the lesions in all 18 donkeys are very uniform in presentation, even if the size of the nodules varies. This case series reviews the presentation, investigation, treatment and outcome for 18 cases presented to these authors’ clinics from 2011 to 2021. Skin biopsies from a subset of eight cases showed similar changes in chronic pyogranulomatous, dermatitis with myriad intra‐ and extra‐histiocytic organisms, the morphology of which is most consistent with that of Prototheca spp. infection. This is a novel presentation that represents a significant welfare issue for donkeys, as well as having important economic consequences for owners in the developing world.

Non-Invasive Paraclinical Diagnosis of Hepatocutaneous Syndrome in a Dog

A 14-year-old, female spayed Bichon Maltese with no other known previous pathologies was presented for dermatological examination after being referred from a private clinic with the suspicion of generalized, treatment-resistant demodicosis. Upon presentation and clinical examination, multiple deep skin scrapings were performed, returning negative parasitological results. Complete blood count and serum biochemistry revealed mild hepatic damage. Abdominal ultrasound revealed an abnormal echostructure of the liver displaying a honeycomb or Swiss cheese-like pattern, reported as pathognomonic for hepatocutaneous syndrome. The owner declined any further paraclinical examination, including skin biopsy and histopathological examination, requesting a treatment protocol that could be pursued at home, considering the age of the dog and its reactive behavior during the examination. The present case report highlights a non-invasive method of diagnosing the hepatocutaneous syndrome in a dog by clinical examination, routine blood testing, and ultrasound assessment of the abdomen, in the absence of the possibility of doing a histopathological diagnosis.

Non-Invasive Paraclinical Diagnosis of Hepatocutaneous Syndrome in a Dog

A 14-year-old, female spayed Bichon Maltese with no other known previous pathologies was presented for dermatological examination after being referred from a private clinic with the suspicion of generalized, treatment-resistant demodicosis. Upon presentation and clinical examination, multiple deep skin scrapings were performed, returning negative parasitological results. Complete blood count and serum biochemistry revealed mild hepatic damage. Abdominal ultrasound revealed an abnormal echostructure of the liver displaying a honeycomb or Swiss cheese-like pattern, reported as pathognomonic for hepatocutaneous syndrome. The owner declined any further paraclinical examination, including skin biopsy and histopathological examination, requesting a treatment protocol that could be pursued at home, considering the age of the dog and its reactive behavior during the examination. The present case report highlights a non-invasive method of diagnosing the hepatocutaneous syndrome in a dog by clinical examination, routine blood testing, and ultrasound assessment of the abdomen, in the absence of the possibility of doing a histopathological diagnosis.

Proteome profiling of cutaneous leishmaniasis lesions due to dermotropic Leishmania donovani in Sri Lanka

BackgroundCharacterization of the host response in cutaneous leishmaniasis (CL) through proteome profiling has gained limited insights into leishmaniasis research compared to that of the parasite. The primary objective of this study was to comprehensively analyze the proteomic profile of the skin lesions tissues in patients with CL, by mass spectrometry, and subsequent validation of these findings through immunohistochemical methods.MethodsEight lesion specimens from leishmaniasis-confirmed patients and eight control skin biopsies were processed for proteomic profiling by mass spectrometry. Formalin-fixed paraffin-embedded lesion specimens from thirty patients and six control skin specimens were used for Immunohistochemistry (IHC) staining. Statistical analyses were carried out using SPSS software. The chi-square test was used to assess the association between the degree of staining for each marker and the clinical and pathological features.ResultsSixty-seven proteins exhibited significant differential expression between tissues of CL lesions and healthy controls (p < 0.01), representing numerous enriched biological processes within the lesion tissue, as evident by both the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Among these, the integrated endoplasmic reticulum stress response (IERSR) emerges as a pathway characterized by the up-regulated proteins in CL tissues compared to healthy skin. Expression of endoplasmic reticulum (ER) stress sensors, inositol-requiring enzyme-1 (IRE1), protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6 (ATF6) in lesion tissue was validated by immunohistochemistry.ConclusionsIn conclusion, proteomic profiling of skin lesions carried out as a discovery phase study revealed a multitude of probable immunological and pathological mechanisms operating in patients with CL in Sri Lanka, which needs to be further elaborated using more in-depth and targeted investigations. Further research exploring the intricate interplay between ER stress and CL pathophysiology may offer promising avenues for the development of novel diagnostic tools and therapeutic strategies in combating this disease.

Elevated cutaneous expression of stem cell factor in chronic spontaneous urticaria: a prospective cohort study.

Tissue expression of endothelial cell (EC) markers of microcirculatory changes in CSU is poorly investigated. to explore the expression of specific EC markers (stem cell factor (SCF), vascular endothelial growth factor (VEGF) and membrane attack complex (MAC)) in CSU-L and CSU-NL skin through immunohistochemistry (IHC) and in serum. Lesional (L) and non-lesional (NL) skin biopsies from CSU patients and HCs were studied for the IHC expression of SCF, VEGF and MAC in CSU patients (n = 23) and healthy controls (HCs, n = 9). In this population, we also investigated blood levels of VEGF and SCF. Patients were also assessed for clinical characteristics, disease activity, and markers of autoimmune CSU (aiCSU). Epidermal SCF reactivity was significantly higher in CSU-L skin compared to HC skin (p=0.026). In the dermis, SCF immunoreactivity was seen particularly on endothelial, perivascular and epithelial cells. In CSU-L skin, mean perivascular SCF stainings were significantly more intense compared to HCs (p<0.001). Furthermore, CSU-NL skin also showed significantly higher SCF stainings on dermal perivascular cells compared to HCs (p<0.001). CSU patients had the highest SCF immunoreactivity scores in the epidermis and/or on dermal ECs. These patients did not have significantly higher SCF serum levels. This is the first study to show elevated cutaneous expression of SCF in chronic spontaneous urticaria. These findings underline the potential therapeutic possibilities of anti-KIT antibodies in CSU treatment.

ERG regulates lymphatic vessel specification genes and its deficiency impairs wound healing-associated lymphangiogenesis.

Rarefaction of blood and lymphatic vessels in the skin has been reported in SSc (systemic sclerosis, scleroderma). ERG and FLI1 are important regulators of angiogenesis, but their role in lymphatic vasculature is less known. The goal of this study was to determine the role of ERG and FLI1 in postnatal lymphangiogenesis and SSc lymphatic system defects. Immunofluorescence was used to detect ERG and FLI1 in SSc and healthy control (HC) skin biopsies. Transcriptional analysis of ERG or FLI1 silenced human dermal lymphatic endothelial cells (LECs) was performed using microarrays. Effects of ERG/FLI1 deficiency on in vitro tubulogenesis in human dermal LECs was examined using a Matrigel assay. Erg and Fli1 endothelial specific knockouts and Erg lymphatic specific knockouts were generated to examine vessel regeneration in mice. ERG and FLI1 protein levels were reduced in the blood and lymphatic vasculature in SSc skin biopsies. ERG was shown to regulate genes involved in lymphatic vessel specification, including VEGFR3/FLT4, LYVE-1, SOX18, and PROX1, while FLI1 enhanced the function of ERG. ERG/FLT4 pathway regulated in vitro tubulogenesis in human LECs. Deficiency of Erg or Fli1 similarly impaired the function of blood vessels in mice. However, only Erg deficiency affected the regeneration of lymphatic vessels during wound healing. ERG and FLI1 are essential regulators of blood and lymphatic vessel regeneration. Deficiency of ERG and FLI1 in SSc endothelial cells, may contribute to impairment of blood and lymphatic vasculature in SSc patients.

A skin-specific α-Synuclein seeding amplification assay for diagnosing Parkinson’s disease

The seeding amplification assay (SAA) has recently emerged as a valuable tool for detecting α-synuclein (αSyn) aggregates in various clinically accessible biospecimens. Despite its efficiency and specificity, optimal tissue-specific conditions for distinguishing Parkinson’s disease (PD) from non-PD outside the brain remain underexplored. This study systematically evaluated 150 reaction conditions to identify the one with the highest discriminatory potential between PD and non-synucleinopathy controls using skin samples, resulting in a modified SAA. The streamlined SAA achieved an overall sensitivity of 92.46% and specificity of 93.33% on biopsy skin samples from 332 PD patients and 285 controls within 24 h. Inter-laboratory reproducibility demonstrated a Cohen’s kappa value of 0.87 (95% CI 0.69–1.00), indicating nearly perfect agreement. Additionally, αSyn seeds in the skin were stable at −80 °C but were vulnerable to short-term exposure to non-ultra-low temperatures and grinding. This study thoroughly investigated procedures for sample preprocessing, seed amplification, and storage, introducing a well-structured experimental framework for PD diagnosis using skin samples.

Immunomorphological insights into clinical variants of bullous pemphigoid in Moscow Region patients.

Bullous Pemphigoid (BP) is an autoimmune blistering dermatosis in which the pathogenesis is primarily characterized by the production of autoantibodies IgG and IgE against hemidesmosomal proteins (BP180 and BP230) and the disruption of T-cell immune response regulation. [1] The classical understanding of the clinical course of BP has undergone significant transformation in recent years due to the identification of numerous conditions that do not exhibit typical clinical presentations but are diagnosed as BP based on immunofluorescences results. Often, when an atypical clinical form of BP develops, a specialist physician may not have grounds to include BP in the differential diagnosis. Consequently, specific diagnostic tests (such as immunomorphological examinations of skin biopsies) that would allow for the verification of this blistering dermatosis are not performed for the patient. Clearly, due to the absence of an accurate diagnosis, patients do not receive the necessary therapy. There is currently no information in the world literature regarding the frequency of atypical forms of BP. However, it is known that bullous pemphigoid is a relatively common blistering dermatosis in the population of European countries, with a prevalence ranging from 2.4 to 66 cases per million people, depending on the region. [2]