Neurosyphilis (NS), caused by Treponema pallidum, results in irreversible neurological damage. This study elucidated NS pathogenesis via cerebrospinal fluid (CSF) proteomic analysis comparing NS, suspected neurosyphilis (spNS), and non-neurosyphilis (nNS) controls by using liquid chromatography-tandem mass spectrometry (LC-MS/MS), public data set PXD033034, and ELISA validation. Of 1261 quantified proteins in the CSF, 234 were differentially expressed in NS, with 189 downregulated and enriched in lysosomal, axon guidance, and neurodegeneration pathways. Three previously identified CSF biomarkers of neurosyphilis, i.e., SEMA7A, SERPINA3, and ITIH4, were replicated. Key proteins in the lysosome pathway, including PSAP, CTSL, NPC2, and DNASE2, were significantly downregulated in the CSF of NS patients, and spNS patients presented a high CSF IgG index (spNS-hi-IgG-i). We also identified EPHA4, a key protein in the axon guidance pathway, as significantly downregulated in the CSF of NS patients. A positive correlation between PSAP and EPHA4 suggested a potential impact of lysosomal function on axonostasis in NS. ROC analysis revealed PSAP and DNASE2 as potential biomarkers for assessing neurodegeneration in NS and spNS-hi-IgG-i. These findings suggest that disruptions in lysosomal and axonal processes may contribute to neurodegeneration in NS, and the identified biomarkers hold potential as diagnostic indicators and therapeutic targets.

Lysine crotonylation, particularly on histones, has recently emerged as a prominent focus in post-translational modification research. While it has been extensively studied in oncology, its role in skin diseases remains largely unexplored. To address this gap, we enrolled 45 psoriasis patients from outpatient clinics and compared crotonylation profiles between lesional and non-lesional skin tissues. Although many modifications were conserved across both tissue types, several differences were observed. We identified 100 upregulated and 76 downregulated lysine crotonylation sites in psoriatic lesions. The most significantly upregulated site was detected in COL6A3 (ratio = 3.07, p = 1.73 × 10-2), while the most significantly downregulated site was found in S100A9 (ratio = 0.14, p = 3.61 × 10-5). Bioinformatics analysis further suggested enrichment of crotonylated proteins in the ribosome pathway within psoriatic lesions. Overall, this study offers preliminary evidence of altered lysine crotonylation in psoriatic skin and suggests its potential involvement in psoriasis pathogenesis.

Studies have indicated a relationship between bullous pemphigoid (BP) and hypertension, but the findings remain controversial. To examine this association, we conducted a systematic review using studies from PubMed, EMBASE, Web of Science, and the Cochrane Library, applying a random-effects model while performing subgroup and sensitivity analyses to explore potential sources of heterogeneity. Subgroup analyses were performed by country, data source, and sample size. The quality of evidence was evaluated using the Newcastle-Ottawa Scale. The review protocol was registered in PROSPERO (ID: CRD42024573911). The analysis included 20 studies, primarily consisting of case-control studies from Europe and Asia, encompassing 72,981,822 participants, of whom 29,199 had BP. The mean ages of the BP group and the non-BP group were 74.62 and 74.25 years, respectively. Random-effects meta-analysis demonstrated a significant association between BP and hypertension (odds ratio [OR] = 1.13, 95

Purpose:To investigate the correlation between the presence of the Koebner phenomenon (KP) and clinical features of patients with vitiligo. Patients and Methods:The clinical characteristic data, including age, age of onset, disease duration, gender, clinical stage, clinical type, family history, and comorbid immune-related diseases, of 1472 patients with/without KP were analyzed with SPSS 17.0 software. Results:Of the 1472 patients, 290 (19.70%) were positive for KP. The clinical course (6.95 vs 5.62, P = 0.015), percentage of patients with progressive stage (78.97% vs 70.05%, P = 0.002), the acrofacial type (4.49% vs 1.69%, P = 0.004), comorbid immune-related diseases (28.29% vs 19.04%, P = 0.001) and lesion area ≥2% (47.24% vs 38.24%, P = 0.005) in KP-positive group were significantly greater than those in KP-negative group. Binary logistic regression analysis found that progressive stage (P = 0.003, OR = 1.60, 95% confidence interval (CI): 1.17-2.18), area of skin lesion ≥2% (P = 0.008, OR = 1.44, 95% CI: 1.10-1.88) and comorbid immune-related diseases (P = 0.001, OR = 1.63, 95% CI: 1.21-2.20) were significantly associated with KP. Conclusion:The presence of KP in patients with vitiligo is associated with clinical progression, the acrofacial type, comorbid immune-related disease and a larger lesion area. This study suggested the presence of KP may be an indicator of disease activity and aggression, and underlay its importance in the management of disease.

BACKGROUND:The pathogenesis of psoriasis is incompletely understood. Growing evidence suggests the involvement of stromal cells in the inflammatory process. OBJECTIVES:To investigate the roles of stromal cells, including fibroblasts, vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), in the psoriatic inflammatory microenvironment, and the possible underlying mechanisms involved. METHODS:We used a combination of single-cell, spatial transcriptome and bulk RNA sequencing of lesional and nonlesional skin samples from patients with psoriasis vulgaris (PV) and healthy skin samples from unaffected individuals. RESULTS:By analysing transcriptomes from 364 098 single cells, we uncovered WNT5A+ (Wnt-5a) fibroblasts, ITIH5+ (inter-α-trypsin inhibitor heavy chain 5) VECs and VCAN+ (versican) VSMCs, with significantly increased proportions of these cells in the papillary dermis of lesional psoriatic skin. We defined eight unique subclusters of fibroblasts in the skin and observed a shift of WIF1+ (Wnt inhibitory factor 1) fibroblasts toward WNT5A+ fibroblasts, with abnormal activation of the noncanonical Wnt signalling pathway and increased angiogenic and proinflammatory capabilities. VSMCs were able to undergo phenotypic transformation from a contractile to a synthetic phenotype during the development of psoriatic inflammation. ITIH5+ VECs and VCAN+ VSMCs were found to have an essential role in regulating angiogenesis and vascular remodelling in the pathological changes seen in PV. Ligand receptor analyses found that WNT5A+ fibroblasts are extensively implicated in interactions with various skin cell types, especially TIH5+ VECs and VCAN+ VSMCs in the papillary dermis. CONCLUSIONS:Interactions of stromal cells in the papillary dermis were identified as possible pathogenic elements in PV. Improving the inflammatory microenvironment by targeting stromal cells might be a potential treatment strategy in PV.

Background: Bullous pemphigoid (BP) is a life-threatening chronic relapsing autoimmune blistering disease. Recently, metabolomics research has been widely applied to autoimmune skin diseases.This research aims to investigate the differential metabolites in the plasma of BP patients compared to healthy individuals and to identify the metabolic pathways enriched in BP, thereby providing new insights into the pathogenesis of BP. Methods: We collected plasma samples from 32 BP patients and 35 healthy controls, using untargeted metabolomics to Identify differential metabolites, and their metabolic and signal transduction pathways were determined through KEGG pathway enrichment analysis. Results: Analysis identified 27 different metabolites between BP and normal groups. Significant changes in metabolite levels included steroids, D-Sorbitol, fatty acids, benzenes and phenols, and Prenol lipids. Steroids were uniformly upregulated, while fatty acids were uniformly downregulated. KEGG pathway analysis identified 15 significantly different pathways (p < 0.05) between the BP and normal group, including amino acid metabolism, glycerophospholipid metabolism, and steroid hormone biosynthesis pathways. Conclusion: This study utilized metabolomics analysis to reveal the differences in plasma metabolites and characteristic metabolic pathways between BP patients and healthy controls. These findings provide new insights into the pathogenesis of BP and may inform the diagnosis, treatment, and long-term management of the disease.

Immune-related skin diseases represent a collective of dermatological disorders intricately linked to dysfunctional immune system processes. These conditions are primarily characterized by an immoderate activation of the immune system or deviant immune responses, involving diverse immune components including immune cells, antibodies, and inflammatory mediators. However, the precise molecular dysregulation underlying numerous individual cases of these diseases and unique subsets respond under disease conditions remains elusive. Comprehending the mechanisms and determinants governing the homeostasis and functionality of diseases could offer potential therapeutic opportunities for intervention. Mass cytometry enables precise and high-throughput quantitative measurement of proteins within individual cells by utilizing antibodies labeled with rare heavy metal isotopes. Imaging mass cytometry employs mass spectrometry to obtain spatial information on cell-to-cell interactions within tissue sections, simultaneously utilizing more than 40 markers. The application of single-cell mass cytometry presents a unique opportunity to conduct highly multiplexed analysis at the single-cell level, thereby revolutionizing our understanding of cell population heterogeneity and hierarchy, cellular states, multiplexed signaling pathways, proteolysis products, and mRNA transcripts specifically in the context of many autoimmune diseases. This information holds the potential to offer novel approaches for the diagnosis, prognostic assessment, and monitoring responses to treatment, thereby enriching our strategies in managing the respective conditions. This review summarizes the present-day utilization of single-cell mass cytometry in studying immune-related skin diseases, highlighting its advantages and limitations. This technique will become increasingly prevalent in conducting extensive investigations into these disorders, ultimately yielding significant contributions to their accurate diagnosis and efficacious therapeutic interventions.

Pemphigus vulgaris (PV) stands as a rare autoimmune bullous disease, while the precise underlying mechanism remains incompletely elucidated. High-throughput proteomic methodologies, such as LC-MS/MS, have facilitated the quantification and characterisation of proteomes from clinical skin samples, enhancing our comprehension of PV pathogenesis. The objective of this study is to elucidate the signalling mechanisms underlying PV through proteomic analysis. Proteins and cell suspension were extracted from skin biopsies obtained from both PV patients and healthy volunteers and subsequently analysed using LC-MS/MS and scRNA-seq. Cultured keratinocytes were treated with PV serum, followed by an assessment of protein expression levels using immunofluorescence and western blotting. A total of 880, 605, and 586 differentially expressed proteins (DEPs) were identified between the lesion vs. control, non-lesion vs. control, and lesion vs. non-lesion groups, respectively. The oxidative phosphorylation (OXPHOS) pathway showed activation in PV. Keratinocytes are the major cell population in the epidermis and highly expressed ATP5PF, ATP6V1G1, COX6B1, COX6A1, and NDUFA9. In the cellular model, there was a notable increase in the expression levels of OXPHOS-related proteins (V-ATP5A, III-UQCRC2, II-SDHB, I-NDUFB8), along with STAT1, p-STAT1, and p-JAK1. Furthermore, both the OXPHOS inhibitor metformin and the JAK1 inhibitor tofacitinib demonstrated therapeutic effects on PV serum-induced cell separation, attenuating cell detachment. Metformin notably reduced the expression of V-ATP5A, III-UQCRC2, II-SDHB, I-NDUFB8, p-STAT1, p-JAK1, whereas tofacitinib decreased the expression of p-STAT1 and p-JAK1, with minimal impact on the expression of V-ATP5A, III-UQCRC2, II-SDHB, and I-NDUFB8. Our results indicate a potential involvement of the OXPHOS and JAK-STAT1 pathways in the pathogenesis of PV.

目的 探讨中老年大疱性类天疱疮(bullous pemphigoid,BP)患者与湿疹患者的临床特征,分析BP180抗体检测对两种疾病的临床意义.方法 回顾性分析安徽医科大学第一附属医院2021年1—6月收治的40例中老年BP患者及40例湿疹患者的基本信息、病程、临床表现、伴发疾病、血清BP180抗体指数等临床资料并进行比较.结果 中老年BP患者和湿疹患者临床皮损表现不典型,BP组BP180抗体指数显著高于湿疹组(P＜0.05),血清BP180抗体指数与BP病情严重程度有相关性,BP组和湿疹组最常见伴发疾病分别为神经系统疾病(27.50%)和心血管系统疾病(27.50%).结论 中老年BP患者合并神经系统疾病多见,早期皮损不典型,易和湿疹混淆;BP180抗体检测对于早期中老年BP和湿疹的鉴别诊断有一定的意义,可作为BP病情评估的指标.

目的 研究天疱疮患者的临床特征,分析桥粒芯糖蛋白1抗体(desmoglein 1,Dsg1)和桥粒芯糖蛋白3抗体(desmoglein 3,Dsg3)ELISA检测结果与天疱疮分型及严重程度之间的关联.方法 选取2021年1-12月安徽医科大学第一附属医院收治的50例天疱疮患者,根据临床表现、实验室指标对天疱疮进行分型和分级,对诱发因素、伴发疾病、皮肤感染情况、Dsg1及Dsg3抗体指数等进行回顾性分析.结果 50例天疱疮患者中寻常型天疱疮39例、红斑型天疱疮8例、落叶型天疱疮2例和副肿瘤性天疱疮1例;轻度28例,中度11例,重度11例;常见诱发因素和糖皮质激素不规范使用有关,占比20％(10/50);最常见皮肤感染菌为金黄色葡萄球菌,检出率为18％(9/50).不同类型天疱疮患者Dsg3抗体指数差异有统计学意义(Z=-3.481,P＜0.001);不同严重程度天疱疮患者Dsg1及Dsg3抗体差异有统计学意义(P值分别为0.002、0.024).结论 天疱疮患者治疗中要注重糖皮质激素的正确使用,皮肤感染在天疱疮患者中较为常见,Dsg1及Dsg3抗体检测在天疱疮患者中具有较高的阳性率,Dsg1及Dsg3抗体指数可作为天疱疮病情评估的指标.

目的 探讨血清网膜素-1水平在银屑病患者中的分布,分析其与代谢性疾病之间的关联.方法 选择2019年1月-2020年12月就诊的银屑病患者作为研究对象.将患者按照PASI评分、有无合并代谢综合征(metabolic syndrome,MetS)进行分组,收集患者一般资料、血生化指标,采用酶联免疫吸附法测定血清网膜素-1水平.结果 BMI、腰围、血清总胆固醇、血清网膜素-1水平在轻、中、重度银屑病患者中的分布差异有统计学意义(P＜0.05).是否合并MetS的两组患者在BMI、腰围、收缩压、舒张压水平分布上的差异有统计学意义(P＜0.05).多元线性回归分析结果显示:血清网膜素-1水平每上升1个水平,腰围降低0.17(95％CI:0～0.34),收缩压降低0.73(95％CI:-0.06～1.41),甘油三酯降低0.03(95％CI:0.01～0.05),其中血清网膜素-1水平对收缩压的影响最大(标准化偏回归系数=0.163).二分类Logistic回归分析结果显示:网膜素-1水平每上升1个三分位数,银屑病患者合并MetS风险的OR=0.64(95％CI:0.46～0.89).结论 银屑病患者网膜素-1水平与其病情严重程度、代谢性指标及MetS之间存在关联,临床早期监测血清网膜素-1水平变化并采取针对性干预措施,可能有助于降低银屑病患者代谢性疾病的发生率.

Background Immunoglobulin-A vasculitis (IgAV) is an immune-related systemic vasculitis with an unclear etiology. Genetic predisposition is now considered to be closely associated with the development of the disease, and it is essential to reveal the relationship between them. To explore the role of heredity in the disease, we performed a genome-wide association study (GWAS) of 496 IgAV cases and 7165 controls using an Illumina Infinium Global Screening Array chip. Methods In the first stage of analysis, a significant correlation between the major histocompatibility complex (MHC) and IgAV was observed. Subsequently, human leukocyte antigen (HLA) analysis was conducted using a new large-scale Han-MHC reference panel. Fine mapping of IgAV risk in the MHC region indicated that two amino acid positions, 120 and 11, of HLA-DRB1 and three potential HLA alleles (HLA-DRB1*04, HLA-DRB1*16, and HLA-DRB1*16:02) were significantly associated. Results Further stepwise conditional analysis demonstrated that 3 amino acid positions (120, 26, 96) of HLA-DRB1 and 6 HLA-DRB1 alleles (HLA-DRB1*04, HLA-DRB1*16, HLA-DRB1*01, HLA-DRB1*12:02, HLA-DRB1*10, and HLA-DRB1*15:02) were independent signals. Among them, the most significant signal was HLA-DRB1 amino acid Ser120 (OR = 1.59, p = 3.19 x 10(-8)); no independent signal in the MHC region except for HLA-DRB1 was found. Conclusions Our study confirms that the pathogenesis of IgAV has a genetic component and that HLA-DRB1 is strongly associated with susceptibility to IgAV.

目的 通过检测降钙素原及白细胞介素(IL)-6在泛发性脓疱型银屑病(GPP)病人血清中的表达水平,为病情和疗效评估寻找标志物.方法 收集安徽医科大学第一附属医院2017年1月至2019年12月收治的132例住院银屑病病人的病历资料,入组病人包括寻常型银屑病(PV)46例,红皮病型银屑病(EP)33例,以及GPP 53例,并针对各组病人的年龄、性别和发病年龄等人口学特征以及外周血中降钙素原及IL-6含量进行统计分析.结果 治疗前GPP病人的降钙素原、IL-6含量分别为(0.41±0.14)μg/L、(57.75±11.48)ng/L,显著高于PV组的(0.11±0.05)μg/L、(21.76±8.28)ng/L及EP组的(0.14±0.04)μg/L、(32.57±9.39)ng/L(P<0.05).治疗后GPP病人降钙素原、IL-6水平均明显降低至(0.03±0.01)μg/L、(4.22±1.13)ng/L,较治疗前差异有统计学意义(P<0.05).ROC分析显示:降钙素原、IL-6及其联合应用对GPP病人病情严重程度的评估有较高价值,其AUC 95％CI分别为0.738(0.569,0.957)、0.787(0.661,0.937)、0.831(0.699,0.988).结论 与其他类型银屑病相比,降钙素原及IL-6在GPP中的表达显著升高,并在治疗后随病情好转下降,可作为GPP的病情和疗效评估标志物.