Increased CRHR1 expression on monocytes from patients with AA enables a pro-inflammatory response to corticotrophin-releasing hormone.

Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (n = 54) and controls (n = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, p = 0.002, chi-squared test). AA incidence was correlated to elevated CD14+ monocyte numbers (R = 0.092, p = 0.036) and markedly independently correlated with increased CRHR1 expression (R = 0.215, p = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration >1 year; p = 0.003, chi-squared test), and large lesion area (AA area >25%; p = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16+ CD3- NK cell numbers in AA patients' PBMCs (p = 0.010; 0.025, respectively). In vitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.

Thyroid Dysfunction and Alopecia Areata: A Genetic Prediction Causality Analysis Study.

BACKGROUND: Observational studies have suggested a correlation between alopecia areata (AA) and thyroid dysfunction (TD). However, the causal relationship between AA and TD remains uncertain. The purpose of this study is to investigate the causal relationship between these two conditions. Understanding the potential causal relationship between AA and TD is valuable for elucidating the pathogenesis of AA and for designing innovative methods to prevent and treat AA and its related complications. METHODS: All data for this two-sample Mendelian randomization (MR) study were sourced from public databases. This study selected hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, and Graves' disease as exposure factors, with AA as the outcome variable. Data for hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, Graves' disease, and AA were obtained from related genome-wide association studies (GWAS). Various MR analysis methods such as inverse variance weighted (IVW), MR-Egger, and weighted median were utilized. Additionally, Cochrane's Q test was used to detect heterogeneity in MR results, and the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy. A leave-one-out analysis was conducted to investigate the sensitivity of this association. RESULTS: We found statistically significant genetic predictions of AA with hypothyroidism, Hashimoto's thyroiditis, and subacute thyroiditis (IVW OR = 1.4009815, 95% confidence interval [CI]: 1.1210399-1.750829; p = 0.003030698, OR = 1.396101, 95% CI: 1.030134-1.89208; p = 0.03144273, OR = 0.732702, 95% CI: 0.604812-0.887634; p = 0.001483368). Furthermore, tests for pleiotropy showed no evidence of pleiotropy, enhancing the credibility of the study results. Finally, the leave-one-out test demonstrated the stability and robustness of this association. CONCLUSION: This study provides new evidence of a potential genetic link between thyroid issues and AA. By employing the two-sample MR method to eliminate confounding factors and reverse causation, unbiased results were obtained, confirming a causal relationship between hypothyroidism, Hashimoto's thyroiditis, subacute thyroiditis, and AA. This lays the foundation for further mechanistic studies and potential clinical applications. Future research should further explore the specific biological mechanisms between TD and the onset of AA.

Analysis of patient experiences regarding JAK inhibitors for atopic dermatitis, psoriasis, alopecia areata, and vitiligo.

The use of medications which target the JAK-STAT signaling pathway, also known as janus kinase (JAK) inhibitors, has rapidly increased in recent years. Patient perceptions, opinions, and concerns regarding the use of JAK inhibitors are largely uninvestigated. Our objective is to better understand patient concerns, reported side effects, and sentiments regarding the use of JAK inhibitors for dermatologic disease. The authors performed a cross-sectional analysis of the most frequented subreddits for dermatologic disease in which JAK inhibitors have obtained FDA approval (r/atopic dermatitis, r/psoriasis, r/alopecia areata, r/vitiligo, and r/eczeJAKS). The sentiment, central theme, and engagement level of each post was evaluated using previously utilized methods. Nine hundred twenty-three posts were analyzed, with the majority focusing on efficacy (433, 47%) and medication-related side effects (150, 16%). Other themes of interest to patients were Payment/Insurance (84, 9%), Study Results/News (69, 7%), Administration/Dosage (33, 4%), and Medication Interactions (31, 3%). The most frequently reported side effects were acne/folliculitis (24, 22%), nausea/gastrointestinal disturbance (11,10%), and fatigue/muscle aches (10, 9%). At the same time, the medication interactions garnering the most concern were sunscreens/facial moisturizers (5, 16%), topical calcineurin inhibitors (4, 13%), and Marijuana/THC (3, 9.%). This analysis highlights that patients are most concerned about the efficacy and side effects of JAK inhibitors in addition to issues regarding access to JAK inhibitors. Providers can use the insights gained from this study to address hesitancy better and guide comprehensive, patient-centered discussions with patients regarding JAK inhibitor use.

Causal links between 13 autoimmune diseases and graft dysfunction: A Mendelian randomization study.

Previous studies have suggested a possible link between autoimmune diseases and graft dysfunction; however, a causal link remains unclear. Exposure factors were set as 13 autoimmune diseases, and outcomes were set as graft dysfunction. Mendelian randomization was used to analyze the causal link between exposure and outcome. Alopecia areata and asthma were linked to graft dysfunction (odds ratio 0.828; 95% confidence interval 0.699-0.980; P = .029; odds ratio 1.79; 95% confidence interval 1.069-2.996; P = .027). At the same time, primary sclerosing cholangitis was found to be heterogeneous as an exposure factor (P = .009), but no heterogeneity or pleiotropy was found in other exposure factors. Our preliminary findings show 2 autoimmune diseases as risk factors for graft dysfunction, 1 autoimmune disease as a protective factor for graft dysfunction and the mechanisms remain to be understood.

Efficacy and safety of compound glycyrrhizin combined with topical minoxidil for alopecia areata: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Alopecia areata (AA) is a common autoimmune skin disease. Our study aimed to systematically evaluate the efficacy and safety of compound glycyrrhizin (CG) combined with topical minoxidil therapy in treating AA. METHODS: We searched the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Randomized controlled trials (RCTs) on CG combined with topical minoxidil therapy compared with topical minoxidil therapy alone for AA were included. The Cochrane Collaborative Network Tool was used to assess the risk of bias. Statistical analysis was completed using RevMan5.3 software and Stata 15.0 software. The GRADE system was used to evaluate the quality of evidence for outcomes. RESULT: 11 RCTs and 1189 patients were included. Compared with topical minoxidil therapy alone, CG combined with topical minoxidil therapy was more effective at improving the clinical efficacy (RR = 1.36, 95% CI [1.27, 1.45], p < 0.00001). The SALT score (MD = -10.09, 95% CI [-12.89, -7.30], p < 0.00001), serum TNF-α levels (MD = -0.99, 95% CI [-1.19, -0.39], p < 0.00001), serum IL-12 levels (MD = -8.84, 95% CI [-11.20, -6.47], p < 0.00001) and serum IFN-γ levels (MD = -7.44, 95% CI [-11.51, -3.37], p = 0.0003) were reduced, and the serum TGF-ß1 levels (MD = 2.40, 95% CI [1.24, 3.57], p < 0.0001) were increased. There were no significant differences in reported adverse events, including irritant contact dermatitis (RR = 0.51, 95% CI [0.25, 1.01], p = 0.05),' gastrointestinal reactions (RR = 2.47, 95% CI [0.49, 12.55], p = 0.28), lower limb edema (RR = 2.60, 95% CI [0.61, 11.06], p = 0.20), facial edema (RR = 2.33, 95% CI [0.61, 8.93], p = 0.22), or localized itching (RR = 0.56, 95% CI [0.18, 1.75], p = 0.32), between the two groups. CONCLUSION: The current evidence indicates that CG combined with topical minoxidil therapy is effective and safe for AA. However, owing to the suboptimal quality of the included studies, more high-quality and large-scale RCTs are needed for comprehensive analysis and further validation.

Assessing a measure for Quality of Life in patients with severe Alopecia Areata: a multicentric Italian study.

Objective: The prevalence of anxiety and depression in patients diagnosed with Alopecia Areata (AA) is very high and this significant burden of psychological symptoms threatens the Health-Related Quality of Life (HRQoL) of affected patients. Indeed, AA often does not produce significant physical symptoms, but it nonetheless disrupts many areas of mental health. Clinical assessment of disease severity may not reliably predict patient's HRQoL, nor may it predict the patient's perception of illness. For this reason, considerable effort has been made to apply and develop measures that consider patient's perception and assess the HRQoL of individuals affected by AA. The aim of this multicentric study was to provide the Italian version of the Skindex-16AA and to evaluate its psychometric properties in a clinical sample of consecutive patients with moderate-to-severe AA. Methods: This is a longitudinal, multicenter, observational study. Patients returned for follow-up visits at 4-, 12-, and 24-weeks. The analyses of the current work aimed to confirm the factorial structure of the Skindex-16AA. In the case of non-fit, an alternative structure for the model was proposed, using an Exploratory Graph Analysis and the Bayesian approach. Results: The sample was composed of 106 patients with AA. Alopecia Universalis was the most frequently diagnosed type of alopecia at all time points. The analyses on the Skindex-16AA revealed that a two-factor structure with eight items fit the data best (Bayesian Posterior Predictive Checking using 95% Confidence Interval for the Difference Between the Observed and the Replicated Chi-Square values = -6.246/56.395, Posterior Predictive P-value = 0.06), and reported satisfactory psychometric properties (i.e., internal consistency and convergent validity). Conclusion: The Skindex-8AA demonstrated optimal psychometric properties (i.e., convergent and construct validity, and test-retest reliability) measured in a sample of patients with AA, that may suggest that it is an appropriate tool to measure the HRQoL in AA patients. However, further studies are needed in order to confirm and tested other psychometric features of this tool.

Clinical and Sociodemographic Features of Alopecia Areata in Five Colombian Cities: An Analysis of the RENAAC Registry. / [Artículo traducido] Características clínicas y sociodemográficas de la alopecia areata en 5 ciudades colombianas: un análisis del RENAAC.

BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by non-scaring hair loss and preservation of hair follicles. The information available on disease course, and clinical features of AA is scarce worldwide, and almost nonexistent in Colombia. OBJECTIVE: To determine the clinical and sociodemographic characteristics of patients diagnosed with AA who presented to a dermatology consultation in five Colombian cities. MATERIAL AND METHODS: This was a retrospective and multicenter study on data from an ongoing National Registry of Alopecia Areata in Colombia (RENAAC) collected in Bogota, Cali, Cartagena, Barranquilla, and Medellin, Colombia from March 2022 through April 2023. Data was recorded in a standardized form by trained physicians. The variables were expressed as measures of central tendency and dispersion, and absolute and relative frequencies. RESULTS: A total of 562 patients were included, 59.4% of whom were women, aged between 15 and 49 years (63.9%) with a mean disease course of 1.7 years. The most common finding was multiple plaque (53.2%), the predominant AA subtype was patchy (71.4%), and 29.5% of the patients had a past dermatological history, 18.3% had a past endocrinological history, and 8.9% had a past psychiatric history. The treatments most widely used were steroid injections (76.4%), 5% topical minoxidil (46.4%), followed by high-potency corticosteroids (42.5%). STUDY LIMITATIONS AND CONCLUSIONS: AA was slightly predominant in women. As seen in other populations, this disease had an earlier onset in men vs women. Presentation in pediatric age was uncommon. The previous history of other dermatological diseases was checked in almost one third of the patients. Analysis of the co-presentation of AA with other autoimmune diseases is biased due to excluding patients with systemic erythematous lupus from the study.

Concurrent Eosinophilia Increases the Prevalence of Nail Abnormalities and Severity of Hair Loss in Patients With Alopecia Areata.

Background: The potential link between alopecia areata (AA) and eosinophilia is unclear, as well as its clinical manifestations in these patients' subsets. Methods: This is a monocentric retrospective observational study in which clinical and laboratory data were summarized and evaluated the AA subset with concurrent eosinophilia. Results: In a sample of 205 AA patients, 38 (18.5%) were classified as AA with eosinophilia. Interestingly, this subset of patients had a statistically higher prevalence of atopia and nail abnormalities (p < 0.05) than AA without eosinophilia. AA patients with eosinophilia had a 3.70 higher odds of more severe hair loss versus age- and gender-matched AA without eosinophilia. Conclusions: AA patients with eosinophilia had distinctive clinical and laboratory characteristics, so future studies may potentially explore the use of IL-5 inhibitors.

Mesenchymal Stem Cell Therapy in Alopecia Areata: Visual and Molecular Evidence from a Mouse Model.

Recent studies have highlighted the potential of Mesenchymal Stem Cells (MSCs) as an alternative treatment for Alopecia Areata (AA) due to their immunosuppressive properties. While MSCs have shown promise in cell experiments, their effectiveness in vivo remains uncertain. This study aims to validate local administration of MSC therapy's efficacy in AA treatment through animal experiments. AA was induced through Interferon-gamma (IFN-γ) administration in mice, and MSC treatment (MSCT)'s effects were assessed visually and through tissue analysis. The MSC-treated group showed more hair regrowth compared to the control (CTL) group. MSCT notably reduced local inflammatory cytokines (JAK1, JAK2, STAT1, STAT3, IFN-γR, IL-1ß, IL-16, IL-17α, and IL-18) in AA-induced mice's skin, but systemic cytokine levels remained unchanged. Furthermore, MSC treatment normalized the expression of Wnt/ß-catenin signaling pathway genes (LEF1 and ß-catenin) and growth factors (FGF7 and FGF2), which are crucial for hair cycle regulation. This study lays the groundwork for further exploring MSCs as a potential treatment for AA, but more research is needed to fully understand their therapeutic potential.

Preparation, solubility, and anti-inflammatory effects of a complex of diphenylcyclopropenone/ß-cyclodextrin derivatives as the treatment of alopecia areata.

Purpose: To investigate the preparation of inclusion complexes of diphenylcyclopropenone (DPCP)/ß-cyclodextrin (ß-CD) derivatives using a three-dimensional (3D) ball mill, and verify the inclusion behavior of the solid dispersion. Additionally, we aimed to investigate the effect of DPCP/ß-CDs complex formation on the spleens of male C57BL/6 mice in terms of anti-inflammatory effects. Methods: The inclusion complexes of DPCP with ß-CD and hydroxypropyl-ß-cyclodextrin (HPßCD) were prepared using a 3D ball mill. Powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to evaluate the solid-state properties. The solubility of the prepared DPCP/ß-CD and HPßCD complexes and the intermolecular interaction between DPCP and ß-CD derivatives in solution were assessed using 1H nuclear magnetic resonance (NMR). Furthermore, the anti-inflammatory effects of DPCPs in the prepared DPCP/CD complexes were investigated using spleens from male C57BL/6 mice, with measurement of interferon gamma (IFN-γ) secretion as an endpoint. Additionally, the protective effects of each drug on NIH-3T3 cells exposed to ultraviolet (UV) irradiation were examined. Results: Solid-state characterization confirmed the formation of inclusion complexes in the 3D ground mixture (3DGM) (DPCP/ß-CD = 1/1) and 3DGM (DPCP/HPßCD = 1/1) complexes through PXRD and IR analysis. The solubility of 3DGM (DPCP/ß-CD = 1/1) and 3DGM (DPCP/HPßCD = 1/1) was 17.5 µg/mL and 58.4 µg/mL, respectively, indicating higher solubility than that of DPCP alone. NMR analysis of 3DGM samples suggested that DPCP/ß-CD and DPCP/HPßCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. Regarding the anti-inflammatory activity of DPCP, 3DGM (DPCP/HPß-CD) showed anti-inflammatory effects at lower doses compared to 3DGM (DPCP/ß-CD) in terms of IFN-γ and NIH-3T3 cells injured by UV irradiation. Conclusion: We successfully formed inclusion complexes of DPCP/ß-CD and DPCP/HPßCD using the 3D ground mixture method. NMR analysis suggested that DPCP/ß-CD and DPCP/HPßCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. The anti-inflammatory activity of DPCP was more pronounced in 3DGM (DPCP/HPßCD) at lower doses compared to that in 3DGM (DPCP/ß-CD), indicating that the HPßCD derivatives were more effective in enhancing the anti-inflammatory properties of DPCP.

The genetic link between thyroid dysfunction and alopecia areata: a bidirectional two-sample Mendelian randomization study.

Background: Although descriptive studies have found an association between thyroid dysfunction (TD) and alopecia areata (AA), however, the causal relationship between TD and AA remains unclear. The purpose of this study is to investigate the causal relationship between the two and the specific directions. Methods: We performed large-scale, two-sample Mendelian randomization (MR) analyses to examine whether there was an association between TD (such as Graves' disease (GD), Hashimoto's thyroiditis (HT), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), etc.) and AA. Genome-wide association study (GWAS) summary statistics for TD and AA were from the IEU OpenGwas project. The inverse variance-weighted (IVW) method was used as the primary analysis method to evaluate the causality between TD and AA, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. In addition, sensitivity analyses were performed to assess the reliability of the study results. Results: Our study found that single nucleotide polymorphisms (SNPs) in HT (IVW OR = 1.396, 95% CI 1.030-1.892, P=0.031) and hypothyroidism (IVW OR = 1.431, 95% CI 1.138-1.799, P=0.002) significantly increased the risk of AA. Reverse MR analysis indicated that genetic susceptibility to AA (ß=-0.029, 95%CI=-0.051 to -0.007, P=0.009) may be a risk for TRH. Positive MR analysis observed no statistically significant causal relationship between other TD and AA (IVW P>0.05). Reverse MR analysis also showed no statistically significant association between AA and other TD (IVW P>0.05) other than TRH. Furthermore, additional sensitivity analyses were performed, including a leave-one-out test, a heterogeneity test, and a pleiotropy test to assess the robustness of the results. Conclusions: This study provides a very comprehensive analysis of the causal relationship between TD and AA, providing convincing genetic evidence to support the causal relationship between TD and alopecia areata. It reveals some causes of AA patients, which is of great significance for the management and treatment of AA patients.

Cedrol in ginger (Zingiber officinale) as a promising hair growth drug: The effects of oral and external administration on hair regeneration and its mechanism.

Ginger is an important cooking spice and herb worldwide, and scientific research has gradually confirmed the effect of ginger on preventing hair loss. Cedrol (CE) is a small sesquiterpene molecule in ginger and its external administration (EA) has shown hope in promoting hair growth, and alternative administration mode has become a potential treatment scheme to improve the efficacy of CE. The purpose of this study is to evaluate the effects of oral administration (OA) and EA of CE on hair regeneration of C57BL/6 alopecia areata (AA) mice induced by cyclophosphamide (CP) and to clarify the potential hair growth mechanism of CE in AA model in vitro and in vivo. The results showed that CE-OA has a shorter hair-turning black time and faster hair growth rate, and can lessen hair follicle damage induced by CP and promote hair follicle cell proliferation. Its effect is superior to CE-EA. At the same time, CE can increase the cytokines IFN-γ, IL-2, and IL-7 in the serum of mice, and decrease the expression of adhesion factors ICAM-1 and ELAM-1, thus alleviating the immunosuppression induced by CP. Mechanism research shows that CE regulates the JAK3/STAT3 signaling pathway, activates the Wnt3α/ß-catenin germinal center, and ameliorates oxidative stress induced by CP, thus promoting the proliferation of hair follicle cells and reversing AA. These results provide a theoretical basis for understanding the anti-AA mechanism of CE-OA, indicating that CE can be used as raw material for developing oral hair growth drugs.

Case report: Psoriasiform eczema with immune-mediated comorbidities treated with upadacitinib.

Immune-mediated comorbidities in patients with psoriasiform eczema are common. It can be challenging to manage multiple immune-mediated diseases, especially considering that biologic treatments are prone to causing paradoxical effects. The aim of this retrospective observational case series was to describe the course of both psoriasiform eczema and immune-mediated comorbidities in five patients treated with upadacitinib for psoriasiform dermatitis. Five patients, all male, were included. All the patients suffered from psoriasiform eczema. Moreover, two of the patients suffered from alopecia areata, two from vitiligo, one from ulcerative colitis and one from hidradenitis suppurativa. In all cases, the treatment with upadacitinib was rapidly effective on the eczema. The effectiveness on alopecia areata was good in both cases, while the results on vitiligo were only partial. The only case of ulcerative colitis achieved complete remission, while the case of hidradenitis suppurativa experience partial improvement. In conclusion, upadacitinib was effective in treating not only psoriasiform eczema, but also several immune mediated comorbidities. Additional studies are necessary to determine the efficacy of upadacitinib in alopecia areata, vitiligo and hidradenitis suppurativa.

Co-regulatory mechanisms and potential markers of oxidative stress-related genes in vitiligo and alopecia areata.

BACKGROUND: The specific role of oxidative stress (OS) in vitiligo and alopecia areata (AA) remains unclear. The aim of this study was to analyze and identify the key markers of OS in vitiligo and AA by bioinformatics. METHODS: We obtained vitiligo and AA datasets from gene expression omnibus (GEO) database. The difference-expressed genes of vitiligo and AA were identified by differential analysis, and the functions of difference-expressed genes were identified by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis. Subsequently, Veen package was used to obtain the intersection genes of OS-related genes with vitiligo and AA. Finally, we used CIBERSORT to assess the infiltration of immune cells in vitiligo and AA. RESULTS: Through enrichment analysis, we found that vitiligo and AA were mainly enriched in cell cycle and cell adhesion molecular channels. We identified KLB and EIF3C as key genes in OS regulation of vitiligo and AA, and found that KLB and EIF3C participate in disease progression by regulating T cells and neutrophils. CONCLUSIONS: According to our findings, KLB and EIF3C play a crucial role in the progression and development of vitiligo and AA, which have been identified as biomarkers and target for early diagnosis of patients.

Interleukin-33 links asthma to alopecia areata: Mendelian randomization and mediation analysis.

OBJECTIVE: The objective of this study is to elucidate the causal association between asthma and alopecia areata (AA) through the application of Mendelian randomization (MR) analysis, leveraging summary data from genome-wide association studies (GWAS). Additionally, it explores potential mediating factors. MATERIALS AND METHODS: Mendelian randomization (MR) analysis was employed to investigate the causal relationship between asthma and AA using genetic instrumental variables (IVs) for asthma, 91 circulating inflammatory proteins, and AA extracted from large-scale GWAS. The primary analytical approach utilized the inverse-variance weighted (IVW) method, supplemented by weighted median and MR-Egger methods to assess robustness. Tests for heterogeneity and pleiotropy were conducted to ensure result reliability. Furthermore, the study examined the mediating role of circulating inflammatory proteins in the asthma-AA relationship. RESULTS: The findings revealed an increased risk of AA among asthma patients (odds ratio (OR) = 14.070; 95% confidence interval (CI) = 1.410-140.435; P = 0.024). Interleukin-33 (IL-33) emerged as a significant mediator in the asthma-AA relationship, explaining 13.1% of the mediation effect. Bidirectional Mendelian randomization analyses did not establish a causal effect of AA on asthma occurrence. CONCLUSION: This study, utilizing Mendelian Randomization, elucidates the causal link between asthma and AA, highlighting the mediating role of IL-33. These findings underscore the importance of considering AA risk in asthma management and offer insights for potential therapeutic strategies targeting IL-33. Future research should explore additional biomarkers and mediating mechanisms between asthma and AA to enhance treatment approaches and patient quality of life.

Explore the genetic exposure to alopecia areata.

BACKGROUND: Alopecia areata is an autoimmune hair loss disorder with an incompletely understood etiology. Although trace elements, serum metabolites, and inflammatory factors are implicated in the disease, the potential causal relationships between these factors and alopecia areata require further investigation. METHODS: This study employed Mendelian randomization (MR), utilizing data from genome-wide association studies, to explore the causal relationships between 15 trace elements, 1400 serum metabolites, and 91 inflammatory factors and alopecia areata. The analysis was conducted using the inverse variance weighted (IVW) method complemented by various sensitivity analyses, including Cochran's Q test, MR-Egger regression intercept test, MR-PRESSO global test, and leave-one-out analysis, to assess the robustness of the results. RESULTS: MR analysis indicated a negative correlation between copper levels and the risk of developing alopecia areata (odds ratio = 0.86, 95% confidence interval: 0.75-0.99, p = 0.041). Additionally, causal relationships were identified between 15 serum metabolites and 6 inflammatory factors and the risk of alopecia areata (IVW, all p values < 0.05). CONCLUSION: This study provides genetic evidence of the relationships between trace elements, serum metabolites, and alopecia areata, underscoring the potential value of targeted therapeutic strategies and preventive measures. Future research should expand to diverse populations and further explore the specific roles of these biomarkers in the disease mechanism.

Current Protocols: Alopecia Areata Mouse Models for Drug Efficacy and Mechanism Studies.

Alopecia areata is the second most common form of hair loss in humans after androgenetic alopecia. Although a variety of animal models for alopecia areata have been described, currently the C3H/HeJ mouse model is the most commonly used and accepted. Spontaneous hair loss occurs in 15%-25% of older mice in which the lesions wax and wane, similar to the human disease, with alopecia being more common and severe in female mice. Full-thickness skin grafts from mice with spontaneous alopecia areata to young, normal-haired, histocompatible mice provide a highly reproducible model with progressive lesions that makes it useful for drug efficacy and mechanism-based studies. As alopecia areata is a cell-mediated autoimmune disease, transfer of cultured lymph node cells from affected mice to unaffected, histocompatible recipients also promotes disease development and provides an alternative, nonsurgical protocol. Protocols are presented to produce these models such that they can be used to study alopecia areata and to develop novel drug therapies. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Full-thickness skin grafts to reproducibly induce alopecia areata in C3H/HeJ mice Basic Protocol 2: Adoptive transfer of cultured lymphoid cells provides a nonsurgical method to induce alopecia areata in C3H/HeJ mice.