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Frontiers in Immunology 2024To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs),...
BACKGROUND
To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk.
METHODS
By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results.
RESULTS
Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility.
CONCLUSION
In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments and , are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.
Topics: Humans; Parkinson Disease; Mendelian Randomization Analysis; Autoimmune Diseases; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38774879
DOI: 10.3389/fimmu.2024.1370831 -
Clinical, Cosmetic and Investigational... 2024The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many... (Review)
Review
The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many pathological processes, such as tumors and autoimmune diseases. Recent studies also demonstrated that the defective functions of ER may lead to pigmentary diseases. Vitiligo is a depigmenting ailment skin disorder whose pathogenesis is now found to be associated with ER. However, the detailed mechanism is still unclear. In this review, we try to link the association between ER with its inter- and intra-organellar interactions in vitiligo pathogenesis and focus on the function, mechanism, and clinical potential of ER with vitiligo. Expand ER is found in melanocytes of vitiligo and ER stress (ERS) might be a bridge between oxidative stress and innate and adaptive immunity. Meanwhile, the tight association between ER and mitochondria or melanosomes in organelles levels, as well as genes and cytokines, is the new paradigm in the pathogenesis of vitiligo. This undoubtedly adds a new aspect to the understanding of vitiligo, facilitating the design of targeted therapies for vitiligo.
PubMed: 38774812
DOI: 10.2147/CCID.S459070 -
Boletin Medico Del Hospital Infantil de... 2024Vitiligo is a multifactorial disease characterized by the progressive loss of melanocytes. The worldwide prevalence ranges from 0.5% to 2%, and in children from 0% to...
BACKGROUND
Vitiligo is a multifactorial disease characterized by the progressive loss of melanocytes. The worldwide prevalence ranges from 0.5% to 2%, and in children from 0% to 2.16%. The objective of this study was to determine the variables associated with progression of vitiligo.
METHODS
A retrospective cohort was carried out where a random sample of records of pediatric patients with vitiligo from January 2016 to December 2020 was analyzed. The variables were studied: age at onset, sex, hereditary family history, personal history of thyroid diseases, time of evolution, classification, Köebner phenomena, mucosal vitiligo, halo nevus, premature graying and the presence of other dermatoses. The final state was classified as progression, stability, partial remission and complete remission.
RESULTS
574 children with vitiligo; 290 (50.5%) women, 284 (49.5%) men. Non-segmental vitiligo in 324 (56.4%), segmental vitiligo in 250 (43.6%). Mean age of onset 8.7 years (SD: 4.54). Median evolution time 6 months (25 percentile of 3 months and 75 percentile of 24 months). Family history 27 (4.70%). Thyroid disease 7 (1.21%). Evolution remained stable in 44 (7.7%), 68 (11.8%) had progression, 32 (5.6%) complete remission, 222 (38.7%) partial remission and 208 (36.2%) one consultation. Non-segmental vitiligo was obtained p < 0.028, younger age of onset p < 0.000, and none skin comorbidities p < 0.009.
CONCLUSIONS
The variables that were associated with a more progression were non-segmental vitiligo, early ages at the onset of the disease, and not presenting with other skin diseases.
Topics: Humans; Vitiligo; Male; Female; Retrospective Studies; Child; Prognosis; Child, Preschool; Age of Onset; Adolescent; Disease Progression; Cohort Studies; Infant; Thyroid Diseases
PubMed: 38768496
DOI: 10.24875/BMHIM.23000083 -
Dermatology and Therapy Jun 2024Vitiligo is a chronic autoimmune disease characterized by destruction of melanocytes, leading to skin depigmentation. Vitiligo can have a high quality-of-life burden and...
INTRODUCTION
Vitiligo is a chronic autoimmune disease characterized by destruction of melanocytes, leading to skin depigmentation. Vitiligo can have a high quality-of-life burden and profound impact on psychosocial well-being. The objectives of this study were to describe the self-reported patient burden among patients with nonsegmental vitiligo with ≤ 10% affected body surface area, summarize the physician-reported psychosocial and psychological impact of vitiligo on patient lives, and describe disease characteristics and treatment history, goals, and satisfaction.
METHODS
Data were drawn from the Adelphi Vitiligo Disease Specific Programme™, a real-world, cross-sectional survey with retrospective data collection of physicians and patients with vitiligo, collected in the United States between October 2021 and April 2022. Separate surveys for dermatologists and patients contained questions on clinical and demographic characteristics of patients with vitiligo and burden of vitiligo. Treatment history, goals, and satisfaction were assessed together with the impact of vitiligo on quality of life.
RESULTS
Sixty-one dermatologists provided data for 326 patients with ≤ 10% affected body surface area (adults, n = 221; adolescents, n = 105); 90 of those patients also responded to the survey. The most common treatments were topical corticosteroids, topical calcineurin inhibitors, and narrow-band ultraviolet-B phototherapy, with the main treatment goal being repigmentation. Physician-reported treatment satisfaction was 56%; 25% of patients reported frustration with treatment options. Physicians reported impact of vitiligo on everyday life in 46% of patients. Patients reported 12.7% overall work impairment; mean scores for Hospital Anxiety and Depression Scale anxiety and depression domains were 3.5 and 2.2, respectively, and mean Vitiligo-specific Quality of Life index score was 26.9. Patients with facial involvement experienced higher burden than those without.
CONCLUSION
A high patient burden was reported by dermatologists and their patients with vitiligo who had ≤ 10% affected body surface area, including psychosocial and psychological consequences. These findings highlight an unmet need in the treatment of vitiligo.
PubMed: 38753072
DOI: 10.1007/s13555-024-01165-5 -
Infection and Drug Resistance 2024Chronic Mucocutaneous Candidiasis (CMC) is a rare immunodeficiency disease characterized by chronic or recurrent superficial infections on the skin, nail, and mucous...
Chronic Mucocutaneous Candidiasis (CMC) is a rare immunodeficiency disease characterized by chronic or recurrent superficial infections on the skin, nail, and mucous membranes. Here, we present four Chinese patients with CMC who manifested oral mucosal leukoplakia and nail thickening during early childhood, all displaying fissured tongue lines. The causative pathogens isolated from their oral mucosa and nails were identified as and through morphology and molecular sequencing. Notably, among the four patients, one presented with vitiligo, while another had hypothyroidism. We have also conducted a review of reported cases of CMC in China and worldwide over the last five years, highlighting potential approaches for diagnosis and treatment. The current molecular evidence in the literature suggests potential for the development of early diagnosis methods, such as screening genetic variables on and . Additionally, potential treatment avenues, including gene-targeted analogues and GM-CSF analogues, could be explored in conjunction with traditional antifungal therapy.
PubMed: 38745679
DOI: 10.2147/IDR.S456121 -
Journal of Cutaneous and Aesthetic... 2024There are many instruments to prick the comedone before its extraction and scalp during hair transplantation. These instruments are not well guarded, and it can cause...
There are many instruments to prick the comedone before its extraction and scalp during hair transplantation. These instruments are not well guarded, and it can cause deep injury and fear in the patients. Here we described how to guard these needle for safety during procedure.
PubMed: 38736867
DOI: 10.4103/JCAS.JCAS_62_21 -
The Journal of Medical Investigation :... 2024Vitiligo is an acquired chronic depigmenting disorder of the skin and is characterized by the destruction of melanocytes. One of the clinical features of vitiligo is...
Vitiligo is an acquired chronic depigmenting disorder of the skin and is characterized by the destruction of melanocytes. One of the clinical features of vitiligo is that damage to normal skin frequently results in the formation of depigmented macules, which is known as Köebner's phenomenon (KP). Here, we presented a case of vitiligo, in which depigmented macules followed the course of a dilated varicose vein. Dilatation of blood vessels was considered to contribute to the development of the vitiliginous lesions as a trigger for KP. Any kind of skin injury can trigger KP, but this is only the second case in which a dilated blood vessel caused KP in vitiligo. J. Med. Invest. 71 : 177-178, February, 2024.
Topics: Humans; Vitiligo; Varicose Veins; Leg; Male; Female; Adult
PubMed: 38735717
DOI: 10.2152/jmi.71.177 -
Journal of Clinical Medicine May 2024There is currently no guidance on how to interpret the global degrees of activity (worsening) and repigmentation (improvement) in vitiligo. Stratification into global...
There is currently no guidance on how to interpret the global degrees of activity (worsening) and repigmentation (improvement) in vitiligo. Stratification into global degrees can be completed for static evaluations (e.g., visible disease activity signs) and dynamic assessments (e.g., evolution over time). For the latter, the Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS) were recently validated. : In the current study, a Physician Global Assessment (PGA) for disease activity (worsening) and repigmentation (improvement) was evaluated for validity (construct) and reliability (inter- and intrarater) based on a photo set of 66 patients. Subsequently, the PGA activity (worsening) and repigmentation (improvement) were used to stratify the Vitiligo Extent Score plus (VESplus), VDAS or VDIS into three global categories (slightly, moderately and much worse/improved), based on ROC analysis. : For the VESplus, cut-off values for the categories 'slightly, moderately and much worse' were >0.3%, >27.71% and >128.75% BSA (relative changes in the affected total BSA), respectively. For the categories 'slightly, moderately and much improved', they were >0%, >4.87% and >36.88% BSA (relative changes in the affected total BSA), respectively. The optimal cut-off values of the number of active (VDAS) body areas were >0 areas for slightly worse, >2 areas for moderately worse and >7 for much worse. For VDIS, the cut-off values for slightly improved and moderately improved were >0 and >1. For VDAS and VDIS, the cut-off points were >0.5, >3, >9.5 and >0.5 and >1.5, respectively. The results should be interpreted with caution in patients with extensive vitiligo due to the rather limited disease extent of the included patient population (VESplus (median: 3.2%)). : This research will aid in the development of more detailed international definitions.
PubMed: 38731208
DOI: 10.3390/jcm13092680 -
Dose-response : a Publication of... 2024Acute lung injury (ALI) is a serious illness that has few treatment options available. Tribuloside, a natural flavonoid extracted from the Tribulus Terrestris plant in...
BACKGROUND
Acute lung injury (ALI) is a serious illness that has few treatment options available. Tribuloside, a natural flavonoid extracted from the Tribulus Terrestris plant in China, is potent in addressing many health issues such as headaches, dizziness, itching, and vitiligo.
OBJECTIVE
This study intends to explore the mechanisms of action of Tribuloside in treating ALI through a combination of network pharmacology and experimental validation.
METHODS
We obtained the 2D structure and SMILES number of Tribuloside from the PubChem database. We used the SwissTargetPrediction database to identify pharmacological targets. We found 1215 targets linked to ALI by examining the GeneCards database. We used the String database and Cytoscape software to create the "drug or disease-target" network as well as the protein-protein interactions (PPI). Key targets were identified by evaluating associated biological processes and pathway enrichment. A Venny Diagram showed 49 intersection points between Tribuloside and ALI. Molecular docking with AutoDockTools found that Tribuloside had a high affinity for IL6, BCL2, TNF, STAT3, IL1B, and MAPK3, the top 6 targets in the PPI network by Degree values. To test Tribuloside's therapeutic efficacy in ALI, an acute lung damage model in mice was constructed using lipopolysaccharide. Tribuloside treatment reduced inflammatory cell infiltration, decreased fibrotic area, repaired damaged alveoli, and suppressed inflammatory factors IL-6, TNF-α, and IL-1β in the lungs through many pathways and targets.
CONCLUSION
This study reveals that Tribuloside has the potential to treat ALI by targeting various pathways and targets, according to network pharmacology predictions and experimental confirmation.
PubMed: 38725454
DOI: 10.1177/15593258241251594 -
Frontiers in Immunology 2024Vitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of...
INTRODUCTION
Vitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of white patches in the skin. The Smyth chicken is the only model for vitiligo that shares all the characteristics of the human condition including: spontaneous post-natal loss of epidermal melanocytes, interactions between genetic, environmental and immunological factors, and associations with other autoimmune diseases. In addition, an avian model for vitiligo has the added benefit of an easily accessible target tissue (a growing feather) that allows for the repeated sampling of an individual and thus the continuous monitoring of local immune responses over time.
METHODS
Using a combination of flow cytometry and gene expression analyses, we sought to gain a comprehensive understanding of the initiating events leading to expression of vitiligo in growing feathers by monitoring the infiltration of leukocytes and concurrent immunological activities in the target tissue beginning prior to visual onset and continuing throughout disease development.
RESULTS
Here, we document a sequence of immunologically significant events, including characteristic rises in infiltrating B and αβ T cells as well as evidence of active leukocyte recruitment and cell-mediated immune activities (CCL19, IFNG, GZMA) leading up to visual vitiligo onset. Examination of growing feathers from vitiligo-susceptible Brown line chickens revealed anti-inflammatory immune activities which may be responsible for preventing vitiligo (IL10, CTLA4, FOXP3). Furthermore, we detected positive correlations between infiltrating T cells and changes in their T cell receptor diversity supporting a T cell-specific immune response.
CONCLUSION
Collectively, these results further support the notion of cell-mediated immune destruction of epidermal melanocytes in the pulp of growing feathers and open new avenues of study in the vitiligo-prone Smyth and vitiligo-susceptible Brown line chickens.
Topics: Animals; Vitiligo; Chickens; Feathers; Disease Models, Animal; Melanocytes; T-Lymphocytes
PubMed: 38720888
DOI: 10.3389/fimmu.2024.1386727