Explore the vast range of titles available.

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. 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. 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. 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.

Vitiligo is a common dermatological disorder affecting 1–2% of the world’s population. It is characterized by postnatal, autoimmune destructions of melanocytes in the skin, resulting in patches of depigmentation. Autoimmunity in vitiligo may also affect melanocytes in non-integumental tissues, including the eyes where choroidal melanocytes are the target of the autoimmune response. The Smyth line (SL) of chicken is the only animal model that spontaneously and predictably develops all clinical and biological manifestations of autoimmune vitiligo. In SL vitiligo (SLV), destruction of epidermal melanocytes in growing feathers (GFs) involves a melanocyte-specific, Th1-mediated cellular immune response. Smyth chickens may also exhibit uveitis and vision impairment. Previous studies established a strong association between SLV and vision impairment, including similar pathology in affected eyes and GFs. To determine the presence, types, and activities of choroid infiltrating mononuclear cells, we collected eyes before, near onset, and during active SLV from sighted, partially blind, and blind SL chickens. All SL chickens with vision impairment had SLV. Immunohistochemistry and quantitative reverse transcriptase-PCR analyses revealed mononuclear cell and cytokine expression profiles in the autoimmune destruction of melanocytes in choroids that are identical to those described in GF, demonstrating the systemic nature of autoimmunity against melanocytes in SLV. In addition, we observed aberrant melanogenesis in SL eyes. The immunopathogenesis in SL vision impairment resembles human vitiligo-associated ocular diseases, especially Vogt–Koyanagi–Harada syndrome and sympathetic ophthalmia. Hence, the Smyth chicken autoimmune vitiligo model provides the opportunity to expand our understanding of spontaneous autoimmune pigmentation disorders and to develop effective treatment strategies.

Background : Recent clinical and animal experimental studies postulate that the pathogenetic mechanisms of vitiligo could be of systemic origin as vitiligo is associated with ocular and auditory abnormalities as well as other autoimmune disorders.Hence, we studied genetic factors, systemic associations, ocular and auditory abnormalities of vitiligo. Methods: The study group included 150 new cases of various types of vitiligo. One hundred age- and sex-matched nonvitiligo cases were included as controls in the study. A complete family history was taken for all patients. Examination was carried out taking note of the type of vitiligo and approximate percentage of body surface involved. All relevant laboratory investigations, a thorough audiological examination including pure tone audiometry and a complete ophthalmologic examination were carried out in all patients and controls. Statistical analysis was done using the Chi square test. Results: Fifty-four vitiligo patients (36%) had a family history of vitiligo. Anemia was present in 30 (20%) vitiligo patients but only in five (5%) controls, a difference that was statistically significant (χ 2 = 15.8, P < 0.001). Diabetes mellitus was present in 24 (16%) vitiligo patients and only 2 (2%) of controls (Chi square, χ2 = 12.4, P < 0.001). Hypothyroidism and alopecia areata were present in 18 (12%) and 11 (7.4%) vitiligo patients respectively and none of the controls. Hypoacusis was seen in 30 (20%) vitiligo patients and two (2%) controls (χ2 = 8.19, P < 0.005). Twenty-four vitiligo patients (16%) and five controls (5%) had specific ocular abnormalities like uveitis, iris and retinal pigmentary abnormalities (c2 = 7.39, P < 0.001). Conclusion: This study demonstrates statistically significant clinical evidence confirming that vitiligo is a part of systemic autoimmune process.

The occurrence of three or more autoimmune disorders in one patient defines multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is not known yet and environmental triggers and genetic susceptibility have been suggested to be involved. Herein, we report a 47-year-old woman who had Hashimoto’s thyroiditis, vitiligo and newly diagnosed ulcerative colitis. Diagnosis of ulcerative colitis was confirmed with histopathologic examination. This case presents a new combination of multiple autoimmune syndrome.

Although antibodies (Abs) produced by B cells can treat cancer in certain models, T cells have been accountable for the major effector to control cancer. Immune recognition toward tyrosinase-related protein-1 (TRP-1), a melanoma associated antigen up-regulated on the surface of B16F10 melanomas, generally leads to tumor protection mediated by Abs. In this study, immunization with dendritic cells ex vivo transduced with adenovirus encoding TRP-1 stimulates immune activation and potent tumor protection mediated by CD8 T cells in the absence of autoimmune consequence. Transfer of CD8 T cells from immunized mice also leads to tumor protection. The immune activation and CD8 T cell mediated tumor protection rely on the CD4 T cell help. Thus DC based genetic immunization targeting TRP-1, an antigen usually causes Ab predominant immune recognition, is capable of stimulating potent tumor protection dependent on CD8 T cells in the absence of autoimmunity.

Background: There is scarce published data on late onset vitiligo. All the studies showing association of audiological abnormalities have been done on younger age group of patients. Aim: To study the clinical characteristics of the patients with late onset vitiligo. Also, to investigate the audiological abnormalities seen in these patients and compare them with age and sex matched healthy volunteers. Methods: One hundred and ninety-seven consecutive patients developing vitiligo after the age of 40 were studied. These patients were examined for the audiological abnormalities, and compared with those seen in age and sex matched healthy volunteers. Results: Vitiligo started between 40 and 50 years of age in 68.02% of our patients. Vitiligo vulgaris was the commonest clinical pattern, and most patients reported onset of their vitiligo on the upper extremities. Fifty four had diabetes mellitus, 19 patients had autoimmune thyroid diseases, and 32 showed hypoacusis on audiometric examination. Eighteen controls (age and sex matched healthy volunteers) also showed hypoacusis. The difference in frequency was not significant (22.37% vs 18%, Χ2- test, P > 0.05). The sensorineural type of audiologic impairment was more commonly seen both in patients as well as in controls. Conclusion: Late onset vitiligo was not found to have statistically significant association with audiological abnormalities in this study.

Vitiligo reflects a systemic process that has important implications beyond the skin. These include other autoimmune diseases and ocular and neurological abnormalities. Alezzandrini syndrome and Vogt-Koyanagi-Harada syndrome particularly exemplify this relationship. In addition, vitiligo may be confused with other systemic disorders, including tuberous sclerosis, progressive systemic sclerosis (scleroderma), melanoma, and, in endemic regions, leprosy. We describe these associations and emphasize the importance of depigmenting disorders.

The skin serves as a physical barrier and an immunological interface that protects the body from the external environment 1 – 3 . Aberrant activation of immune cells can induce common skin autoimmune diseases such as vitiligo, which are often characterized by bilateral symmetric lesions in certain anatomic regions of the body 4 – 6 . Understanding what orchestrates the activities of cutaneous immune cells at an organ level is necessary for the treatment of autoimmune diseases. Here we identify subsets of dermal fibroblasts that are responsible for driving patterned autoimmune activity, by using a robust mouse model of vitiligo that is based on the activation of endogenous auto-reactive CD8 + T cells that target epidermal melanocytes. Using a combination of single-cell analysis of skin samples from patients with vitiligo, cell-type-specific genetic knockouts and engraftment experiments, we find that among multiple interferon-γ (IFNγ)-responsive cell types in vitiligo-affected skin, dermal fibroblasts are uniquely required to recruit and activate CD8 + cytotoxic T cells through secreted chemokines. Anatomically distinct human dermal fibroblasts exhibit intrinsic differences in the expression of chemokines in response to IFNγ. In mouse models of vitiligo, regional IFNγ-resistant fibroblasts determine the autoimmune pattern of depigmentation in the skin. Our study identifies anatomically distinct fibroblasts with permissive or repressive IFNγ responses as the key determinant of body-level patterns of lesions in vitiligo, and highlights mesenchymal subpopulations as therapeutic targets for treating autoimmune diseases. Single-cell analyses of skin samples from patients with vitiligo and functional genetic experiments in vitiligo mouse models show that distinct fibroblast subsets drive the organ level lesion patterns in this autoimmune disease.

Vitiligo is an autoimmune disease that has been recognized, stigmatized, and treated for millennia. Recent translational research has revealed key mechanisms of disease, including cellular stress, innate immune activation, T cell-mediated elimination of melanocytes from the skin resulting in clinically apparent white spots, as well as stem cell regeneration that reverses established lesions. Many of these pathways have been targeted therapeutically, leading to the first FDA-approved medication to reverse the disease, with many more in clinical trials. Despite these impressive advances, many questions remain, which will be answered through integration of additional basic, translational, and clinical research studies. This vitiligo revolution has led to great excitement for individuals with vitiligo, those who know them, and the dermatologists who care for their patients. But just as importantly, these advances have great potential to shed light on autoimmune diseases that are more difficult to study, possibly leading to treatment advances that could not be achieved otherwise.

Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo. We conducted two phase 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation in Vitiligo Study 1 [TRuE-V1] and 2 [TRuE-V2]) in North America and Europe that involved patients 12 years of age or older who had nonsegmental vitiligo with depigmentation covering 10% or less of total body-surface area. Patients were randomly assigned in a 2:1 ratio to apply 1.5% ruxolitinib cream or vehicle control twice daily for 24 weeks to all vitiligo areas on the face and body, after which all patients could apply 1.5% ruxolitinib cream through week 52. The primary end point was a decrease (improvement) of at least 75% from baseline in the facial Vitiligo Area Scoring Index (F-VASI; range, 0 to 3, with higher scores indicating a greater area of facial depigmentation), or F-VASI75 response, at week 24. There were five key secondary end points, including improved responses on the Vitiligo Noticeability Scale. A total of 674 patients were enrolled, 330 in TRuE-V1 and 344 in TRuE-V2. In TRuE-V1, the percentage of patients with an F-VASI75 response at week 24 was 29.8% in the ruxolitinib-cream group and 7.4% in the vehicle group (relative risk, 4.0; 95% confidence interval [CI], 1.9 to 8.4; P<0.001). In TRuE-V2, the percentages were 30.9% and 11.4%, respectively (relative risk, 2.7; 95% CI, 1.5 to 4.9; P<0.001). The results for key secondary end points showed superiority of ruxolitinib cream over vehicle control. Among patients who applied ruxolitinib cream throughout 52 weeks, adverse events occurred in 54.8% in TRuE-V1 and 62.3% in TRuE-V2; the most common adverse events were application-site acne (6.3% and 6.6%, respectively), nasopharyngitis (5.4% and 6.1%), and application-site pruritus (5.4% and 5.3%). In two phase 3 trials, application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks, but it was associated with acne and pruritus at the application site. Larger and longer trials are required to determine the effect and safety of ruxolitinib cream in patients with vitiligo. (Funded by Incyte; TRuE-V1 and TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 and NCT04057573.).