Psoriasis Regression Analysis of MHC Loci Identifies Shared Genetic Variants with Vitiligo

Zhu, Kunju; Lv, Yong Mei; Xian, Yin; Wang, Zai Xing; Sun, Liang; He, Shuangba; Cheng, Hui; Hu, Da Yan; Zhang, Zheng; Li, Yang; Zuo, Xian Bo; Zhou, You; Yang, Sen; Fan, Xing; Zhang, Xue Jun; Zhang, Fengyu

doi:10.1371/journal.pone.0023089

Cited by 50 publications

(45 citation statements)

References 48 publications

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“…There is evidence that vitiligo is an autoimmune disease [6], [7], [8], [9], [10], [11], [12], [13], [14], possibly involving additional factors such as oxidative stress [15] and genetic predisposition [6], [10], [11], [12], [13], [16], [17], [18]. The autoimmune hypothesis stems from the frequently observed association with other autoimmune diseases, such as hypothyroidism and diabetes [19], [20], [21], [22], [23].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

Broady

Huang

et al. 2012

PLoS ONE

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BackgroundVitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients.Methods and MaterialsPaired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy.ResultsCompared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients.Conclusions and Clinical ImplicationsAs the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting the entire skin surface may improve treatment outcomes. Finally, this study revealed novel mediators that may facilitate future development of vitiligo therapies.

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Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

Broady

Huang

et al. 2012

PLoS ONE

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“…This association appears to be more common in Caucasian and Hispanic/Latino patients. Zhu et al [12] recently identified loci in the MHC region that are associated with both psoriasis and vitiligo. Further work investigating this association may prove useful in improving our understanding of the pathogenesis of vitiligo.…”

Section: Discussionmentioning

confidence: 99%

Comorbidities Associated with Vitiligo: A Ten-Year Retrospective Study

Sheth¹,

Guo²,

Qureshi³

2013

Dermatology

106

102

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Background: Vitiligo is a common disorder of depigmentation that has been associated with other autoimmune diseases. No recent large-scale data exist on the rates of comorbidities associated with vitiligo from the United States population. Objectives: To identify the prevalence of comorbidities as well as associated laboratory abnormalities in vitiligo patients. Methods: All medical records dating from January 1, 2000 to June 21, 2011 within the Research Patient Data Repository were evaluated retrospectively using a novel artificial intelligence-based computer program. A total of 3,280 patients carrying the diagnosis of vitiligo were identified using ICD-9 code 709.01. We randomly selected 300 patients and validated the diagnosis by manually reviewing their medical records. These results were used to create a model that was then applied to the larger set yielding 2,441 true vitiligo patients. 1,657 (68%) were diagnosed by dermatologists and 784 (32%) by non-dermatologists. We identified the prevalence of other comorbid autoimmune conditions by searching problem lists of vitiligo patients and collected laboratory data from the first available data point in the system for each patient. Results: Women were more frequently represented (57.6%) than men (42.4%). The majority of vitiligo patients were White/Caucasian (56.9%), followed by Hispanic/Latino (19.4%). 565 (23%) had one of the following comorbidities: 287 thyroid-related, 186 psoriasis, 72 rheumatoid arthritis, 59 alopecia areata, 55 inflammatory bowel disease, 53 systemic lupus and 20 type I diabetes mellitus. 41% had elevated anti-nuclear antibody levels. Almost half of the patients tested had elevated thyroid peroxidase antibodies. Over 50% of the patients tested had low or insufficient levels of 25-OH vitamin D. Conclusion: We found a high prevalence of comorbidities among individuals with vitiligo presenting to teaching hospitals in Boston, Mass. Comorbid autoimmune conditions were seen in 23% of vitiligo patients, thyroid disorders and psoriasis being the most common. Screening for these conditions, especially thyroid disorders, should be considered in vitiligo patients.

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“…This is supported by our statistically significant result that more patients with psoriasis and vitiligo used drugs that induced psoriasis when compared with vitiligo patients alone. This datum does have certain limitations in that we did not perform HLA studies associated with an increased genetic risk of psoriasis . We can further not be entirely sure that patients remember or report drugs they have consumed and can therefore not exclude that a recall bias accounts for this difference.…”

Section: Discussionmentioning

confidence: 97%

Non‐segmental vitiligo and psoriasis comorbidity – a case‐control study in Italian patients

Arunachalam

Dragoni

Colucci

et al. 2013

Acad Dermatol Venereol

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Psoriasis Regression Analysis of MHC Loci Identifies Shared Genetic Variants with Vitiligo

Cited by 50 publications

References 48 publications

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

Comorbidities Associated with Vitiligo: A Ten-Year Retrospective Study

Non‐segmental vitiligo and psoriasis comorbidity – a case‐control study in Italian patients

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