The angiotensin‐converting enzyme gene insertion/deletion polymorphism in Indian patients with vitiligo: a case–control study and meta‐analysis

Background  Vitiligo is a common, acquired, idiopathic depigmenting skin disorder. Although the exact pathogenesis remains unknown, genetic susceptibility and autoimmune responses play a role in vitiligo development. Previous studies have suggested that the D allele of the insertion/deletion (I/D) polymorphism of the angiotensin‐converting enzyme (ACE) gene is associated with vitiligo in Indians and Koreans. Furthermore, significantly higher serum ACE levels have been demonstrated in patients with some autoimmune and autoinflammatory disorders. Objectives  The objectives were to investigate any association between the ACE I/D polymorphism and vitiligo susceptibility in an Indian population, and to compare serum ACE levels in patients with vitiligo and healthy subjects. Methods  The ACE I/D genotypes of 79 patients with vitiligo and 100 normal individuals were determined by polymerase chain reaction amplification. A meta‐analysis was done to compare the distribution of the ACE I/D alleles and genotypes in the current and three previous studies. Serum ACE levels were evaluated by enzyme‐linked immunosorbent assay. Results  A significant increase in the frequency of the ACE I/D D allele was evident in patients with vitiligo in both the case–control study [P = 0·005; odds ratio (OR) 1·87; 95% confidence intervals (CI) 1·22–2·85] and the meta‐analysis (P = 0·044; OR 1·44; 95% CI 1·01–2·06). Serum ACE levels were significantly increased in patients with vitiligo compared with healthy subjects (P < 0·0001). Conclusions  In agreement with earlier reports, the ACE I/D D allele is associated with vitiligo susceptibility in the Indian population. The significantly elevated serum ACE levels in our cohort of patients with vitiligo concur with those previously found in patients with some other autoimmune diseases.     

Increased level of cathelicidin (LL-37) in vitiligo: Possible pathway independent from vitamin D receptor gene polymorphism

Vitiligo is a multifactorial skin disease with established role of genetics and autoimmunity in its pathogenesis. Vitamin D receptor (VDR) polymorphisms have been suggested to correlate with risk of vitiligo in some ethnic populations. On the other hand, cathelicidin, one of the innate immune system components, has a role in development of some chronic skin diseases and VDR regulates the expression of cathelicidin. We aimed to determine the plasma level of cathelicidin and its association with the VDR gene polymorphisms as well as plasma vitamin D level in patients with vitiligo. Ninety vitiligo patients and 90 non-vitiligo controls participated in this study. Blood levels of 25(OH) vitamin D and cathelicidin were determined with ELISA. Genotyping for VDR polymorphisms (ApaI, TaqI, FokI and BsmI) was done with RFLP-PCR method. Mean blood level of cathelicidin was significantly higher in vitiligo patients as compared to controls (P < .0001). Mean blood level of vitamin D was significantly lower in patients than controls (P = .01). Statistically significant differences were not observed for both genotype and allele frequencies of BsmI, ApaI and TaqI polymorphisms. There was a borderline increased risk of vitiligo in over-dominant model of FokI polymorphism with OR = 1.8 and P = .051. Our findings was suggestive of the potential role of cathelicidin in the pathogenesis of vitiligo; however, future evaluations are needed to determine its precise mechanism. Genetic study of VDR gene polymorphism was suggestive of increased risk of vitiligo in association with a FokI polymorphism in Iranian population.     

Possible association of the CD4 gene polymorphism with vitiligo in an Iranian population

Background. Vitiligo is an acquired idiopathic and polygenic disorder with progressive depigmentation of circumscribed patches. Its exact pathogenesis is unknown. The CD4 gene plays an important role in the cell‐mediated immune response and its association with type 1 diabetes mellitus, which is an autoimmune disease, has been previously reported. Methods. Based on the assumption that autoimmunity is also involved in vitiligo, the CD4 gene was selected for study using a candidate gene approach. The pyrimidine‐rich pentanucleotide repeat length polymorphism located in the promoter of the gene was studied. We screened 144 unrelated Iranian patients with vitiligo and 144 healthy matched controls by PCR. Results. The CD4*A4 allele has a susceptibility association with the development of vitiligo in the Iranian population (OR = 1.68, 95% CI 1.18–2.42; P < 0.01, P_c = 0.02). When we compared CD4*A4‐containing genotypes in the case and control groups, even more significant positive association was identified (OR = 2.02, 95% CI 1.26–3.22; P < 0.01 and P_c < 0.01). The CD4 gene polymorphism has a modest association with the development of vitiligo in Iranian patients.     

Clinical Analysis of Thyroglobulin Antibody and Thyroid Peroxidase Antibody and their Association with Vitiligo

Background:

Recently, the abnormal presence of thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) has been reported in vitiligo patients, but presence of TG-Ab and TPO-Ab in patients of different ages and gender, and its association with vitiligo and thyroid autoimmunity has rarely been reported. The aim of our research was to determine whether vitiligo was associated with thyroid autoimmunity and figure out its relationship with age and gender.

Materials and Methods:

We analyzed TG-Ab, TPO-Ab in age and gender matched 87 vitiligo patients and 90 healthy controls, the patients of vitiligo who were positive for the presence of TG-Ab and TPO-Ab were followed up to confirm autoimmune thyroid disease subsequently.

Results:

Results showed that the frequencies of TG-Ab (23.0%, 20/87) positivity and TPO-AB (24.1%, 21/87) in vitiligo patients were significantly higher than that in healthy controls (P < 0.05). Moreover, The positivity for of TG-Ab and TPO-Ab was higher in 11-20-year age group and 21-40-year age group than that in age matched healthy controls. We found female patients with vitiligo had higher positive frequencies of TG-Ab and TPO-Ab than healthy female controls. (34.1% vs. 8.8% and 34.1% vs. 11.1%, P = 0.000 and P = 0.011). When 20 patients with TG-Ab and TPO-Ab positivity were followed up for three monthes, 14 of them (70%) were diagnosed as having autoimmune thyroid disease compared with age-matched healthy controls (16.7%, χ² = 5.4, P = 0.02).

Conclusion:

TG-Ab and TPO-Ab are likely to be found in female teenagers with vitiligo, and are relevant with respect to subsequent development autoimmune thyroid disease.     

Role of interleukin-17 in the pathogenesis of vitiligo

Background. Skewing of the immune response towards T helper (Th)1 or Th17 and away from regulatory T cells (Tregs) and Th2 cells may be responsible for the development and progression of autoimmune disease. An autoimmune theory has been proposed in the pathogenesis of vitiligo. No previous reports have investigated alterations in IL‐17 produced by Th17 cells in lesional skin in vitiligo. Aim. To investigate the role of IL‐17 in the pathogenesis of vitiligo by assessing its levels in lesional skin and serum of patients with vitiligo compared with controls. Methods. In total, 30 patients with vitiligo and 20 controls matched for age and gender were enrolled in the study. Serum and tissue IL‐17 levels were measured by ELISA and compared between both groups for correlations with age, gender, family history, disease duration, activity of vitiligo and percentage of involved body surface area. Results. A significant difference between patients and healthy controls was found for both serum and tissue IL‐17 levels (P < 0.001 for both). Significant positive correlations were found between disease duration and IL‐17 level in both serum (r = 0.42, P = 0.02) and lesional skin (r = 0.45, P < 0.015); between extent of vitiligo and IL‐17 levels in both serum (r = 0.65, P < 0.001) and skin (r = 0.48, P < 0.05); and between the serum and the tissue IL‐17 levels in patients with vitiligo (r = 0.54, P = 0.002). Conclusions. Multiple factors have been implicated in the pathogenesis of vitiligo. The increased levels of IL‐17 we found in serum and lesional skin suggest an important role for this cytokine in the pathogenesis of vitiligo.     

Angiotensin converting enzyme (ACE) gene polymorphism in vitiligo: protective and predisposing effects of genotypes in disease susceptibility and progression

Vitiligo is a depigmenting skin disorder with profound heterogenity in its aetio-pathophysiology, and is associated with inter-individual variation in progression of disease. Angiotensin converting enzyme (ACE) is a regulator of renin angiotensin system (RAS) that plays an important role in the physiology of the vasculature, blood pressure, inflammation, adipocyte distribution of various diseases. The present study was carried out in 243 vitiligo patients (132 males and 111 females), aged between 3-62 years with a mean age at onset of 21.6 ± 13.6 yrs, and in 205 healthy controls of south Indian origin. The main objectives of the present study were to evaluate the ACE I/D (insertion/deletion) polymorphism in the patient and control groups. Further, I/D genotypes were compared among the patients with and without the family history of vitiligo as well as the progression of the disease, through polymerase chain reaction (PCR) methods.

The results revealed a highly significant association of DD genotype with disease susceptibility (p?相似文献   

Relevance of autoimmune thyroiditis in children and adolescents with vitiligo

Background Vitiligo is the most common pigmentation‐related disorder worldwide. An autoimmune etiology is widely considered, and genetic factors may play an important role in its pathogenesis. The purpose of this study was to assess the incidence of thyroid dysfunctions and autoimmune thyroiditis in children with vitiligo and to identify related factors. Methods Fifty children with vitiligo and 50 control children were enrolled. Data on age, onset, duration, disease activity, presence of thyroid disorder, other autoimmune diseases, halo nevi, poliosis, and mucosal vitiligo were determined. Serum free triiodothyronine, free thyroxine, total T3, total T4, thyroid‐stimulating hormone, and antibodies to thyroperoxidase and thyroglobulin were measured. Thyroid gland efficiency was evaluated. Results The mean age at onset of vitiligo was 7.26 ± 4.43 years. The duration of vitiligo was 2.26 ± 2.95 years. Vulgaris‐type vitiligo was the most common form in our patients (56%), and 42% reported at least one family member with thyroid disorder, autoimmune disease, or both. Overt hypothyroidism or hyperthyroidism were not detected. We found a significant association between autoimmune thyroiditis and both sex and disease duration (P = 0.046 and P = 0.07, respectively), but no association between autoimmune thyroiditis and age, age at onset of vitiligo, halo nevi, poliosis, mucosal involvement, disease activity, or family history of vitiligo, autoimmunity, or thyroid disorders. Conclusions Children with vitiligo show an increased incidence of autoimmune thyroiditis. Children with vitiligo, especially girls and subjects with generalized/vulgaris‐type vitiligo, should be screened annually for thyroid function and antithyroid antibodies to assist in the early diagnosis and therapy of autoimmune thyroiditis.     

An approach to the correlation between vitiligo and autoimmune thyroiditis in Chinese children

Background. Vitiligo is a common skin depigmenting disease, which is thought to have, at least partly, an autoimmune aetiology. Aim. To explore the correlation between paediatric vitiligo and other associated diseases, with an emphasis on autoimmune thyroiditis (AT). Methods. In total, 363 paediatric patients (198 boys, 165 girls) with vitiligo and 93 healthy children (55 boys, 38 girls) were screened for autoimmune thyroiditis. The two groups were matched for age and gender. Children with vitiligo were split into two groups according to type (segmental and nonsegmental vitiligo). Demographic data, clinical features and examinations were recorded using questionnaires. Thyroid function tests including free triiodothyronine, free thyroxine and thyroid‐stimulating hormone were performed. Anti‐thyroid peroxidase antibody) and anti‐thyroglobulin antibody levels were assessed as well. Other associated diseases were also monitored in this study. Results. Of the 363 patients, 43 (11.8%) had abnormal levels of studied thyroid parameters, compared with 4 of the 93 controls (4.3%); the difference was significant (P = 0.04). The alterations of thyroid parameters and the incidence of AT in patients with nonsegmental vitiligo were both significantly different (P < 0.05, P = 0.04) relative to the segmental vitiligo group. Of the 363 patients, 67 (18.5%) had other associated diseases. There were no differences in the rates of other associated diseases between patients with segmental vitiligo and those with nonsegmental vitiligo (P > 0.05). Conclusions. A significant incidence of thyroid dysfunction was found in paediatric patients with nonsegmental vitiligo. As vitiligo usually appears before the development of the thyroid disease, it may be advantageous to screen thyroid functions and antibody levels in all paediatric patients with vitiligo, especially those with nonsegmental vitiligo.     

Association of ACE gene I/D polymorphism with vitiligo: a meta-analysis

Associations of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) functional single-nucleotide polymorphisms (SNPs) with vitiligo have been reported, but the results were inconsistent. To investigate the association of SNPs in the intron 16 of ACE gene with vitiligo susceptibility by the meta-analysis, case-control studies were conducted by searching from PubMed, HighWire and China National Knowledge Infrastructure as of May 2011. A total of 6 studies with 828 patients and 1,215 controls was finally identified. All control samples were in Hardy–Weinberg equilibrium. According to the clinical typing, the data were divided into pooled subgroup and generalized subgroup. Our meta-analysis showed that a significantly increased vitiligo risk was associated with the D/D genotype compared with the I/I + I/D genotype (Odds ratio (OR) 1.79, 95 % confidence interval (95 % CI) 1.35–2.38, P < 0.0001) and the D allele compared with the I allele (OR 1.72, 95 % CI 1.45–2.04, P < 0.00001) in pooled subgroup. In summary, this meta-analysis demonstrated that ACE D/D homozygote and D allele were significantly associated with an increased risk of vitiligo in pooled population. The results indicated that the people with ACE D/D homozygote and D allele may suffer from vitiligo, but of a generalized type. ACE polymorphism might be used as biomarkers for vitiligo risk prediction for pooled vitiligo.     

Vitiligo expansion and extent correlate with durable response in anti-programmed death 1 antibody treatment for advanced melanoma: A multi-institutional retrospective study

Vitiligo is an autoimmune disorder resulting from the destruction of melanocytes. Several reports indicate the association between vitiligo and treatment response in advanced melanoma during immunotherapy. It has not been investigated, however, if an increase of vitiligo while on treatment with anti-programmed death 1 (PD-1) antibodies is associated with more durable responses. The aim of this study is to evaluate the correlation between the vitiligo dynamics and clinical efficacy of anti-PD-1 antibodies. This study included advanced melanoma patients who were treated with nivolumab or pembrolizumab and developed vitiligo thereafter. Correlation between vitiligo expansion (defined as an increase of lesion size at two separate time points at least 4 weeks apart) as well as vitiligo extent (body surface area [BSA] affected) and clinical efficacy based on response rate, progression-free survival and overall survival was assessed. We retrospectively reviewed 29 patients. The median time from the initiation of anti-PD-1 antibody to vitiligo onset was 4.3 months in patients who showed a response and 5.5 months in patients who showed no response (P = 0.31). Twelve patients showed vitiligo expansion, and in nine of these patients, vitiligo increased to grade 2 (covering ≥ 10% BSA). Vitiligo expansion and grade 2 vitiligo showed no improvement in treatment response (P = 0.59 and 0.25) but were associated with prolonged progression-free survival (P = 0.019 and 0.04). Grade 2 vitiligo also showed a trend for prolonged overall survival (P = 0.07). Trend of expansion and larger vitiligo extent may be predictive factors of prolonged survival during anti-PD-1 antibody in melanoma patients.     

Serum brain-derived neurotrophic factor and vitamin D: Two concordant players controlling depression among alopecia areata and vitiligo patients: A case–control study

Background

Depression is a common psychiatric comorbidity among chronic dermatology patients. There is extreme lacking in the research studying biomarkers responsible for it. Both brain-derived neurotrophic factor (BDNF) and vitamin D have a significant role in the development of depression.

Aim

To assess BDNF and vitamin D serum levels in different clinical verities of alopecia areata (AA) and vitiligo patients, correlating them with depression prevalence and quality of life.

Methods

In all, 30 AA patients, 30 vitiligo patients, and 30 healthy volunteers were included. Both alopecia and vitiligo severity and activity were evaluated using the suitable clinical scores. Depression was assessed using Beck depression inventory (BDI) scale and quality of life was recorded using Dermatology Life Quality Index (DLQI). Both serum BDNF and vitamin D levels were investigated using ELISA.

Results

In both alopecia and vitiligo patients, serum BDNF and serum vitamin D were significantly lower compared to controls (p = 0.001 for both). Both were associated and negatively correlated with BDI and DLQI. Regarding alopecia, they showed a significant decline in more sever disease and with longer disease duration. However, in vitiligo, BDNF (p = 0.001) and vitamin D (p = 0.03) correlated negatively with disease activity, but not with disease severity. Serum BDNF and vitamin D correlated positively with each other (p = 0.001) in both AA and vitiligo cases.

Conclusion

The inverse association of both serum BDNF and vitamin D with depression, and the positive correlation noted between their serum levels, may indicate a potential combined effect of these two players on development of depression and its negative health-related outcomes.     

白癜风发病与自身免疫性甲状腺病的相关性探讨

目的探讨白癜风与自身免疫性甲状腺病(AITD)的发生是否存在相关性。方法用化学发光分析法测定38例白癜风患者和35名正常人群的甲状腺功能(包括抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体),比较白癜风患者和正常对照组间甲状腺自身抗体阳性率,同时比较甲状腺自身抗体阳性的白癜风患者与甲状腺自身抗体阴性的白癜风患者间AITD患病率。结果白癜风患者T3和T4与正常对照组比较差异无显著性(P>0.05),而白癜风患者FT3和FT4与正常对照组比较差异均有显著性(P<0.05)。白癜风患者血清TSH与正常对照组比较差异有显著性(P<0.01)。白癜风患者甲状腺自身抗体阳性率与正常对照组比较均有增高趋势(P<0.05)。甲状腺自身抗体阳性的白癜风患者AITD患病率(41.18%)与甲状腺自身抗体阴性的白癜风患者(9.52%)间比较明显增高(P<0.05)。结论白癜风的发病与甲状腺功能的改变和自身免疫有着密切的联系。     

Effects of age of onset on disease characteristics in non‐segmental vitiligo

In patients with vitiligo, the clinical and laboratory features of the disease may vary according to time of onset. This is addressed in the literature by only a few studies with conflicting results. The aim of this study was to determine the demographic and clinical features of patients with non‐segmental vitiligo and to establish the association between vitiligo and autoimmune diseases with a focus on time of disease onset. A total of 224 vitiligo patients for whom complete medical records were available were evaluated retrospectively. Demographic data, scores on the Vitiligo Area Score Index (VASI), clinical features, vitiligo disease activity, repigmentation status, presence of any accompanying autoimmune disease, antinuclear antibody (ANA) titers, serum levels of glucose, thyroid‐stimulating hormone (TSH), thyroxine (T4) hormone, anti‐thyroid peroxidase (anti‐TPO), and anti‐thyroglobulin (anti‐TG) were recorded. The prevalence of halo nevi was significantly higher (P < 0.001) among children than in other patient groups. The prevalence of leukotrichia was higher in adults with adult‐onset disease than in either pediatric patients or adults with childhood‐onset disease (P = 0.002). Both anti‐TG and anti‐TPO levels were significantly higher in adults with adult‐onset disease than in pediatric patients and adult patients with childhood‐onset disease. The prevalence of autoimmune disease was 22.2%. Anti‐TG levels were significantly higher in patients with treatment‐related repigmentation than in those without repigmentation. This study shows that clinical features and associations with autoimmune disease may vary according to the age of onset of vitiligo.     

Association of insertion/deletion polymorphism of the angiotensin-converting enzyme gene with angio-oedema accompanying chronic urticaria but not chronic urticaria without angio-oedema or the autologous serum skin test response

Background Chronic urticaria is defined as the daily or almost daily occurrence of weals for more than 6 weeks. The underlying pathophysiology is reported to be mast cell activation, with release of mast cell mediators, predominantly histamine. Substance P is a neuropeptide and has the capacity to provoke histamine release from skin mast cells. Angiotensin‐converting enzyme (ACE), widely expressed in skin, is one of the major peptidase for the degradation of substance P. An insertion/deletion polymorphism (I/D) in the ACE gene has been reported to be related to the levels of enzyme. Objective An increase in substance P levels due to a polymorphism in ACE gene might be related to the pathology. Thus, we aimed to investigate whether there is an association between ACE I/D polymorphism and chronic ordinary urticaria. Methods Ninety‐five patients with chronic ordinary urticaria were recruited and divided into two groups according to autologous serum skin test status and accompanying angio‐oedema. One hundred and sixty‐one healthy subjects were enrolled as control group. All participants were genotyped for I/D polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Results A statistically significant association was not found between ACE I/D polymorphism and chronic ordinary urticaria. Further analyses of chronic ordinary urticaria patients showed that ACE I/D polymorphism was not associated with autologous serum skin test status of patients. However, the frequencies of II genotype and I allele were statistically significantly higher in chronic ordinary urticaria patients with accompanying angio‐oedema with regard to angio‐oedema‐negative patients (II genotype: 24% vs. 9%, P = 0.0002; I allele: 58% vs. 27%, P = 0.0001) and control group (II genotype: 24% vs. 19%, P = 0.01; I allele: 58% vs. 41%, P = 0.03). Conclusion The results of this study suggest no evidence of an association between ACE I/D polymorphism and risk of developing chronic ordinary urticaria. However, it can be a contributing factor to susceptibility of angio‐oedema in chronic ordinary urticaria.     

Prognostic value and clinical significance of halo naevi regarding vitiligo

Background Vitiligo and halo naevi can present together or separately. Whether they are different entities remains unclear. Objectives To assess the clinical significance of halo naevi, both with respect to the future development of vitiligo, and to the clinical profile and course of vitiligo. Methods In total, 291 patients were included in this study: patients with only halo naevi (group 1; n = 40), patients with generalized vitiligo without halo naevi (group 2; n = 173) and patients with generalized vitiligo with halo naevi (group 3; n = 78). Results Patients with only halo naevi (group 1) reported significantly less associated autoimmune disease (P = 0·001), were less likely to have a family history of vitiligo (P = 0·013) and were less likely to have presence of Koebner phenomenon (P < 0·001) compared with patients with generalized vitiligo (groups 2 + 3). Multiple halo naevi (≥ 3) were significantly more frequently observed (P = 0·002) in patients from group 1 compared with patients from group 3. In group 3, halo naevi were reported prior to the development of vitiligo in 61% (mean ± SD time interval of 33·7 ± 5·17 months). No significant correlation was observed between the presence of halo naevi and the extent, activity or subtype of vitiligo. However, halo naevi in patients with vitiligo significantly reduced the risk for associated autoimmune diseases, and age at onset of vitiligo was significantly lower compared with patients with vitiligo without halo naevi (P < 0·001). Conclusions Our results support the hypothesis that halo naevi can represent a distinct condition. In a subset of patients, the occurrence of halo naevi may be an initiating factor in the pathogenesis of vitiligo.     

Vitiligo in children and adolescents: association with thyroid dysfunction

Background The clinical characteristics of vitiligo in children and adolescents with an emphasis on thyroid dysfunction have only been reported in a few studies. Objective The purpose of this study was to examine the characteristics of children and adolescents with vitiligo and compare the incidence of thyroid dysfunction between them and controls without vitiligo at the same age. Methods A retrospective analysis of 324 Korean children and adolescents with vitiligo was performed. The results of thyroid function screening tests in them (n = 254) were compared with controls (n = 122). Results Of the total 324 children and adolescents with vitiligo, vitiligo vulgaris was the most common type (42.3%) and the most commonly involved site was the face (54.6%). A total of 15 of 254 (5.9%) patients screened for thyroid function were diagnosed with thyroid disease (four had Hashimoto’s thyroiditis; two, Graves’ disease; seven, subclinical hypothyroidism; and two, subclinical hyperthyroidism). None of the 50 patients with segmental vitiligo showed any thyroid dysfunction (P = 0.047). There was no significant difference in the incidence of thyroid disease between children and adolescents with vitiligo and the control group, in which seven of 122 (5.7%) showed thyroid dysfunction. Conclusion In this study, we demonstrated the characteristics of children and adolescents with vitiligo and also observed no significant difference in the incidence of thyroid disease between children and adolescents with vitiligo and the control group.     

Macrophage migration inhibitory factor in patients with vitiligo and relationship between duration and clinical type of disease

Background. Vitiligo is a disorder of pigmentation characterized by the presence of depigmented skin macules. Cellular immunity is known to have a role in the pathogenesis of vitiligo. Macrophage migration inhibitory factor (MIF) is a potent activator of macrophages and is considered to play an important role in cell‐mediated immunity. Aims. To determine serum level of MIF in patients with vitiligo and compare with healthy controls. We also aimed to determine whether there is a relationship between MIF levels and the disease duration, clinical vitiligo and involved body surface area (BSA) in patients with vitiligo. Methods. The study group comprised 30 patients with vitiligo (14 men, 16 women) and 30 healthy controls, matched for age and gender. Blood samples were taken for MIF analysis. Results. The mean serum level of MIF in patients with vitiligo (40.83 ± 31.66 pg/mL) was significantly higher than that of the control group (21.00 ± 6.48 pg/mL) (P = 0.002). There was a positive correlation between disease duration and MIF levels (r = 0.601, P < 0.001). Mean MIF level of patients with acral and acrofacial vitiligo (n = 6) was 48.25 ± 32.02 pg/mL, and of patients generalized vitiligo (n = 18) was 44.46 ± 35.25 pg/mL. There was no significant difference between these two groups (P > 0.05). However there was a significant difference in MIF levels between patients with localized (20.41 ± 5.23, n = 5) and acral–acrofacial (P = 0.02) vitiligo and those with generalized (P = 0.006) vitiligo. There was no relationship between BSA and MIF levels. Conclusions. Mean serum MIF level of patients with vitiligo was higher than that of controls, indicating that MIF has a role in the pathogenesis of vitiligo.     

Association study between vitiligo and autoimmune-related genes CYP27B1, REL,TNFAIP3, IL2 and IL21

The aetiology of vitiligo has not been fully elucidated, and several hypotheses have been investigated; among them, the most explored assumes an autoimmune basis for the disease. Supporting this hypothesis is the frequent co-occurrence of autoimmune diseases with vitiligo. In addition, various genetic loci associated with vitiligo harbour key immune response genes. Our general hypothesis is that autoimmunity-associated genes participate in the control of vitiligo susceptibility. To investigate this hypothesis, we tested for association between vitiligo and genes CYP27B1, REL, TNFAIP3 and IL2/IL21, all previously related to autoimmune diseases associated with vitiligo. The study was performed using two independent population samples: a family-based discovery set (211 trios) and a replication set (131 cases/119 controls). Statistically significant association with vitiligo was detected between markers of the REL and IL2 gene in the family-based sample. Both association signals were concentrated among patients displaying autoimmune comorbidity and non-segmental vitiligo. Evidence for validation was detected for IL2 marker. Our findings suggest REL and IL2 as new vitiligo susceptibility genes and reinforce the hypothesis of a shared genetic mechanism controlling vitiligo and other autoimmune diseases.     

Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease Activity

Background:Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis.Results:Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease.Conclusions:HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease.