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1.
BackgroundVitiligo is a common acquired pigmentary disease caused by destruction of epidermal melanocytes in underlying autoimmune response. Few studies have been focused on the role of chemokines in non-segmental vitiligo (NSV) concomitant with autoimmune thyroid disease (AITD) and alopecia areata (AA).ObjectiveThe aim of this study was to determine the best serum biomarker for predictive role in the progression of vitiligo and to evaluate the influence of AA and/or AITD on vitiligo by using the biomarker.MethodsThis prospective cohort study recruited 45 NSV patients: 14 without either AITD or AA, 12 with AITD, 11 with AA, and 8 with both AITD and AA. Serum levels of CXCL1, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13, and CXCL16 were analyzed by ELISA. CXCR3 mRNA expression was detected on PBMCs by RT-PCR. Improvement was evaluated using repigmentation scales.ResultsSerum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with AITD or AA alone than in those without AITD or AA. Moreover, serum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with both AITD and AA than in those with AITD or AA alone. Poorer repigmentation was observed in NSV patients with both AA and AITD than in those with AA or AITD alone.ConclusionCXCL10 could be a biomarker to predict the progression of NSV. Dermatologists should pay much attention to those NSV patients concomitant with AITD and/or AA, for comorbidity might lead to more active autoimmune reaction.  相似文献   

2.
Background Vitiligo/nonsegmental vitiligo (NSV) is often associated with thyroid dysimmunity although very few reports have studied this association using multivariate logistic regression. Objective To identify weighted factors associated with the presence of autoimmune thyroid disease (AITD) in a large cohort of patients with vitiligo/NSV. Methods This was a prospective observational study in 626 patients with a confirmed diagnosis of vitiligo/NSV attending the vitiligo clinic of the University Hospital Department of Dermatology, Bordeaux, France, from 1 January 2006 to 1 May 2012. The Vitiligo European Task Force (VETF) questionnaire was completed for each consecutive patient. AITD was defined as the presence of significant levels of serum antithyroperoxidase antibodies or evidence of autoimmune thyroiditis. Univariate and multivariate logistic regression procedures were conducted to identify factors associated with AITD in this cohort of patients with vitiligo/NSV. Results A total of 626 patients with vitiligo/NSV were included, of whom 131 had AITD (AITD‐vitiligo). Stress as an onset factor, familial history of AITD, body surface involvement and duration of the disease were positively associated with AITD‐vitiligo using univariate analysis, whereas female sex, age at onset of vitiligo, personal history of autoimmune disease and localization on the trunk were found to be independently associated with AITD‐vitiligo. Conclusion Vitiligo associated with AITD has clinical features distinct from vitiligo without AITD. In particular, female patients, and patients with longer duration of disease and greater body surface involvement are more likely to present with AITD and should thus be monitored for thyroid function and antithyroid antibodies on a regular basis.  相似文献   

3.
目的 探讨中国汉族人群8-羟鸟嘌呤DNA转葡糖基酶1(OGG1)基因功能性单核苷酸多态性(SNP) rs1052133(C/G)位点与白癜风的相关性。方法 白癜风患者800例和健康对照组800例,采用PCR及限制性片段长度多态性方法(PCR-RFLP)检测OGG1基因rs1052133位点多态性分布,χ2检验和非条件Logistic回归分析评估该位点多态性与白癜风罹患危险的相关性。白癜风患者83例和健康对照组83例,采用8-羟基脱氧鸟苷(8-OHdG) ELISA检测试剂盒检测外周血血清中8-OHdG的水平,采用t检验分析两组之间的差异。结果 白癜风组rs1052133位点CC、CG和GG基因型频率分别为16.8%、54.0%、29.2%,健康对照组为21.4%、52.8%、25.8%,两组间差异有统计学意义(χ2 = 6.26,P < 0.05)。白癜风组rs1052133位点G等位基因携带者显著高于健康对照组(56.2%比52.2%,χ2 = 5.16,P < 0.05)。携带有rs1052133位点CG或GG基因型的个体罹患白癜风的危险性显著增加[CG基因型χ2 = 3.98,P < 0.05,校正OR值 = 1.31 (1.01 ~ 1.70);CG基因型χ2 = 6.01,P < 0.05,校正OR值 = 1.45 (1.08 ~ 1.94)],尤其是女性患者、非节段型、病情活动、病程较长、有家族史、无伴发自身免疫性疾病的患者。携带有rs1052133位点CG或GG基因型的白癜风患者外周血血清中8-OHdG的水平显著高于携带CC基因型的患者,8-OHdG水平分别为(838.23 ± 294.11) ?滋g/L和(593.84 ± 190.14) ?滋g/L,两组比较,t = 3.63,P < 0.01。结论 OGG1基因功能性SNP rs1052133位点的多态性与白癜风的发病紧密相关,可能由其修复能力降低所致。 【关键词】 白癜风; 多态性,单核苷酸; OGG1基因; 8-羟基脱氧鸟苷  相似文献   

4.
Vitiligo is a pigmentary skin disorder characterized by the chronic and progressive loss of melanocytes. Although the etiology of vitiligo is still unknown, several theories have been proposed to explain the pathogenesis of vitiligo including autoimmune, neural, self-destruction, oxidative stress, and genetic theories. Human leukocyte antigen (HLA)-G is a nonclassic, major histocompatibility complex class I molecule that plays an important role in suppression of the immune response. Several recent studies have provided evidence that a 14 bp insertion (INS)/deletion (DEL) polymorphism in the HLA-G gene might be associated with autoimmune disease. Our aim in this study was to determine whether the 14 bp INS/DEL polymorphism in the HLA-G gene contributes to the risk of developing non-segmental vitiligo (NSV) in the Korean population. We conducted a case–control association study of 192 NSV patients and 491 matched, unaffected controls. The HLA-G 14bp INS/DEL polymorphism was analyzed by gene scan after amplification using the polymerase chain reaction. Genotype frequencies for the 14bpINS/DEL were different between the vitiligo group and Korean control group. The proportion of subjects with a homozygote 14bpINS/14bpINS genotype was significantly higher in the vitiligo group compared with the control group (7.1 vs. 3.5 %, OR 2.25, 95 % CI 1.06–4.76, p = 0.039 in the recessive model). Our results suggest that the HLA-G 14bpINS/DEL polymorphism is associated with the development of NSV in the Korean population.  相似文献   

5.
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.  相似文献   

6.
7.

Background

Vitiligo is an autoimmune polygenic disorder characterized by loss of pigmentation due to melanocyte destruction. The PTPN22 gene +1858 C>T single nucleotide polymorphism (rs2476601) has been shown to be associated with various autoimmune disorders.

Objective

The aim of this study was to investigate whether the PTPN22 gene +1858 C>T single nucleotide polymorphism is associated with susceptibility to generalized vitiligo in a Turkish population.

Methods

One hundred and seven patients with generalized vitiligo, and one hundred and twelve gender-, age-, and ethnic-matched controls were enrolled in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism.

Results

The PTPN22 +1858 C>T genotype and allele frequencies of the generalized vitiligo patients did not differ significantly from those of healthy controls.

Conclusion

We found no association between the PTPN22 +1858 C>T gene polymorphism and vitiligo susceptibility in Turkish generalized-vitiligo patients.  相似文献   

8.
Vitiligo is an autoimmune disease of the skin that results in localized or disseminated white macules. One common feature of several existing classification protocols is the distribution of the disease into two main subtypes, non-segmental vitiligo (NSV) and segmental vitiligo (SV). SV is characterized by depigmentation spreading within one or more skin segments while NSV is widespread. Several clinical-epidemiological observations suggest that SV has distinct autoimmune pathophysiology compared to NSV. Furthermore, the clinical distribution pattern of SV lesions closely resembles other melanocyte mosaicism diseases. These observations led us to hypothesize that SV is caused by a localized autoimmune reaction targeting epidermal mosaicism melanocytes. Here, we proposed examples of experimental approaches to assess mosaicism in SV patients.  相似文献   

9.
10.
Vitiligo is an acquired hypomelanotic skin disorder characterised by circumscribed depigmented macules resulting from the loss of functional melanocytes from the cutaneous epidermis and autoimmunity has been suggested to play a role in the pathogenesis of the disease. Recently, an insertion/deletion (I/D) polymorphism of a 287-base pair repetitive sequence in intron 16 of the angiotensin converting enzyme (ACE) gene has been associated with autoimmune disease and with the development of vitiligo. In this study, the distribution of ACE gene I/D genotypes was investigated in a population of 106 English patients with generalised (non-segmental) vitiligo and 174 ethnically matched healthy controls using a restriction fragment length polymorphism-polymerase chain reaction genotyping method. No significant difference in the frequencies of II, ID and DD genotypes was detected between vitiligo patients and control subjects (P=0.35). The same result was evident for the genotype distribution in vitiligo patients with an autoimmune disease and for those without when compared with controls (P=0.33 and P=0.53, respectively). In addition, the results indicated that the D allele was not significantly over-represented in the group of patients with vitiligo compared with controls (P=0.42) and that this was also the case for patients with and without associated autoimmunity (P=0.40 and P=0.62, respectively).  相似文献   

11.
Background Vitiligo has been found to be associated with different HLA antigens in different ethnic groups. In our previous genome‐wide association study (GWAS), we identified independent association signal of rs9468925 (P = 2.21 × 10?33, OR = 0.74) within HLA‐C‐HLA‐B region. Objectives To explore the association between rs9468925 polymorphism within MHC and the clinical features of generalized vitiligo. Methods The study, using 5566 cases and 6462 controls from previous GWA study investigated the single and combined (GA + GG) genotypic distribution of rs9468925 in subsets of vitiligo patients having different clinical features. We performed a QTL analysis (quantitative trait locus) for age of onset with genotype of rs9468925. Results The GA + GG genotypic distribution of SNP rs9468925 tested with an additive model was found to be significantly different in subgroups of patients of >20 vs. <20 years old (genotypic P = 2.57 × 10?4, combined P = 3.0 × 10?3, OR = 0.77, 95% CI: 0.64–0.92), and in patients with different clinical subtypes of vitiligo (genotypic P = 0.03, combined P = 5.0 × 10?3). However, there was no statistical significance for familial history, halo nevi involvement and autoimmune disease involvement. Conclusions Allele G of rs9468925 on HLA‐C‐HLA‐B may be associated with a higher risk of vitiligo. Our study showed a significant genotypic variation between patients with age of onset ≤20 years and age of onset >20 years. Obvious clinical differences of generalized vitiligo related to genotypic variation found in the Chinese Han population were confirmed in this study.  相似文献   

12.
Background Vitiligo is a pigmentary skin disorder characterized by a chronic and progressive loss of melanocytes. Although the aetiology of vitiligo is currently unknown, several theories have been proposed to explain the pathogenesis of this disease, including autoimmune, neural, self‐destruction, oxidative stress, and genetic theories. Thioredoxin domain containing 5 (TXNDC5) is a newly identified member of the thioredoxin family. TXNDC5 has a protein disulphide isomerase‐like domain which plays an important role in protein folding and chaperone activity, against endoplasmic reticulum (ER) stress induced by oxidative stress within the ER. Objectives To determine whether variation in the TXNDC5 gene contributes to the risk of developing nonsegmental vitiligo (NSV) in the Korean population. Methods We conducted a case–control association study of 230 patients with NSV and 417 matched, unaffected controls. Seven single nucleotide polymorphisms (SNPs) in the TXNDC5 gene were selected for study. Results Of the selected SNPs, three exonic SNPs (rs1043784, rs7764128 and rs8643) were statistically associated with NSV. Among them, rs1043784 remained a statistically significant association following Bonferroni correction. These three SNPs were located within a block of linkage disequilibrium; the haplotypes AGG and GAA, consisting of rs1043784, rs7764128 and rs8643, demonstrated a significant association with NSV. Conclusions These results suggest that TXNDC5 gene polymorphisms are associated with the development of NSV in the Korean population.  相似文献   

13.
目的探讨白癜风与细胞毒性T淋巴细胞相关抗原4(CTLA4)基因外显子1第49位点A/G多态性的相关性。方法采用多聚酶链反应限制性片段长度多态性(PCRRFLP)技术分析59例白癜风患者和124例健康对照者CTLA4基因外显子1第49位点的基因型。结果白癜风患者CTLA4基因外显子1第49位点的各基因型分布和等位基因频率与健康对照者相比,无显著性差异(χ2=0.735,P>0.05;χ2=0.684,P>0.05);当患者按有无自身免疫性疾病分类后,伴及不伴有自身免疫性疾病的白癜风患者CTLA4基因外显子1第49位点的各基因型分布及等位基因频率与健康对照者相比较无统计学意义(χ2=2.614,P>0.05;χ2=2.317,P>0.05);当患者按临床型别分类后,各型别等位基因频率与健康对照者相比无统计学意义(χ2=3.076,P>0.05)。结论CTLA4基因外显子1第49位碱基A/G多态性与白癜风的发病可能无相关性;将白癜风患者按有无自身免疫性疾病分类后,发现甚至与白癜风同时伴发的自身免疫性疾病也与CTLA4外显子1第49位点A/G49多态性无关。  相似文献   

14.
BackgroundVitiligo is an acquired and progressive mucocutaneous disease resulting from the loss of active epidermal melanocytes. Metabolic syndrome (MetS) affects about 25% of the world’s population and is linked to inflammatory skin diseases including vitiligo. Fatty Acid-Binding Protein 4 (FABP4) is an intracellular lipid chaperone. FABP4 is closely associated with MetS.ObjectivesTo evaluate the serum level of FABP4 in vitiligo patients and its relation to MetS in the investigated cases.MethodsThis case control study was conducted on 45 patients having non segmental vitiligo and 45 matched controls. Their lipid profile, blood glucose and serum FABP4 levels were measured.ResultsThere were significant elevations in FABP4 (p < 0.001), cholesterol (p < 0.001), triglycerides (p = 0.005), and glucose (fasting [p = 0.001] and 2 hours post prandial [p < 0.001]) levels in patients in comparison with controls. MetS was significantly more prevalent among vitiligo patients (p < 0.001) and associated with high FABP4 serum levels (p = 0.037). In vitiligo patients, there were significant positive correlations between FABP4 serum levels and triglycerides (p = 0.047), cholesterol (p = 0.001) and LDL (p = 0.001) levels and negative correlation regarding HDL level (p = 0.009). FABP4 level was a significantly good diagnostic test for early detection of vitiligo (p < 0.001).Study limitationsThe small number of studied subjects.ConclusionsFABP4 may play an active role in the disease process of vitiligo that could be mediated through associated dyslipidemia and hyperglycemia. FABP4 may be a marker of vitiligo helping in its early diagnosis, but it does not appear to be useful for determining vitiligo severity, activity or associated MetS.  相似文献   

15.
Background Although mixed forms have been described recently, segmental (SV) and nonsegmental vitiligo (NSV) are considered as clinically distinct. However, limited epidemiological data are available to help distinguish associated factors, and recent genome‐wide association studies have been restricted to NSV. The higher prevalence of SV in children is helpful when comparing the two major presentations of the disease. Objective To compare factors associated with SV and NSV, especially for markers of autoimmunity or autoinflammation. Methods We conducted a single‐centre prospective observational study in patients aged 17 years or under with a confirmed diagnosis of SV or NSV at the vitiligo clinic between 1 January 2006 and 1 July 2010. The Vitiligo European Task Force questionnaire was completed for each patient, and thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Other forms of vitiligo (focal, mucosal, not classifiable) were excluded. Results A total of 213 children were included, 142 with NSV, 59 with SV and 12 with mixed vitiligo. There was no significant statistical difference for sex or age at onset between patients with SV and NSV. Halo naevi were significantly more frequent in NSV than in SV [odds ratio (OR) 7·58, P < 0·01). Patients with NSV more frequently had a positive family history of vitiligo (OR 2·25, P = 0·02) and a marked familial autoimmunity background (OR 2·22, P = 0·01). Conclusions Our study clearly shows that features of inflammation (pruritus)/autoimmunity (halo naevi, thyroid antibodies) are strongly linked to NSV, together with a familial background of vitiligo and autoimmunity.  相似文献   

16.
BackgroundVitiligo is a chronic, common disease of unknown etiology, and oxidative stress is suggested to have a role in its etiopathogenesis.ObjectiveAdvanced oxidation protein products (AOPPs), prooxidant-antioxidant balance (PAB), and ferric-reducing antioxidant power (FRAP) were evaluated regarding their role in the pathogenesis of vitiligo as well as their relationship with clinical presentation and disease severity, and these parameters were compared with those of healthy controls.MethodsThe study included 53 patients with vitiligo and 20 healthy volunteers as the control group. AOPP level, PAB, and FRAP were determined by colorimetric methods.ResultsPAB and FRAP level were significantly higher in patients with vitiligo than in healthy controls (p<0.001). The AOPP levels in vitiligo patients were not statistically significantly higher than those in healthy controls. The Vitiligo Area Scoring Index positively correlated with disease duration (rs: 0.531, p<0.001).ConclusionTo the best of our knowledge, this is the first report of AOPP and PAB status in vitiligo. PAB may be used as an indicator for oxidative stress in the etiopathogenesis of vitiligo. Our results show that these parameters may play a major role in the melanocyte damage observed in vitiligo. Further studies are required to confirm the mechanisms underlying this effect.  相似文献   

17.
The aim of this study was to determine whether or not promoter polymorphisms of the class I major histocompatibility complex (HLA-E, HLA-F, and HLA-G) are associated with susceptibility to vitiligo. To identify a possible association with vitiligo, 241 patients with non-segmental vitiligo (NSV) and 395 healthy controls were recruited in this study. Three promoter single nucleotide polymorphisms (SNPs; rs1264459 of HLA-E, rs9258170 of HLA-F, and rs1736936 of HLA-G) were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and direct sequencing. Multiple logistic regression models (co-dominant 1, co-dominant 2, dominant, recessive, and log-additive models) were applied for odds ratios (ORs), 95% confidence intervals (CIs), and P values. To obtain the defined results, P values were recalculated by a Bonferroni correction. After the Bonferroni correction, the genotype of the SNP (rs1736936) of HLA-G was shown to have significant association with NSV (P = 0.045 in the recessive model). The genotype frequencies of the HLA-G SNP (rs1736936) had a significant correlation with the age of onset of NSV (P = 0.016 in the co-dominant 1 model and P = 0.027 in the dominant model). Our results suggest that HLA-G, but not HLA-E and HLA-F, may be associated with susceptibility to NSV in the Korean population.  相似文献   

18.
Vitiligo is a common depigmentary skin disease that may follow a pattern of multifactorial inheritance. The essential factors of its immunopathogenesis is thought to be the selective destruction of melanocytes. As a new class of microregulators of gene expression, miRNA have been reported to play vital roles in autoimmune diseases, metabolic diseases and cancer. This study sought to characterize the different miRNA expression pattern in the peripheral blood mononuclear cells (PBMC) of patients with non‐segmental vitiligo (NSV) and healthy individuals and to examine their direct responses to thymosin α1 (Tα1) treatment. The miRNA expression profile in the PBMC of patients with NSV was analyzed using Exiqon's miRCURY LNA microRNA Array. The differentially expressed miRNA were validated by real‐time quantitative polymerase chain reaction. We found that the expression levels of miR‐224‐3p and miR‐4712‐3p were upregulated, and miR‐3940‐5p was downregulated in the PBMC. The common clinical immune modulator Tα1 changed the miRNA expression profile. Our analysis showed that differentially expressed miRNA were associated with the mechanism of immune imbalance of vitiligo and that Tα1 could play an important role in changing the expression of these miRNA in the PBMC of patients with NSV. This study provided further evidence that miRNA may serve as novel drug targets for vitiligo therapeutic evaluation.  相似文献   

19.
BACKGROUND: Vitiligo is a skin disorder affected by genetic, environmental, local and endocrine factors. Endothelin-1, which is expressed by keratinocytes, has paracrine effects on melanocytes, influencing their homeostasis, proliferation and pigmentation. It is thought to play a role in the skin response to 311-nm, narrow-band ultraviolet irradiation. OBJECTIVE: To investigate the association of endothelin-1 gene (EDN1) polymorphisms with vitiligo in a Korean population. METHODS: To evaluate the expression of endothelin-1 in cultured human keratinocytes after irradiation with narrow-band ultraviolet B (NBUVB), we performed RT-PCR and ELISA. In addition, we genotyped 312 vitiligo patients and 313 matched-healthy controls, and compared the genotype, allele and haplotype frequencies of EDN1 polymorphisms (intron 4 G/A, rs2071942 and exon 5 G/T, rs5370) between the two groups, using PCR-restriction fragment length polymorphism. The effects of sex, onset age, the presence of autoimmune diseases, family history and clinical type were analysed statistically. RESULTS: NBUVB induced the expression of endothelin-1 in cultured human keratinocytes. The genotype distributions and allele frequencies of EDN1 polymorphisms did not differ significantly between vitiligo patients and healthy controls. Moreover, the results were not related to sex, onset age, the presence of autoimmune diseases or family history. Interestingly, the haplotype frequencies of EDN1 polymorphisms differed significantly between vitiligo patients and healthy controls. When analysed according to clinical type, the haplotype frequencies in the focal and segmental clinical types differed significantly from healthy controls. CONCLUSION: This study suggests that EDN1 is related to the development of vitiligo in the Korean population.  相似文献   

20.
BackgroundVitiligo is a common skin disorder in which melanocytes are destroyed by auto-reactive immune responses. The loss of melanocytes results in the appearance of depigmented areas in different parts of the body. Cytokines have remarkable roles in the pathogenesis of vitiligo, such as IL-1, IL-6, and TNF-α; interleukin 27 (IL-27) is a new member of the IL-6/IL-12 family, mainly released by activated antigen-presenting cells. IL-27 has been suggested to function as a pro-inflammatory as well as an anti-inflammatory cytokine. Altered concentrations of IL-27 have been shown in various auto-immune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis. No studies have been conducted to determine the expression of this cytokine in vitiligo patients.ObjectiveThe objective of this study was to determine the serum concentration of IL-27 in vitiligo patients and compare it with normal individuals.MethodsThe serum concentration of IL-27 in 79 vitiligo patients was evaluated in comparison to 45 healthy controls using ELISA assay.ResultsResults showed decreased concentration of IL-27 in vitiligo patients as compared with healthy subjects (p = 0.026). Furthermore, no correlation between IL-27 concentrations and disease parameters such as vitiligo severity and the extension of the depigmented area was observed.Study limitationA larger sample size would be more recommended for this study.ConclusionThe reduction in the serum levels of IL-27 in vitiligo patients compared to normal subjects suggested the possible anti-inflammatory role of this cytokine in vitiligo. Thus, IL-27 may be considered as a new target for the manipulation of the immune system in vitiligo patients.  相似文献   

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