Altered circulating memory T cells in vitiligo cases followed NB-UVB therapy.

BACKGROUND: Vitiligo represents a commonly diagnosed autoimmune disease caused by the depletion of epidermal melanocytes. Many subsets of T cells contribute to vitiligo pathogenesis, including resident and circulating memory T cells. OBJECTIVES: To analyze the amounts of CD4+ and CD8+ memory T-cell subsets in peripheral blood specimens from vitiligo patients and alterations caused by narrowband ultraviolet B (NB-UVB) phototherapy. METHODS: Circulating CD4+ and CD8+ central memory T (TCM ) and effector memory T (TEM ) cell frequencies in 33 patients with non-segmental vitiligo and 16 healthy donors were evaluated by flow cytometry. Related chemokine levels were also detected. RESULTS: Peripheral blood CD4+ TCM and CD8+ TCM counts were markedly reduced in vitiligo cases while they were higher in active vitiligo compared with stable vitiligo cases. Circulating CD8+ TCM frequency in vitiligo was closely related to disease duration. Interestingly, CD4+ TCM and CD8+ TCM frequencies, alongside CXCL9 and CXCL10 amounts in peripheral blood of patients with vitiligo, were significantly decreased after NB-UVB phototherapy. CONCLUSIONS: Decreased frequencies of circulating CD4+ TCM and CD8+ TCM by NB-UVB suggest a possible immunosuppressive effect of phototherapy. The chemokines CXCL9 and CXCL10 are the bridge between circulating and skin resident memory T cells. NB-UVB blocks the homing of circulating memory T cells into vitiligo lesions by down-regulating CXCL9 and CXCL10. Targeting the above proteins could provide novel, durable treatment options to cure and prevent flares of this disease.

Immunohistochemical study of toll-like receptors 2, 4, and 9 expressions in pemphigus and bullous pemphigoid lesions.

Pemphigus and bullous pemphigoid (BP) are severe autoimmune skin diseases. Whether innate immunity could be a trigger or a part of the pathogeneses is unknown. Toll-like receptors (TLRs) are important components of the innate immune system, with no previous evaluation of TLRs in autoimmune bullous diseases. This work aims to investigate TLRs 2, 4, and 9 expressions in pemphigus and bullous pemphigoid. Thirty-six patients with pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), and six healthy controls were studied. Skin biopsies from the patients and the controls were examined immunohistochemically for TLR2, 4, and 9 expressions. The TLR4 expressed mainly at the basal layer of epidermis in controls, but in the cases with autoimmune bullous diseases, TLR4 staining located at basal layer and suprabasal layer, even superficial layer of epidermis. The immunostaining-intensity-distribution (IID) index of TLR4 in patients with PF (13.83, P = 0.001), PV (13.08, P = 0.003), and BP (11.42, P = 0.042) were significantly higher than that of the controls (6.17). TLR2 and TLR9 showed no significantly changes at epidermal expression (P > 0.05) compared with controls. There was no correlation found between the expressions of these TLRs. This work, thus, shows a re-localization of TLR4 expression sites with increased expression in pemphigus and bullous pemphigoid lesions. Targeting TLR4 signaling is expected to be a novel treatment strategy for autoimmune bullous diseases.

Spontaneous regression of generalized eruptive histiocytosis: possible involvement of apoptosis?

Generalized eruptive histiocytosis (GEH) is a rare generalized non-X histiocytosis, first described in 1963 by Winklemann and Muller. Since then more than 20 patients with GEH, mainly adults but also a few children, have been reported. We report a case of GEH in a middle-aged woman with spontaneous regression, in which the ultrastructural findings of apoptosis were observed.

Genetic epidemiology of vitiligo: a study of 815 probands and their families from south China.

BACKGROUND: Genetic factors are thought to be involved in the development of vitiligo. AIM: To explore the possible genetic model of vitiligo by analyzing the genetic characteristics of 815 patients and their families from south China (Zhejiang Province). METHODS: Data for 815 patients with vitiligo were obtained by questionnaire. The inheritance pattern estimation, heritability calculation, and complex segregation analysis were performed using the Penrose method, Falconer regression method, and SAGE-REGTL program, respectively. RESULTS: In 815 vitiligo probands, 128 (15.7%) had a family history. The ratio of the sibling prevalence rate to the population prevalence rate (s/q) approached 1/square root q using the Penrose calculation, and the heritability degrees of vitiligo in the first- and second-degree relatives were 59.6% and 55.2%, respectively. The complex segregation analysis suggested that the dominant model was the best-fit genetic model for vitiligo. CONCLUSIONS: Genetic factors play an important role in the occurrence of vitiligo, and the genetic model of vitiligo in this population is consistent with a polygenetic or multifactorial inheritance in a dominant major gene pattern.

Epidemiological investigation of human papillomavirus infection in men attending a sexually transmitted disease clinic in Hangzhou area.

OBJECTIVE: To investigate the epidemiological characteristics of human papillomavirus (HPV) infection in men attending a sexually transmitted diseases (STD) clinic in Hangzhou area. METHODS: Male subjects (n=375) aged 18-70 years, attending the STD clinic were recruited. Urethral swabs were assessed for HPV DNA using polymerase chain reaction (PCR) with the consensus primers MY09/11. HPV genotypes of positive PCR products were determined by restriction fragment length polymorphisms and direct sequence analysis. RESULTS: Of the 375 swabs collected, 305 (81.3%) yielded sufficient DNA for the subsequent HPV analysis. Among the 305 subjects, the prevalence of HPV was 13.8%. Nononcogenic HPV types were found in 8.5% (26/305) of subjects, oncogenic types in 4.3% (13/305), and multiple types in 1.0% (3/305). The prevalence of HPV infection was higher in subjects from urban area than in those from rural area (P < 0.05). The prevalence was also higher in those who received fewer years of education (P < 0.05) and those who had more sex partners (P < 0.05). CONCLUSIONS: HPV infection among men at high risk is not uncommon. The detection rate of HPV DNA is significantly related to some sociodemographic factors, such as residence, educational level and the number of sex partners.

[Study on genetic epidemiology on 815 patients with vitiligo in Zhejiang area].

OBJECTIVE: Genetic factors are thought to be involved in the development of vitiligo. The aim of this study is to explore the possible genetic model of vitiligo by analyzing the genetic characteristics of 815 patients from Zhejiang province. METHODS: Data for 815 patients with vitiligo together with their first- and second-degree relatives were obtained using a standardized questionnaire. All these information was requested to confirm the answers about family history in order to reduce the possibility of 'recall' bias. The 815 probands would include 411 (50.43%) males and 404 (49.57%) females with a varied age from 2 months to 71 years old. Since the information on general prevalence of vitiligo in this area was absent, a control group was set up to facilitate the calculations of heritability degree. 468 persons of the control group were from non-vitiligo population with a sex ratio of 241(male): 227(female) with varied age of 4 months to 80 years old. Both gender and age were comparable between the vitiligo and the control population. The inheritance pattern estimation, heritability calculation and complex segregation analysis were performed with Penrose method, Falconer regression method and SAGE-REGTL program. RESULTS: In 815 vitiligo probands, 128 had and 687 had not family histories, with a heritability rate of 15.7%. The vitiligo prevalence in proband's first degree relatives was 2.580%, higher than the prevalence of 0.618% in second degree relatives, and both of them were higher than general prevalence: 0.192%. By Penrose method, the rates on different catagories were as follows: sibling prevalence rates s = 0.080 18; population prevalence rate q = 0.001 92; s/q = 41.76. The ratio of s/q did not approach 1/2q (260.42) or 1/4q (130.21), but approached 1/square root of q(22.82), suggesting vitiligo was consistent with a mode of polygenic inheritance. Using Falconer's method, heritabilities of vitiligo in first-and second degree relatives of probands were 59.61% (95% confidence interval 65.37-53.84) and 55.20% (95% confidence interval 43.88-66.52), respectively. The weighted average of heritability in all relatives was 58.7% (95% confidence interval 53.56-63.83). The results of complex segregation analysis suggested that major gene model including the Mendelian dominant, recessive and additive hypotheses were not rejected (P > 0.05). Purely environmental model and no transmission model were rejected at a 0. 001 significance level. According to AIC, Mendelian dominant inheritance was the best-fitted hypothesis. CONCLUSION: Genetic factors played an important role in the occurrence of vitiligo, and the genetic model of vitiligo could serve as the polygenetic or multifactorial inheritance with major gene trait.

[Study on gene mutation in 11 Chinese families with Hailey-Hailey disease].

OBJECTIVE: To screen and identify gene mutations of 11 Chinese patients with Hailey-Hailey disease (HHD). METHODS: Cases of HHD were diagnosed by history, clinical menifestations and pathology. Then genomic DNA samples of patients were extracted from perpheral blood leukocytes, and polymerase chain reaction(PCR), DNA sequencing were performed. RESULTS: We found five mutations in ATP2C1 gene including 3 nonsense mutations and 2 splicing mutations. Four of them were novel mutations. CONCLUSION: Both nonsense mutation and splicing mutation could affect the rusult of transcription, translation, and the functions of protein encoded by ATP2C1 gene, so the mutations reported in this study is the underlying cause of HHD.

Keratin 1 and keratin 10 mutations causing epidermolytic hyperkeratosis in Chinese patients.

Epidermolytic hyperkeratosis (EHK) is a rare dominantly inherited skin disorder with erythroderma and hyperkeratosis. Mutations have been found in keratin 1 (K1) or keratin 10 (K10) gene. In the present study, we reported three sporadic and one familial Chinese EHK patients with their mutation findings. All the mutations turned out to be single heterozygous point substitutions. A novel mutation designated as E477K of K1 was identified in one patient, and previous reported mutations in codon 156 of K10, i.e. R156S, R156P, R156H were found in other patients. This is the first report of the keratin mutations in Chinese kindreds. The results showed that the possible correlation between the genotype and phenotype in these patients was complex, not only depended on the position of the mutation but also on the actual amino acid substitution. And palmoplantar keratoderma (PPKD) can be an accompanied symptom caused by either K1 or K10 mutation.