Identification of pigment cell antigens defined by vitiligo antibodies.

Patients with vitiligo have circulating antibodies to pigment cells. To characterize this response further and to identify the antigens defined by vitiligo antibodies, sera of 23 patients with vitiligo and 22 patients with unrelated conditions were analyzed by immunoprecipitation and SDS-PAGE analysis of 125I-labeled cell antigens on pigment and control cells. Antibodies to pigment cell antigens were present in 18 (78%) of the patients with vitiligo but in only three (14%) of the control patients (p less than 0.05). The antibodies were directed to one or more antigens with molecular weight (MW) in kilodaltons (kD) of approximately 35, 40-45, 75, 90, or 150. The responses were most commonly directed to the 40-45-kD, 75-kD, and 90-kD antigens. Antibodies to these antigens were present in 74%, 57%, and 35% of vitiligo patients versus in 14%, 9%, and 0% of control individuals. The 35-kD and 90-kD antigens were preferentially expressed on human pigment cells, whereas the 40-45-, 75-, and 150-kD antigens were expressed on both pigment and control cells. These antigens were labeled by the lactoperoxidase technique, suggesting that they are cell surface antigens. These results confirm that antibodies to pigment cells are associated with vitiligo. These antibodies are directed to several cell surface antigens, some of which are preferentially expressed on pigment cells.     

Circadian rhythm of natural killer cell activity in vitiligo

Ten patients with vitiligo, either in the active (six cases) or static (four cases) phase, and twelve healthy control subjects were studied with a standard cytotoxicity assay to evaluate the circadian rhythm of natural killer cell activity from peripheral blood mononuclear cells. The natural killer cell activity was measured at the zero, sixth, twelfth, and eighteenth hours of the day. The results demonstrated that patients with vitiligo had significantly higher natural killer cell activity compared with normal controls. When patients with static and active vitiligo were compared, those with the static form had increased natural killer cell activity at all times except noon, whereas those with active form had increased natural killer cell activity only at 0600 and 1800. These changes shifted the acrophase of the circadian rhythm of each group. Indeed, by cosinor analysis, both patients with vitiligo and normal controls had similar circadian rhythms, but the acrophase was shifted from 0602 in control subjects to 0435 in the ten patients with vitiligo. The acrophase in the six patients with active vitiligo was found to be closest to that of normal controls (0508). These findings indicate that natural killer cell activity abnormalities are more marked in the static rather than in the active form of vitiligo.     

Serum anti-tumour antibodies and auto-antibodies in vitiligo

Anti-tumour antibody was sought in the sera of three groups of patients; idiopathic vitiligo, malignant melanoma and miscellaneous skin disorders. No precipitating antibody to a series of prepared pigmented tumour antigens was demonstrated. All sera were tested for a number of auto-antibodies. No significant differences were detected between the groups. The evidence for an immunological factor in the causation of vitiligo remains circumstantial only.     

Behavior of pigment cells on lesions of the pigmented venus with vitiligo.

When vitiligo occurred on lesions of the pigmented nevus, the behavior of pigment cells in this nevus was investigated. Three cases of giant hairy nevi, seven cases of moles, three cases of Mongolian spots and eleven specimens in nine cases of halo nevi were used. Giant hairy nevi combining with vitiligo showed intensive decreases in nevus cells, particularly superficial A and B-type nevus cells. The epidermal dopa-positive melanocytes and melanin granules in the epidermis decreased, but still remained. On the other hand, moles in vitiligo showed an almost complete disappearance of epidermal dopa-positive melanocytes and melanin granules in the epidermis; nevus cells in the dermis decreased only slightly. Mongolian spots with vitiligo showed an epidermis similar to vitiligo, but the dermal melanocytes were hardly changed. Halo nevi exhibited an intensive decrease and degeneration of nevus cells and marked lymphocytic infiltration. Some of them showed disappearance of epidermal dopa-positive melanocytes and melanin granules in the epidermis. The characteristic findings of vitiliginous skin are mostly restricted to epidermis. In contrast, however, it is interesting to note that, on the lesions of nevocellular nevi with vitiligo, the dermis also exhibited some decrease and degeneration of nevus cells and lymphocytic infiltration.     

Melanocyte antigen‐specific antibodies cannot be used as markers for recent disease activity in patients with vitiligo

Background Objective parameters to assess disease activity in non‐segmental vitiligo are lacking. Melanocyte antigen‐specific antibodies are frequently found in the sera of patients with vitiligo and the presence of these antibodies may correlate with disease activity. Objective To investigate the relationship between melanocyte antigen‐specific antibodies and recent disease activity in patients with vitiligo and to evaluate the potential usefulness of this objective parameter in daily clinical practice. Methods The prevalence of tyrosinase, melanoma antigen recognized by T‐cells‐1 (MART1), melanin‐concentrating hormone receptor‐1 (MCHR1), gp100 and tyrosine hydroxylase (TH) antibodies was evaluated in 21 patients with non‐segmental vitiligo and in 20 healthy controls. Results In 21 patients, nine (42.8%) showed antibody responses against tyrosinase, MART1, MCHR1, gp100 or TH. No antibody responses were found in the 20 controls. No correlation was found between the presence of antibodies and recent disease activity or other clinical characteristics such as age, gender, extension and duration of vitiligo. Conclusions In this study, 42.8% of the vitiligo patients showed an antibody response to melanocyte antigen‐specific antigens. However, the presence of antibodies against melanocytes did not correlate with recent disease activity or other relevant disease parameters, and for the moment screening for these antibodies in individual patients does not appear to be clinically relevant.     

Recognition of melanoma cell antigens with antibodies present in sera from patients with vitiligo

BACKGROUND: Patients with vitiligo show specific losses of integumentary melanocytes, probably due to autoimmunity against melanocytes. We attempted to determine the presence of antibodies against pigment cell antigens in the sera of vitiligo patients. METHODS: Detergent-solubilized human melanoma cells were submitted to electrophoretic separation and immunoblotted against serum samples obtained from 19 patients with vitiligo and from 20 age- and sex-matched healthy individuals. RESULTS: Eighty-nine per cent of patients with vitiligo had antibodies to one or more pigment cell antigens. Similar antibodies were detected in 20% of healthy individuals. Antigens of 165, 90, and 68 kDa were recognized by the antibodies present in sera from 11%, 26%, and 37% of vitiligo patients, respectively, and in none of the normal sera. All patients with familial vitiligo also had antibodies to these three proteins. CONCLUSIONS: Proteins of 165, 90, and 68 kDa are specifically recognized by antibodies present in the sera of vitiligo patients and in all patients with genetic vitiligo. Whether or not these proteins might be implicated in the destruction of melanocytes by the immune system in vitiligo remains to be evaluated.     

血清中亚甲基四氢叶酸还原酶活性与白癜风临床特征相关性研究

目的:明确白癜风患者血清中亚甲基四氢叶酸还原酶(MTHFR)活性与白癜风临床特征间的关系。方法:选择性别年龄相匹配的白癜风患者及健康对照各90例,采用ELISA法检测血清中MTHFR活性。结果:白癜风患者血清中MTHFR活性为(332.77±92.85)U/L,显著低于对照组的(403.66±96.56)U/L,(P0.0001)。静止期、进展期及快速进展期患者血清中MTHFR活性呈逐级降低趋势。MTHFR活性在患者性别、家族史、病程等方面无显著差异。结论:白癜风患者血清中MTHFR活性降低可能与白癜风疾病发展相关。     

Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity

Background Punch grafting is a simple and frequently used technique for the treatment of stable vitiligo, resistant to medical therapy. However, studies reporting long‐term results are exceptional. Objectives To evaluate the long‐term results of 2‐mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo. Methods We studied a prospective cohort study involving 61 patients (25 male, 36 female) with vitiligo vulgaris and nine patients (all male) with segmental vitiligo who underwent 2‐mm punch grafting more than 3 years ago. The main outcome measure was the degree of repigmentation of a single transplanted lesion as measured with a digital image analysis system with a mean follow‐up of 5·2 years. Results In patients with vitiligo vulgaris, 17 lesions (28%) showed excellent, 14 lesions (23%) showed good, 14 lesions (23%) showed fair and 16 lesions (26%) showed poor repigmentation. In patients with segmental vitiligo, seven of nine lesions (78%) showed excellent repigmentation. A cobblestone‐like effect was observed in 19 of 70 patients (27%). Disease activity after punch grafting was reported in 94% of patients with poor repigmentation but in only 18% of patients with excellent repigmentation (χ² test, P < 0·0005). Patients who reported disease activity after transplantation had a lower mean repigmentation than those who did not report disease activity (77% vs. 39%, P < 0·05). Conclusions Two‐millimetre punch grafting in vitiligo is an effective surgical procedure with long‐lasting effect. To prevent a cobblestone‐like effect, we advise the use of smaller grafts (1–1·2 mm). Disease activity after grafting, localization and type of vitiligo, prior ultraviolet B treatment and a Koebnerized donor site influence the long‐term outcome of punch grafting and should be taken into account in the selection of patients eligible for this treatment.     

白癜风患者病程与抗酪氨酸酶抗体的相关分析

目的 应用酪氨酸酶表达肽TYR240-479作为抗原,检测654例白癜风患者血清抗酪氨酸酶IgG抗体水平,分析白癜风患者病程与体内抗酪氨酸酶抗体水平的关联性。方法 以TYR240-479作为包被抗原,应用ELISA法检测白癜风患者血清中抗酪氨酸酶IgG抗体的滴度。不同病程患者抗体阳性检出率的差异以及病程与抗体水平的关联性分析应用卡方检验,多组率的两两比较应用Bonferroni校正。平均滴度差异比较应用one-way ANOVA,组间两两比较应用LSD－t检验。结果 各病程组抗体检测总阳性率具有显著性差异,P＝0.027,r＝0.112。其中病程1～5年（含5年）组与5～10年（含10年）组具有显著性差异,P＝0.007。病程是否超过5年与抗体水平的关联强度分析表明病程与抗体水平有关联,P＝0.025,OR＝1.473,95％CI（1.049-2.068）,但各病程组间抗体平均滴度无显著性差异。 结论 与病程超过5年的患者相比,病程5年之内的患者抗体阳性率更高,与抗体水平的关联更为紧密。白癜风病程与患者抗酪氨酸酶抗体水平有一定的关联性。     

血清中抗酪氨酸酶抗体的检测与白癜风活动性的关系

目的：探讨白癜风患者血清中抗酪氦酸酶IgG、IgM抗体滴度与疾病活动程度的关系和意义。方法：抗酪氯酸酶IgG、IgM抗体检测采用酶联免疫吸附试验（ELISA）方法。结果：①白癜风患者血清抗酪氨酸酶IgG抗体、平均滴度为0．316，显著高于正常对照组0．082（P〈0．001）；抗酪氨酸酶IgM抗体平均滴度为0．238，显著高于正常对照组0．065（P〈0．001），②活动期白癜风患者血清抗酪氨酸酶IgG、IgM抗体滴度明显高于稳定期白癫风患者（均P〈0.001）；泛发型白癜风患者血清抗酪氨酸酶IgG、IgM抗体滴度明显高于局限型白癜风患者（均P〈0．001）。③抗酪氨酸酶IgG、IgM抗体滴度与抗黑素细胞IGg抗体性呈正相关（均P〈0．001）；抗酪氨酸酶IgG、IgM抗体滴度与抗黑素细胞IgM抗体阳性呈正相关（均P〈0．001）。①糖皮质激素治疗后患者抗酪氨酸酶IgG、IgM抗体滴度均低于治疗前（均P〈0．001）。结论：白癜风患并血清抗酪氨酸酶IgG、IgM抗体与疾病活动性和严重程度相关。     

Near-infrared spectroscopy as a potential non-invasive tool in the assessment of disease activity in vitiligo patients

Vitiligo is a common chronic depigmenting skin disease. We explored the utility of near-infrared (NIR) spectroscopy in the identification of spectral changes associated with disease activity in vitiligo patients. In vivo spectral measurements were performed directly on the perilesional skin of 70 vitiligo patients. Relative intensities (second derivative) at 1139, 1344, 1646 and 1839 nm appeared to be significantly lower in the perilesional region of patients with active vitiligo compared with stable disease, while the intensity at 1884 nm seemed to be significantly higher. A classification model based on the spectral ranges around those peaks generated a correct prediction in 82.9% of the cases. In conclusion, we can state that NIR spectroscopy could have potential in the assessment of disease activity. However, large-scale prospective studies are necessary to confirm our preliminary results.     

皮肤镜检查在评估白癜风疾病活动性中的作用

【摘要】 随着皮肤镜研究的不断深入和发展,皮肤镜下毛囊周围色素、皮损边缘、色素网状结构、卫星现象和西米露外观、微Koebner现象和彗星尾部样现象等指标为白癜风疾病活动性评估提供了依据。本文综述近年来皮肤镜在评估白癜风疾病活动性中的研究进展,旨在促进皮肤镜检查在白癜风活动性评估中的应用。     

Serum GDF‐15 level in Behçet's disease: relationships between disease activity and clinical parameters

Growth differentiation factor‐15 (GDF‐15), a member of the transforming growth factor‐β superfamily of cytokines, plays an important role in cell growth, signal transduction, and apoptosis regulation. The aim of this study was to evaluate serum GDF‐15 levels and their relationships with disease‐related variables in patients with Behçet's disease (BD). Forty‐six patients diagnosed with BD and 30 demographically matched healthy control subjects participated in the study. GDF‐15 levels were measured in blood samples from patients and controls. The Behçet's Disease Current Activity Form (BDCAF) was used to evaluate the disease activity of BD. There were no significant differences between the two groups in C‐reactive protein (CRP) level, mean erythrocyte sedimentation rate (ESR), age, body mass index, and mean GDF‐15 levels (P > 0.05). Serum GDF‐15 levels were positively correlated with findings for peripheral arthritis and CRP, and with BDCAF erythema nodosum, BDCAF arthralgia, and BDCAF arthritis scores. Patients with BD were divided into two groups according to the presence of peripheral arthritis; nine subjects (20%) were positive for peripheral arthritis. Serum ESR, CRP, white blood cell counts, and GDF‐15 levels were significantly higher in the group that was positive for peripheral arthritis (P < 0.05). GDF‐15 may play a role in the progression and pathway of Behçet's joint involvement and erythema nodosum that is independent of classic inflammatory response measures.     

Detection of antibodies to melanocytes in vitiligo by specific immunoprecipitation

Immunoprecipitation was used to assay for antibodies to normal human melanocytes in the sera of 12 patients with common vitiligo and 12 normal individuals. The procedure is based on the specific immunoprecipitation using protein A-sepharose of antibodies binding to detergent-soluble, radioiodinated macromolecules of normal human melanocytes grown in culture. Antibodies to melanocytes were found in all 12 patients with vitiligo but in none of the normal sera. None of the sera reacted specifically to normal human fibroblasts or to human melanoma cells radioiodinated in a similar manner. These observations suggest that antibodies to melanocyte-associated antigens are present in common vitiligo.