Elevated soluble CD23 levels in the sera from patients with localized scleroderma

Soluble CD23 (sCD23) is closely related to B-cell activation and elevated serum levels of sCD23 have been reported in several autoimmune disorders. This study investigated the serum levels of sCD23 and determined the correlation of sCD23 with other immunologic abnormalities and clinical features in localized scleroderma. We examined 49 serum samples by an enzyme-linked immunosorbent assay in the following three subgroups: 15 patients with generalized morphoea, 22 with linear scleroderma, and 12 with morphoea. The serum levels of sCD23 were significantly elevated in patients with localized scleroderma, compared with those in healthy individuals. Of the three subgroups of localized scleroderma, patients with generalized morphoea had the highest levels of serum sCD23. The frequency of IgM antihistone antibody (AHA) and IgM rheumatoid factor (RF), the number of linear lesions, and the frequency of muscle involvement were significantly higher in patients with elevated sCD23 levels than in those with normal levels of sCD23. A significant correlation between the serum sCD23 level and the number of involved areas of the body was observed. Our data suggest that the activation of virgin B cells, which is reflected by elevated sCD23 levels, is closely associated with the production of IgM autoantibodies in localized scleroderma and furthermore that the serum levels of sCD23 are a new serological indicator of the severity of localized scleroderma.     

Soluble CD4 and CD8 in serum from patients with localized scleroderma

Localized scleroderma has been shown to be accompanied by various immunologic abnormalities. To obtain functional information on activated CD4+ or CD8+ T cells, we studied the levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum from patients with localized scleroderma. Serum samples were examined by enzyme-linked immunosorbent assay. The samples were obtained from 49 patients in the following three subgroups: 15 patients with generalized morphea, 22 with linear scleroderma, and 12 with morphea. The levels of sCD4 and sCD8 were significantly elevated in patients with generalized morphea. Furthermore, these patients showed significantly higher levels of sCD4 than those with systemic sclerosis (SSc). The frequency of positivity for IgG anti-single-stranded DNA (ssDNA) antibody was significantly higher in localized scleroderma patients with elevated sCD4 levels than in patients with normal sCD4 levels. The frequency of positivity for antinuclear antibodies, IgM antihistone antibodies, IgG anti-ssDNA antibody and rheumatoid factor, and elevated sCD23 levels were significantly higher in localized scleroderma patients with elevated sCD8 levels than in patients with normal sCD8 levels. Our findings suggest that both CD4+ and CD8+ T cells are activated in vivo in generalized morphea and that the immunologic events in generalized morphea are different from those in SSc.     

Serum levels of soluble IL-2 receptor, soluble ICAM-1, TNF-alpha, interleukin-4 and interleukin-6 in scleroderma

Background A variety of immunological markers have been reported to be elevated in patients with systemic scleroderma (SSc). Objective The aim of this study was to determine which of the following parameters: soluble IL-2 receptor (sIL-2r). soluble ICAM-1 (sICAM-1), tumour necrosis factor (TNF-alpha), interleukin-6 (IL-6) and interleukin-4 (IL-4) reflect the clinical stage of the disease and how they correlate with each other. Methods In 31 scleroderma patients the serum levels of these markers were measured in the same blood sample using ELISA test kits. The results were correlated with clinical findings such as extent of skin disease, inflammatory disease activity and involvement of internal organs. Results SIL-2r, slCAM-1 and TNF-alpha showed significant differences in subgroups of SSc patients in contrast to IL-4and IL-6, The five parameters did not correlate with each other. Conclusion sIL-2r, sICAM-1 and TNF-alpha showed differences in subgroups of scleroderma and therefore they may be useful in further studies as markers of disease activity.     

Autoantibodies against matrix metalloproteinase-1 in patients with localized scleroderma

BACKGROUND: Localized scleroderma (LSc) is characterized by cutaneous fibrosis and various autoantibodies. OBJECTIVE: To determine the presence or levels of antibodies (Abs) against matrix metalloproteinase (MMP)-1 and their clinical relevance in LSc. METHODS: Anti-MMP-1 Ab was examined by ELISA (Enzyme-Linked ImmunoSorbent Assay) and immunoblotting using human recombinant MMP-1. MMP-1 collagenase activity was determined using biotinylated collagen as substrate and the amount of cleaved biotinylated fragments of collagen by MMP-1 was measured by ELISA. RESULTS: LSc patients exhibited significantly elevated IgG anti-MMP-1 Ab levels relative to normal controls at similar level of patients with systemic sclerosis (SSc). However, IgG anti-MMP-1 Ab levels were comparable among the 3 LSc subgroups: morphea, linear scleroderma, and generalized morphea. When absorbance values higher than the mean+2S.D. of normal controls were considered positive, IgG or IgM anti-MMP-1 Ab was found in 46% and 49% of total LSc patients and SSc patients, respectively. Anti-MMP-1 Ab was detected most frequently in morphea patients (60%), followed by linear scleroderma patients (47%) and then generalized morphea patients (25%). LSc patients positive for IgG anti-MMP-1 Ab had elevated levels of IgG anti-single-stranded DNA Ab, IgG anti-nucleosome Ab, and shorter disease duration relative to those negative. The presence of anti-MMP-1 Ab in LSc patients was confirmed by immunoblotting. IgG isolated from LSc patients' sera positive for IgG anti-MMP-1 Ab by ELISA inhibited MMP-1 collagenase activity. CONCLUSION: These results suggest that anti-MMP-1 autoantibody is a novel autoantibody in LSc.     

Stimulated expression of decorin and the decorin gene in fibroblasts cultured from patients with localized scleroderma

Decorin mRNA levels, the content of decorin and the synthesis of dermatan sulphate in skin fibroblasts from patients with systemic and localized scleroderma were investigated. Approximately a 2.2-fold increase in decorin mRNA levels, was found by Northern blot analysis in localized scleroderma, but no significant changes were found in systemic scleroderma. Decorin, as measured by an immunoblot assay, was increased 2.6-fold in fibroblast cultures from localized scleroderma but not in those from systemic scleroderma. In contrast, the synthesis of dermatan sulphate was similar in both conditions. These results indicate that altered decorin gene expression causes abnormal proteoglycan metabolism in localized scleroderma.     

Presence of eosinophilia in progressive systemic sclerosis and localized scleroderma

Summary Recent studies on eosinophilic fasciitis have lead to this investigation of eosinophilia in progressive systemic sclerosis and localized scleroderma.Eosinophilia (eosinophilic count >300/cmm) was found in ten of 63 progressive systemic sclerosis patients (15.8%) and in two of nine localized scleroderma cases (22.2%). In patients with progressive systemic sclerosis eosinophilia was found occasionally in six cases; it was transitory, but frequent in three cases; it was constant and very high in one case. In patients with localized scleroderma eosinophilia was found occasionally in one case and frequent, but not constant, in the other one.The possible influence of drugs could be excluded in five cases: three progressive systemic sclerosis cases and two affected with localized scleroderma.Therefore, it is possible to confirm that eosinophilia is not a distinctive sign of eosinophilic fasciitis in patients suffering from scleroderma-like syndromes.While eosinophilia is related to inflammation in eosinophilic fasciitis, eosinophilia and disease activity could not be correlated in our patients with PSS.Recently, it has been suggested that eosinophilia might be an unfavorable prognostic criterion in progressive systemic sclerosis. Our data does not allow confirmation of this assumption.     

Autoantibodies to the heat-shock protein hsp73 in localized scleroderma

We determined the presence of antibodies to the heat-shock protein hsp73 (anti-hsp73) in 57 serum samples from patients with localized scleroderma using an enzyme-linked immunosorbent assay (ELISA). In addition, 30 samples from healthy individuals, 30 from patients systemic lupus erythematosus (SLE) and 32 from patients with systemic sclerosis were assessed. IgG and/or IgM anti-hsp73 antibodies were detected in 33% (19/57) of the patients with localized scleroderma. Among the three subtypes of localized scleroderma, generalized morphoea showed the highest incidence of anti-hsp73 antibodies (40%, 6/15). IgG and/or IgM anti-hsp73 antibodies were also detected in 9/30 samples (30%) from patients with SLE and in 13/32 samples (41%) from patients with systemic sclerosis, while the samples from the healthy controls were all negative for anti-hsp73. By immunoblotting, specific binding of antibodies to hsp73 was confirmed with representative serum samples that were positive for anti-hsp73 in the ELISA. Our findings indicate that the presence of anti-hsp73 is an additional immunological abnormality in localized scleroderma.     

Radiation-induced localized scleroderma in breast cancer patients

Radiation-induced scleroderma in breast cancer patients appears to occur in approximately one out of every 500 patients. We report four cases that developed within 3 months of conservative breast surgery and postoperative radiation treatment. The reaction was contained entirely within the treatment field and demonstrated the typical features of this condition where the breast becomes erythematous, violaceous, indurated, retracted, and progressively pigmented. The breast tends to soften and become more comfortable over 1–4 years; however, significant induration, retraction and pigmentary changes remain. There appears to be no predictive factors. Radiation-induced scleroderma must be differentiated from cellulitis and recurrent breast cancer.     

白癜风患者黑素细胞移植的疗效与白介素6、可溶性白介素6受体水平的关系

【摘要】 目的 探讨白介素6（IL-6）、可溶性白介素6受体（sIL-6R）与白癜风患者自体培养黑素细胞移植疗效的关系。 方法 对53例稳定期白癜风患者进行自体培养黑素细胞移植,收集白斑区与非白斑区的疱液,移植后6个月观察疗效,用ELISA的方法测定白癜风患者皮肤组织液中IL-6及sIL-6R水平,比较移植成功组与失败组白斑区及非白斑区组织液中IL-6及sIL-6R水平。 结果 白癜风患者白斑区IL-6（113.22 ± 81.20） ng/L与非白斑区（84.40 ± 48.78） ng/L,及白斑区sIL-6R（56.28 ± 24.87） ng/L和非白斑区（53.96 ± 25.67） ng/L配对比较,差异有统计学意义。移植失败组与成功组比较：白斑区IL-6（153.61 ± 100.26） ng/L的浓度明显高于移植成功组（88.75 ± 55.75） ng/L（P < 0.05）;非白斑区浓度（100.26 ± 55.17） ng/L与（74.78 ± 42.50） ng/L比较,差异无统计学意义,两组之间sIL-6R的浓度比较,差异均无统计学意义。稳定时间 < 1年的白斑区IL-6（148.46 ± 88.00） ng/L与非白斑区（114.82 ± 64.66） ng/L均高于稳定时间 ≥ 1年的白斑区（93.54 ± 71.07） ng/L与非白斑区（67.40 ± 25.23） ng/L（P < 0.05）,而sIL-6R比较,差异无统计学意义。节段型白斑区IL-6（77.33 ± 61.70） ng/L明显低于非节段型（131.68 ± 84.54） ng/L（P < 0.05）,非白斑区IL-6及sIL-6R的组间比较,差异均无统计学意义。非节段型患者的移植成功组非白斑区IL-6（78.25 ± 40.30） ng/L、白斑区（96.27 ± 53.390） ng/L与失败组非白斑区（107.02 ± 42.48） ng/L、白斑区（178.90 ± 96.48） ng/L比较,差异均有统计学意义,sIL-6R在两组间比较,差异无统计学意义。 结论 IL-6在组织液中的异常表达对白癜风患者皮损区的微环境改变有一定的影响,可能与自体黑素细胞移植疗效相关。     

Comparative biochemistry of human skin: glycosaminoglycans from different body sites in normal subjects and in patients with localized scleroderma

OBJECTIVES: The aim of this investigation is to compare the relative proportions of disaccharides of chondroitinase-digestible glycosaminoglycans (GAGs) among the different body sites in control human skin and in the skin lesions of patients with localized scleroderma. METHODS: The disaccharide relative proportions were determined using high-performance liquid chromatography (HPLC). RESULTS: DeltaDi-4S, the main disaccharide unit of dermatan sulphate (DS), was the major skin GAG disaccharide (approximately 70% of the total) in control skin among all different body sites studied here. In scleroderma there was an increase in the relative proportion of both deltaDi-HA, the main disaccharide unit of hyaluronic acid (HA), and deltaDi-diS(B) (alpha-deltaUA(2SO4)-1-->3-GalNAc(4SO4)), derived from DS, and a decrease in deltaDi-4S, as compared with the uninvolved skin or the site-matched control skin. CONCLUSION: DS is the major GAG species in normal skin from different body sites. In addition, our results suggest a decrease and also a structural change in DS and an increase in the proportion of HA in scleroderma skin.     

In situ expression of messenger RNA of interleukin-1 and interleukin-6 in psoriasis: interleukin-6 involved in formation of psoriatic lesions

Summary Psoriasis is a disease of abnormal proliferation and differentiation of epidermal cells. Several cytokines released by keratinocytes are implicated as factors responsible for this pathological condition of the epidermis. In order to elucidate the role of these cytokines in psoriasis, messenger RNA (mRNA) expression of interleukin-1 (IL-1) and IL-6 in psoriatic epidermis was investigated using biotin-labelled complementary DNA (cDNA) of the cytokines. Messenger RNA of IL-1 was weakly detected in some normal healthy epidermis specimens and more strongly in all the perilesional uninvolved psoriatic epidermis specimens. It was also expressed in the transitional zone between uninvolved and fully developed psoriatic skin, but was not expressed in lesional skin. In contrast, IL-6 mRNA was rarely expressed in normal healthy epidermis, but was expressed in perilesional uninvolved psoriatic epidermis, in the transitional zone and in the fully developed lesional epidermis, with the maximum intensity in the transitional zone. Expression of mRNA of IL-6 receptor showed a similar tendency to that of IL-6. It was expressed in psoriatic epidermis, most strongly in the transitional zone, but not in normal healthy epidermis. IL-6 was demonstrated immunohistochemically in psoriatic epidermis, but IL-6 receptor was demonstrated only in the transitional zone. Thus IL-6 and its receptor expression correlated well with the formation of psoriatic lesions where IL-1 may initiate their expression. IL-6 may play an important role in the pathogenesis of psoriasis.     

Measurement of transepidermal water loss in localized scleroderma

Localized scleroderma (LS) is a disease characterized by fibrotic changes in the dermis. Connective tissue growth factor and transforming growth factor β2 are the main mediators of fibrogenesis; this, along with excessive connective tissue production, affects epidermal keratinocytes, and thereby contributes to the changed quality of skin barrier. The objective of this article was to study the objective measurement of the skin barrier quality in LS with transepidermal water loss (TEWL) meter. The measurements of TEWL were performed on LS plaques in all three stages of various body locations. Control measurements were made on the contralateral side of healthy skin. The difference between TEWL in LS area and the contralateral side of the healthy skin was evaluated. A higher average TEWL 7.86 g/m²/h (SD 5.29) was observed on LS plaques compared with the control measurements on healthy skin 6.39 g/m²/h (SD 2.77). TEWL average values decreased from the inflammatory stage, through the sclerotic and to the atrophic stage. The mean difference 1.301 g/m²/h (SD 5.16) was found between TEWL on LS plaques and on the contralateral healthy skin in 82 measurements, i.e., a higher TEWL was observed in LS. The difference was statistically significant with p = 0.0250. Although fibrogenesis in scleroderma is localized in dermis, the skin barrier changes can be detected.     

Case of localized scleroderma associated with osteomyelitis

We report a 4-year-old girl presenting with progressive linear scleroderma affecting the right leg. Biopsy specimen disclosed typical histopathological findings of localized scleroderma. Right leg magnetic resonance imaging (MRI) showed high signal areas on T₂-weighted images on the subcutaneous fatty tissue, muscles and bone marrow, suggesting that skin inflammation extended to the bone marrow. Oral corticosteroid therapy was instituted with improvement of both skin sclerosis and MRI findings. Our observations suggest that MRI examination should be considered in patients with localized scleroderma to evaluate the extension of the inflammation.     

Adiponectin expression is decreased in the involved skin and sera of diffuse cutaneous scleroderma patients

In this study, we determined the adiponectin expression in the serum and lesional skin of patients with scleroderma (SSc). Serum adiponectin concentrations were measured in 32 patients with SSc, 10 patients with SLE, 12 patients with dermatomyositis patients and 13 healthy subjects with specific enzyme-linked immunosorbent assays. Adiponectin mRNA was determined in skin tissues of five patients with diffuse cutaneous SSc (dcSSc), seven patients with limited cutaneous SSc (lcSSc) and seven healthy subjects with real-time polymerase chain reaction. There was a significant reduction in serum adiponectin levels in patients with dcSSc. SSc patients with decreased serum adiponectin levels had higher total skin thickness score and higher incidence of pulmonary fibrosis. Adiponectin mRNA levels in skin tissues from patients with dcSSc were also reduced. Serum adiponectin levels may be a useful biomarker for fibrotic condition in patients with SSc. Clarifying the role of adiponectin in collagen diseases may lead to further understanding of the pathogenesis and new therapeutic approach.     

系统性红斑狼疮患者外周血白介素2和白介素6及其受体的研究

目的 探讨白介素2(IL-2)、白介素6(IL-6)及其受体在系统性红斑狼疮(SLE)患者治疗前后的变化及其意义.方法 采用酶联免疫吸附法和免疫荧光标记流式细胞仪检测技术对SLE患者治疗前后和正常人外周血IL-2和IL-6及其受体水平进行测定分析.结果 ①SLE患者IL-2水平显著低于正常人对照(P<0.05),而sIL-2R、IL-6、sIL-6R均显著增高;②SLE患者sIL-2R、IL-6、sgp80与SLE病情活动指数(SLEDAI)呈显著正相关;③SLE患者治疗后sIL-2R和sgp80水平与治疗前相比,差异均有显著性.结论 IL-2、IL-6及其受体是参与SLE免疫病理机制的重要细胞因子,其中sIL-2R、IL-6及sgp80与病情活动性密切相关,sIL-2R、sgp80对判断疗效可能具有重要意义.