Involvement of B cells in the development of systemic sclerosis

Systemic sclerosis (SSc) is a rare intractable systemic disease that causes fibrosis and vasculopathy against a background of autoimmune abnormalities. Although the etiology is not yet fully understood, the type of autoantibodies detected in SSc is closely associated with disease severity and prognosis, supporting that those autoimmune abnormalities play an important role in the pathogenesis of SSc. Although the direct pathogenicity of autoantibodies found in SSc is unknown, many previous studies have shown that B cells are involved in the development of SSc through a variety of functions. Furthermore, a number of clinical studies have been conducted in which B-cell depletion therapy has been tried for SSc, and many of these studies have found B-cell depletion therapy to be effective for SSc. However, the involvement of B cells in pathogenesis is complex, as they not only promote inflammation but also play an inhibitory role. This article outlines the role of B cells in the development of SSc, including the latest research

Laser fluorescence as an alternative for digital radiography in detecting caries lesions: a literature review

O diagnóstico das lesões de cárie consiste dos métodos visual/tátil, pelo Sistema Internacional de Detecção e Avaliação de Cárie (Icdas) e radiográfico (BW), no entanto, esses métodos têm limitações para a detecção de cárie em profundidades e localizações diferentes e normalmente são influenciados pela experiência do examinador. Novas tecnologias surgiram para tentar melhorar os métodos de diagnóstico de cárie, entre el as há as que utilizam princípios ópticos para quantificar diferenças entre tecidos saudáveis e desmineralizados, por exemplo: a fluorescência quantitativa induzida pela luz (QLF); a caneta de detecção de cárie “DIAGNOdent”; e o VistaProof (câmera fluorescente). Esta revisão de literatura tem o objetivo de fornecer informações atualizadas sobre a aplicabilidade dos métodos baseados na fluorescência no auxílio de diagnóstico de cáries. Os seguintes resultados são: DIAGNOpen foi o método mais eficaz no diagnóstico de cárie, alguns autores indicam que pode ser utilizado como único método de diagnóstico, no entanto, a maioria recomenda utilizar como método complementar ao Icdas e ao BW. A LFpen deve ser utilizada em associação ao Icdas e dois artigos indicam a transiluminação por luz infravermelha próxima (Nilt) como substituta das BW, embora haja necessidade de mais estudos para chegar a uma decisão concreta. Em conclusão, os métodos digitais para o diagnóstico de cárie são eficientes, mas não substituem os métodos visual/tátil e as radiografias bitewing. Portanto devem ser utilizados como métodos complementares de diagnóstico aos já conhecidos e amplamente utilizados e estudados.Diagnosis of caries lesions consists of visual/tactile methods following the International Caries Detection and Assessment System (ICDAS) and radiographic methods (BW), however these methods have limitations for detecting caries at different depths and locations and is usually influenced by the examiner’s experience. New technologies have emerged to improve caries diagnosis methods, among these are methods that use optical principles to quantify differences between healthy and demineralized tissues, for example: quantitative light- -induced fluorescence (QLF), the “DIAGNOdent” caries detection pen, and VistaProof (fluorescence camera). This literature review aims to provide up-to-date information on the applicability of fluorescence-based methods in the diagnosis of caries. The results show that DIAGNOdent pen was the most effective method for diagnosing caries, wherein some authors indicate that it can be used as the only diagnostic method, but most recommend using it as a complementary method to ICDAS and BW. LFpen must be used in association with ICDAS and 2 articles indicate near-infrared light transillumination (NILT) as a substitute for BW, however there is still a need for further studies to reach a concrete decision. In conclusion, digital methods for the diagnosis of caries are efficient, but they do not replace visual/tactile methods and bitewing radiographs. Therefore, they should be used as a complementary diagnostic method to those already known and widely used and studied

Comprehensive autoantibody profiling in systemic autoimmunity by a highly-sensitive multiplex protein array

Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM

A portable dermatoscope for easy, rapid examination of periungual nailfold capillary changes in patients with systemic sclerosis.

Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenic role. The presence of nailfold capillary abnormalities is useful in diagnosing SSc. Capillaroscopy, however, usually requires special equipment and may be time consuming. Dermatoscope has been presented as a new diagnostic tool for quick and efficient examination of nailfold capillaries for circumstances when standard microscope equipment is not available. To assess the practical utility of dermatoscope for assessment of capillary morphology in patients with SSc, 83 Japanese patients with SSc (68 women, 15 men) and 68 healthy controls were examined in the study. Twenty-one patients (16 women, 5 men) had diffuse cutaneous SSc and 62 (52 women, 10 men) had limited cutaneous SSc. Enlarged capillaries and hemorrhages were evaluated in all 10 fingers with either naked eyes or DermLite((R)) DL100 dermatoscope. Enlarged capillaries and hemorrhages were significantly more frequently detected with dermatoscope than without it. These findings were observed most frequently in the fourth finger. The presence of two or more enlarged capillaries in one or more fingers showed 83.1% sensitivity and 100% specificity for SSc. Among patients with SSc with anti-topoisomerase I antibody, the disease duration correlated negatively with the dermatoscopic number of enlarged capillaries and hemorrhages. Dermatoscope allows the easy and rapid identification of capillary nailfold morphological changes in SSc and should be routinely used for diagnosing SSc.The original publication is available at www.springerlink.co

Perspective to precision medicine in scleroderma

Systemic sclerosis (SSc) is a rare and heterogeneous disease with no relevant environmental trigger or significant responsible gene. It has been and will continue to be difficult to identify large enough patients to conduct classic population-based epidemiologic exposure/non-exposure studies with adequate power to ascertain environmental and genetic risk factors for these entities. The complexity of pathogenesis and heterogeneity are likely to require personalized/precision medicine for SSc. Since several potential drugs are currently available for specific patients if not whole SSc, classification of SSc seems to form the foundation for a better therapeutic strategy. To date, SSc has been classified based on the extent/severity of the affected area as well as some disease markers, including the autoantibody profile. However, such an analysis should also lead to improvements in the design of appropriately stratified clinical trials to determine the effects and prediction of targeted therapies. An approach based on drug response preclinically conducted using patients’ own fibroblasts in vitro, can provide a precise disease marker/therapeutic selection for clinical practice. Because scleroderma dermal fibroblasts have a persistent hyper-productive phenotype occurring not only in person, but also in cell culture conditions. Thus, an accumulating approach based on disease markers ensures progression and de-escalation to re-establish a better life with a personally optimized drug environment after the onset of SSc

CCL13 is a promising diagnostic marker for systemic sclerosis.

Summary Background Previous studies suggest that CCL13 may have some role in the pathogenesis of systemic sclerosis (SSc). Objectives To determine serum levels of CCL13 and its clinical associations in patients with SSc. Methods Serum CCL13 levels were examined by enzyme-linked immunosorbent assay in 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), 20 patients with dermatomyositis (DM), 29 patients with atopic dermatitis (AD) and 50 healthy individuals. Results Mean +/- SD serum CCL13 levels were elevated in patients with SSc (81.3 +/- 55.8 pg mL(-1)) compared with healthy controls (15.0 +/- 9.9 pg mL(-1); P < 0.001) and patients with SLE (22.0 +/- 6.9 pg mL(-1); P < 0.001), DM (24.4 +/- 36.1 pg mL(-1); P < 0.001) and AD (18.0 +/- 6.4 pg mL(-1); P < 0.001). Among patients with SSc, there were no differences in serum CCL13 levels between limited cutaneous SSc and diffuse cutaneous SSc. In a longitudinal study, CCL13 levels were generally unchanged during the follow-up. Conclusions Serum CCL13 was specifically increased in patients with SSc, but not in patients with SLE, DM or AD or in healthy controls. CCL13 could be a promising serological marker for SSc

Effect of extracted garlic powder ingestion for two months on exercise-induced immunological responses

Introduction. Exhaustive exercise is associated with an increased risk of upper respiratory tract infection. Previously, allicin supplementation has been reported to reduce the incidence of common cold symptoms and production of exercise-induced interleukin (IL)-6. However, it is not clear if daily ingestion of the edible portion of whole garlic (Allium sativum) alters the exercise-induced immunological response. The present study investigated the effects of extracted garlic powder ingestion for 2 months on immune cell counts, natural killer cell activity (NKCA), as well as changes in cytokines, cortisol, and lactic acid in response to high-intensity cycling exercise. Methods. The present study employed a before-after study design. Six sedentary male participants (age, 22.0±0.3 years) consumed extracted garlic powder for 2 months, and underwent 45 minutes of cycling exercise at 80% of the heart rate reserve once before and once after the supplementation period. A thousand milligrams of extracted garlic powder, comparable to 6 g (1 clove) of raw garlic, was ingested every day. Blood samples were obtained at the following five time points: before exercise, 0 min, 30 min, 60 min, and 120 min after exercise. We measured NKCA, leukocyte counts, neutrophil counts, lymphocyte counts, as well as levels of serum IL-6, IL-10, cortisol, and lactic acid. Repeated measures ANOVA was used for statistical analyses. When interaction effects were significant, measurement values at the various time points were compared between pre- and post-supplementation period using the paired t-test. Changes were deemed statistically significant when p\u3c0.05. Results. We observed no significant difference in pre-exercise measurements between pre- and post-supplementation periods. In addition, we found no significant interaction effect for leukocytes, neutrophils, NKCA, IL-10, and cortisol. However, we did identify a significant interaction effect for lymphocytes, IL-6, and lactic acid (p=0.033, p=0.030, and p\u3c0.001, respectively). Lymphocyte counts were significantly lower post-supplementation relative to pre-supplementation immediately after exercise (p=0.014). In addition, IL-6 was significantly lower post-supplementation relative to pre-supplementation immediately and 30 minutes after exercise (p=0.015 and p=0.018, respectively). Lactic acid levels were significantly lower post-supplementation relative to pre-supplementation immediately after exercise (p=0.018). Conclusions. The extracted garlic powder did not significantly influence exercise-induced responses by leukocytes, neutrophils, NKCA, IL-10, or cortisol. However, exercise-induced responses by lymphocytes, IL-6, and lactic acid were suppressed after ingestion of extracted garlic powder. Thus, daily ingestion of the edible portion of whole garlic may suppress exercise-induced immunological responses and lactic acid levels

Low zone tolerance requires ICAM-1 expression to limit contact hypersensitivity elicitation.

Painting subsensitizing doses of contact sensitizers on skin (low-dose tolerization) induces antigen (Ag)-specific tolerance, known as low zone tolerance (LZT), which has been experimentally demonstrated by the inhibition of contact hypersensitivity (CHS). Although LZT resulted from the inhibition of the sensitization phase, the effects on the effector/elicitation phase remain unknown. L-selectin and ICAM-1 regulate leukocyte influx into inflamed tissues during the elicitation phase of CHS. LZT was investigated in mice lacking either L-selectin or ICAM-1 to evaluate the roles these leukocyte receptors play in LZT during the elicitation phase. Low-dose tolerization effectively suppressed CHS in wild-type and L-selectin-deficient mice, but not in ICAM-1-deficient mice. Low-dose-tolerized ICAM-1-deficient splenocytes effectively suppressed the elicitation phase in naive wild-type recipients. Sensitized ICAM-1-deficient splenocytes showed normal proliferative responses to the sensitizing Ag and generated normal CHS in wild-type recipients. Thus, ICAM-1 deficiency did not affect sensitization. LZT was associated with a lack of ICAM-1 upregulation after elicitation, suggesting a potentially mechanistic role for ICAM-1. The blockade of IL-10, a possible mediator of LZT, produced by hapten-specific suppressor cells, abrogated LZT and restored ICAM-1 upregulation. These results indicate that low-dose tolerization controls CHS by abrogating ICAM-1 upregulation during the elicitation phase

The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity.

Sensitization and challenge using DNFB induce contact hypersensitivity (CHS) with predominant type 1 helper (Th1) cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. CHS results from inflammatory cell infiltration, a process that is highly regulated by the expression of multiple adhesion molecules. We attempted to determine the role of L-selectin and ICAM-1 in Th1- and Th2-type CHS induced by DNFB or FITC in mice lacking either L-selectin, ICAM-1, or both. Th1-type CHS induced by DNFB was inhibited by L-selectin and/or ICAM-1 deficiency, which was associated with reduced IFN-gamma expression. Similarly, Th2-type CHS induced by FITC was inhibited by L-selectin deficiency. However, Th2-type CHS was increased by ICAM-1 deficiency and accompanied by increased Th2 cytokine expression. Infiltration of in vitro-generated Th1 cells into the FITC-challenged skin decreased in ICAM-1-deficient mice, whereas in vitro-generated Th2 cell infiltration increased, suggesting that ICAM-1 mediates Th1 cell migration and that in the absence of ICAM-1, Th1 cell recruitment decreased, whereas relative Th2 cell migration increased. These results suggest that ICAM-1 mediates Th1 cell recruitment irrespective of DNFB or FITC and that L-selectin recruits Th1 cells in Th1-type CHS, whereas it recruits Th2 cells in Th2-type CHS