RESUMO
BACKGROUND: Currently, the mainstream treatments for systemic lupus erythematosus (SLE) are based on glucocorticoids and immunosuppressants, which are known to have considerable adverse effects. This meta-analysis is aimed at confirming the efficacy and safety of acupuncture therapy in combination with traditional medications in the treatment of SLE. METHODS: Multiple databases were searched for randomized controlled trials using acupuncture therapy in combination with conventional pharmacotherapy for the treatment of SLE, from the establishment of the database to March 2023. Study selection, data collection, as well as quality assessment were conducted by 2 reviewers independently. RevMan 5.4 and Stata 17 software were used for Meta-analysis. RESULTS: Seven eligible studies involving 514 patients with SLE were included. Meta-analysis demonstrated that in SLE patients, extra treatment with acupuncture was superior to drug therapy alone in improving the overall response rate (RR = 1.20, 95% confidence intervals [1.11, 1.29], P < .00001, heterogeneity P = .69, I2 = 0%) and regulating immunological indicators (C3, C4, IgG, T lymphocyte subpopulation, IL-6, ds-DNA, ESR) while reducing TCM symptom scores, the SLE Disease Activity Index (SLEDAI) and the incidence of adverse events on treatment (P ≤ 0.05). Additionally, it was able to reduce BUN, Scr and 24 hours urine protein, suggesting that acupuncture treatment had a protective effect on the kidneys. CONCLUSIONS: Acupuncture therapy combined with conventional pharmacotherapy is an efficient and safe way in the treatment of SLE. However, the conclusions drawn from this meta-analysis have some limitations due to the small number and uneven quality of the included studies, leading to heterogeneity and bias. Thus more relevant high-quality randomized controlled trials are needed for further evaluation in the future.
Assuntos
Terapia por Acupuntura , Lúpus Eritematoso Sistêmico , Humanos , Terapia por Acupuntura/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etiologia , Imunossupressores/uso terapêuticoRESUMO
Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal and immune health, and to summarize the mechanistic, epidemiological, and clinical evidence on the relationship between vitamin D and rheumatic diseases. Multiple observational studies have demonstrated the association between a low level of serum 25-hydroxyvitamin D [25(OH)D] and the presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies, and osteoarthritis (OA). Nevertheless, the specific benefits of vitamin D supplements for the treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for the improvement of disease activity of RA, SLE, and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently than others, as inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain a serum 25(OH)D level of at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis, and fracture, and possibly 40-60 ng/mL (100-150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.
Assuntos
Suscetibilidade a Doenças , Doenças Reumáticas/etiologia , Doenças Reumáticas/metabolismo , Vitamina D/metabolismo , Biomarcadores , Gerenciamento Clínico , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/metabolismo , Redes e Vias Metabólicas/efeitos da radiação , Músculo Esquelético/metabolismo , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Luz Solar , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicaçõesRESUMO
The paradigm that autoimmune diseases are abberations in the adaptive immune system is over 50 years old, but recent data suggest a multitude of abnormalities in the innate immune system in lupus and other autoimmune diseases. This viewpoint elaborates the reasons that I think it is time to reexamine this paradigm and shift our research focus to the innate immune system in lupus and other prototypic autoimmune diseases.
Assuntos
Doenças Autoimunes , Inflamação , Imunidade Adaptativa/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Feminino , Humanos , Imunidade Inata/imunologia , Inflamação/etiologia , Inflamação/imunologia , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/imunologia , MasculinoRESUMO
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.
Assuntos
Comunicação Celular , Exossomos/fisiologia , Rim/patologia , Lúpus Eritematoso Sistêmico/etiologia , MicroRNAs/fisiologia , Adulto , Regulação para Baixo , Exossomos/química , Feminino , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/classificação , Masculino , MicroRNAs/sangue , Adulto JovemAssuntos
Lúpus Eritematoso Sistêmico/metabolismo , Oxidiazóis/farmacologia , Propilenoglicóis/farmacologia , Receptores de Esfingosina-1-Fosfato/metabolismo , Animais , Biomarcadores , Microambiente Celular/efeitos dos fármacos , Microambiente Celular/genética , Microambiente Celular/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos MRL lpr , Terapia de Alvo Molecular , Plasmócitos/efeitos dos fármacos , Plasmócitos/imunologia , Plasmócitos/metabolismo , Pesquisa Translacional BiomédicaRESUMO
Objectives Hypoparathyroidism is a rare disease in children that occurs as a result of autoimmune destruction of the parathyroid glands, a defect in parathyroid gland development or secondary to physical parathyroid gland disturbance. Typical symptoms of hypoparathyroidism present as hypocalcaemia and hyperphosphatemia due to decreased parathyroid hormone secretion and may lead to nerve and muscles disturbances resulting in clinical manifestation of tetany, arrhythmias and epilepsy. Currently, there is no conventional hormone replacement treatment for hypoparathyroidism and therapeutic approaches include normalising mineral levels using an oral calcium supplement and active forms of vitamin D. Case presentation We present the case of a 10-year-old girl with primary hypoparathyroidism who had no prior history of autoimmune disorders, but who subsequently developed systemic lupus erythematosus.
Assuntos
Hipoparatireoidismo/complicações , Lúpus Eritematoso Sistêmico/patologia , Cálcio/administração & dosagem , Criança , Suplementos Nutricionais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etiologia , Prognóstico , Vitamina D/administração & dosagem , Vitaminas/administração & dosagemRESUMO
Inhalation of crystalline silica (cSiO2) in the workplace is etiologically linked to lupus and other autoimmune diseases. Exposing lupus-prone NZBWF1 mice to respirable cSiO2 unleashes a vicious cycle of inflammation and cell death in the lung that triggers interferon-regulated gene expression, ectopic lymphoid structure (ELS) development, elevation of local and systemic autoantibodies (AAbs), and glomerulonephritis. However, cSiO2-induced inflammation and onset of autoimmunity can be prevented by inclusion of the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) into the diet of these mice. Since cSiO2 both causes cell death and interferes with efferocytosis, secondary necrosis of residual cell corpses might provide a rich and varied autoantigen (AAg) source in the lung. While it is known that the particle induces anti-nuclear and anti-dsDNA AAbs in NZBWF1 mice, the full extent of the cSiO2-induced AAb response relative to specificity and isotype is not yet understood. The purpose of this study was to test the hypotheses that cSiO2 exposure induces a wide spectrum of AAbs in the pulmonary and systemic compartments, and that dietary DHA intervention prevents these changes. Archived tissue fluid samples were obtained from a prior study in which NZBWF1 mice were fed purified isocaloric diets containing no DHA (control) or DHA corresponding calorically to human doses of 2 and 5 g/day. Mice were intranasally instilled with 1 mg cSiO2 or saline vehicle weekly for 4 weeks, then groups euthanized 1, 5, 9, or 13 weeks post-instillation (PI) of the last cSiO2 dose. Bronchoalveolar lavage fluid (BALF) and plasma from each time point were subjected to AAb profiling using a microarray containing 122 AAgs. cSiO2 triggered robust IgG and IgM AAb responses against lupus-associated AAgs, including DNA, histones, ribonucleoprotein, Smith antigen, Ro/SSA, La/SSB, and complement as early as 1 week PI in BALF and 5 weeks PI in plasma, peaking at 9 and 13 weeks PI, respectively. Importantly, cSiO2 also induced AAbs to AAgs associated with rheumatoid arthritis (collagen II, fibrinogen IV, fibrinogen S, fibronectin, and vimentin), Sjögren's syndrome (α-fodrin), systemic sclerosis (topoisomerase I), vasculitis (MPO and PR3), myositis (Mi-2, TIF1-γ, MDA5), autoimmune hepatitis (LC-1), and celiac disease (TTG). cSiO2 elicited comparable but more modest IgA AAb responses in BALF and plasma. cSiO2-induced AAb production was strongly associated with time dependent inflammatory/autoimmune gene expression, ELS development, and glomerulonephritis. AAb responses were dose-dependently suppressed by DHA supplementation and negatively correlated with the ω-3 index, an erythrocyte biomarker of ω-3 content in tissue phospholipids. Taken together, these findings suggest that cSiO2 exposure elicits a diverse multi-isotype repertoire of AAbs, many of which have been reported in individuals with lupus and other autoimmune diseases. Furthermore, induction of this broad AAb spectrum could be impeded by increasing ω-3 tissue content via dietary DHA supplementation.
Assuntos
Autoanticorpos/imunologia , Autoimunidade , Gorduras na Dieta , Ácidos Graxos Ômega-3/metabolismo , Dióxido de Silício/efeitos adversos , Animais , Autoantígenos/imunologia , Doenças Autoimunes/etiologia , Modelos Animais de Doenças , Isotipos de Imunoglobulinas/imunologia , Lúpus Eritematoso Sistêmico/etiologia , Camundongos , Doenças Profissionais/etiologia , Exposição OcupacionalRESUMO
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving a dysregulated immune response which ultimately leads to multiple organ failure. Several immunological and cellular checkpoints are available as drug targets. However, the available chemosynthetic drugs such as non-steroidal anti-inflammatory drugs and corticosteroids provide limited therapy with extreme toxicities. Moreover, the disease heterogeneity in SLE is very difficult to manage by a single drug component. Hence, it is imperative to utilize the holistic capabilities of natural plant products as immunomodulators and intracellular signaling regulators, thereby providing an auxiliary option of treatment. Additionally, the herbal drugs also serve as symptomatic relief providers, thereby serving as a prophylactic remedy in case of cerebrovascular, hepatic, nephropathological, hematological, cardiopulmonary, mucocutaneous and musculoskeletal manifestations of SLE. The present review attempts to showcase the current state of knowledge regarding the utility of plant-derived phyto-metabolites with their probable mechanistic roles in treating SLE, by means of targeting the signaling cascade, proinflammatory cytokine production and B-T cell co-stimulation. It is hoped that further preclinical and clinical studies will be embarked upon in order to understand the underlying therapeutic and mechanistic aspects of these medicinal herbs.
Assuntos
Produtos Biológicos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Metaboloma , Plantas/metabolismo , Animais , Humanos , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , FitoterapiaRESUMO
CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca2+ response via docking of PLCγ1 to the calcium-inducing domain (CID) within CD95. This signaling pathway induces accumulation of inflammatory Th17 cells in damaged organs of lupus patients, thereby aggravating disease pathology. A large-scale screen revealed that the HIV protease inhibitor ritonavir is a potent disruptor of the CD95-PLCγ1 interaction. A structure-activity relationship approach highlighted that ritonavir is a peptidomimetic that shares structural characteristics with CID with respect to docking to PLCγ1. Thus, we synthesized CID peptidomimetics abrogating both the CD95-driven Ca2+ response and transmigration of Th17 cells. Injection of ritonavir and the CID peptidomimetic into lupus mice alleviated clinical symptoms, opening a new avenue for the generation of drugs for lupus patients.
Assuntos
Inflamação/prevenção & controle , Peptidomiméticos/farmacologia , Fosfolipase C gama/metabolismo , Células Th17/efeitos dos fármacos , Receptor fas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etiologia , Masculino , Camundongos Mutantes , Simulação de Acoplamento Molecular , Peptidomiméticos/química , Fosfolipase C gama/genética , Domínios Proteicos , Ritonavir/química , Ritonavir/farmacologia , Relação Estrutura-Atividade , Células Th17/metabolismo , Células Th17/patologia , Tiazóis/química , Tiazóis/farmacologia , Receptor fas/genéticaRESUMO
We aimed to analyze the causal association between coffee consumption and the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods. We used publicly available summary statistics datasets of coffee consumption genome-wide association studies (GWASs) as an exposure variable and RA and SLE GWASs as outcomes. Four single-nucleotide polymorphisms (SNPs) from GWASs of coffee consumption were selected as instrumental variables (IVs) to improve inference: NCARD (rs16868941), POR (rs17685), CYP1A1 (rs2470893), and LAMB4 (rs382140). The IVW method showed a causal association between coffee consumption and RA (beta = 0.770, SE = 0.279, p = 0.006). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = - 0.145, p = 0.451). While the MR-Egger analysis showed no causal association between coffee consumption and RA (beta = 2.744, SE = 1.712, p = 0.355), the weighted median approach demonstrated a causal association between coffee consumption and RA (beta = 0.751, SE = 0.348, p = 0.031). However, the associations based on the weighted median analyses after the Bonferroni correction were not significant (adjusted p values = 0.091). The IVW, MR-Egger analysis, and weighted median methods showed no causal association between coffee consumption and SLE risk (beta = 0.594, SE = 0.437, p = 0.209; beta = 3.100, SE = 3.632, p = 0.550; beta = 0.733, SE = 0.567, p = 0.196). MR analysis results do not support causal associations between coffee consumption and the development of RA and SLE.
Assuntos
Artrite Reumatoide/genética , Café , Lúpus Eritematoso Sistêmico/genética , Análise da Randomização Mendeliana/métodos , Polimorfismo de Nucleotídeo Único , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/etiologia , Estudo de Associação Genômica Ampla , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/etiologiaRESUMO
Systemic lupus erythematosus (SLE) and juvenile SLE (jSLE) are autoimmune disorders naturally associated with several genetic, environmental, hormonal, and immunological contributing factors. It has been assumed that vitamin D deficiency may have a role in the immune activation of patients with SLE and play an active part in many comorbidities and even complications. A host of clinical studies suggested that vitamin D exerts inhibitory effects on many immunological abnormalities associated with SLE, also in children and adolescents, while different reports have hypothesized that vitamin D may be associated with accelerated cardiovascular disease in SLE. This review updates and summarizes the information related to the immunoregulatory effects of vitamin D and its importance in jSLE, discusses the innumerable correlations between vitamin D and disease activity, including clinical expression and gene polymorphisms of vitamin D receptor as well as the recommendations for vitamin D supplementation in these patients. Despite the excitement raised by many data obtained about vitamin D and its influence on several aspects of the disease, further well-designed perspective trials are required to define the exact role that vitamin D may have in the management of both SLE and jSLE.
Assuntos
Suplementos Nutricionais/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/etiologia , Deficiência de Vitamina D/complicações , Adolescente , Feminino , Humanos , Lúpus Eritematoso Sistêmico/patologiaRESUMO
The significant decrease in mortality rates worldwide, the increased proportion of patients achieving a durable remission, and the recent approval of a new drug after several decades are encouraging advances in the tangled history of systemic lupus erythematosus (SLE). However, when data are observed more closely, the research findings on disease pathogenesis and targeted treatments have been quite misleading, as illustrated by the central role of B cells but the missed endpoints in rituximab clinical trials which are burdened by the wide variability of SLE manifestations or the ethnic determinants of disease severity. Other biologic therapies, on the other hand, inhibit B cell stimulating factor BAFF but are proving to be short of revolutionary, not yet overcoming high-dose long-term glucocorticoids still largely used without an agreement on what clinical targets are to be sought in the proposed treat-to-target approach. The large amount of data from genome-wide association studies, the detailed reports on T cell epigenetics, or the numerous established and novel animal models have also proven insufficient to change our understanding of the human disease. Nonetheless, we have now tools for a better and earlier SLE diagnosis, thanks to reliable biomarkers, improved care of kidney involvement, better pregnancy outcomes, while the neuropsychiatric manifestations remain challenging. These advances are well mirrored by some proposed synthetic drugs, such as tacrolimus, or biologics, including IFNα inhibitors and other drugs capable to modulate the immune system. Ultimately, we may foresee that genetic and epigenetic data, along with the variable clinical manifestations represent the bases for SLE to become an ideal candidate for the introduction of truly personalized medicine.
Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/terapia , Medicina de Precisão , Animais , Autoimunidade , Linfócitos B/imunologia , Linfócitos B/metabolismo , Terapia Biológica/métodos , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Epigênese Genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Medicina de Precisão/métodos , Gravidez , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Sheng-ma-bie-jia-tang (SMBJT) is a Traditional Chinese Medicine (TCM) formula that is widely used for the treatment of Systemic Lupus Erythematosus (SLE) in China. However, molecular mechanism behind this formula remains unknown. Here, we systematically analyzed targets of the ingredients in SMBJT to evaluate its potential molecular mechanism. First, we collected 1,267 targets from our previously published database, the Traditional Chinese Medicine Integrated Database (TCMID). Next, we conducted gene ontology and pathway enrichment analyses for these targets and determined that they were enriched in metabolism (amino acids, fatty acids, etc.) and signaling pathways (chemokines, Toll-like receptors, adipocytokines, etc.). 96 targets, which are known SLE disease proteins, were identified as essential targets and the rest 1,171 targets were defined as common targets of this formula. The essential targets directly interacted with SLE disease proteins. Besides, some common targets also had essential connections to both key targets and SLE disease proteins in enriched signaling pathway, e.g. toll-like receptor signaling pathway. We also found distinct function of essential and common targets in immune system processes. This multi-level approach to deciphering the underlying mechanism of SMBJT treatment of SLE details a new perspective that will further our understanding of TCM formulas.
Assuntos
Medicamentos de Ervas Chinesas , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Medicina Tradicional Chinesa , Biologia de Sistemas/métodos , Química Farmacêutica , Biologia Computacional/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Humanos , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/metabolismo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacosRESUMO
El lupus eritematoso sistémico es una enfermedad reumática sistémica enormemente heterogénea, con múltiples posibles manifestaciones de patogenia diversa, como se ilustra en esta revisión sobre las novedades más relevantes concernientes a esta compleja enfermedad autoinmune. Se revisan aspectos como la patogenia de la anemia crónica asociada al lupus eritematoso sistémico, la estimación del riesgo cardiovascular, el síndrome antifosfolipídico, la predicción del daño acumulado y los avances más recientes en el tratamiento, incluyendo los tolerógenos y las terapias biológicas. También se revisan las contribuciones más relevantes en torno a las terapias clásicas, como la optimización del uso de los glucocorticoides y los antipalúdicos, así como el papel que pueda desempeñar la vitamina D (AU)
Systemic lupus erythematosus is a heterogeneous rheumatic systemic disease with extremely varied clinical manifestations and a diverse pathogenesis, as illustrated in this review on the most relevant new knowledge related to the disease. Topics such as anemia, pathogenesis, cardiovascular risk assessment, antiphospholipid syndrome, prediction of damage and recent advances in treatment, including tolerogenic and biological agents, are discussed. Relevant contributions regarding classical therapies such as corticosteroid and antimalarials and their optimal use, as well as the roll of vitamin D, are also referred (AU)
Assuntos
Humanos , Masculino , Feminino , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Fatores de Risco , Síndrome Antifosfolipídica/complicações , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Teratogênicos , Terapia Biológica/métodos , Terapia Biológica , Glucocorticoides/uso terapêutico , Vitamina D/uso terapêutico , Antimaláricos/uso terapêuticoRESUMO
Vitamin D has some well-known effects on calcium, phosphate and bone metabolism, but it has recently shown to have many other effects, which may potentially be relevant to patients with extra-skeletal rheumatic diseases. Such effects may be justified by: 1) the presence of the vitamin D receptors also on extra-osseous cells, such as cartilage cells, sinoviocytes, muscle cells; 2) the proven role of vitamin D in the control of the transcription of genes involved in rheumatic diseases; 3) the evidence that vitamin D has multiple endocrine effects not only on calcium homeostasis; 4) the activation of vitamin D not only in the kidneys, but also in monocyte-macrophage and lymphocytic cell lines and in some epithelial cells with additional intracrine and paracrine effects. Vitamin D deficiency has been reported in numerous metabolic, degenerative, inflammatory and autoimmune rheumatic diseases. In some cases this association was also related to the risk of developing a rheumatic disease or the degree of disease activity. However there is no conclusive evidence of the efficacy of a preventive or therapeutic strategy based on vitamin D supplementation in extra-skeletal rheumatic diseases. This review aims to provide an overview of the latest evidence concerning the relationship between vitamin D and the most relevant rheumatic diseases.
Assuntos
Doenças Reumáticas/etiologia , Deficiência de Vitamina D/complicações , Artrite Reumatoide/etiologia , Humanos , Lúpus Eritematoso Sistêmico/etiologia , Doenças Musculares/etiologia , Osteoporose/etiologia , Doenças Reumáticas/tratamento farmacológico , Vitamina D/fisiologia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
A ten-year (December 1992 - December 2002) evaluation of 225 pediatric bronchoalveolar lavage (BAL) differential cell counts showed appearance of the cells corresponding to the cytological entity - lupus erythematosus cell (LEC) in 47 specimens of which not a single case was associated with the coexistent autoimmune disease. There was a significant increase in the percentage of LEC in BAL samples of the examinees during the first 6 months after the bombing of targets in Serbia (July-December 1999) in comparison to the period 1992 to March 24, 1999, and after the bombing of targets in Serbia (2000-2002). Maintaining the character of occurrence of LEC in BAL as nonspecific (Zunic et al. 1996), the devastating power of alpha particles (originated from uranium decay) gives an opportunity to discuss this phenomenon more comprehensibly and perceive a new vista related to the pathogenesis of LEC phenomenon in BAL. Since the period after 1991 corresponds to the time after the first Gulf War, and later the bombing of targets in Bosnia, the possibility of occurrence of LEC in BAL as a manifestation of radiation alveolitis due to contamination by air transferred depleted uranium (DU) particles could not be excluded.
Assuntos
Partículas alfa/efeitos adversos , Líquido da Lavagem Broncoalveolar/citologia , Lúpus Eritematoso Sistêmico/etiologia , Síndrome do Golfo Pérsico/etiologia , Alvéolos Pulmonares/efeitos da radiação , Lesões por Radiação/complicações , Urânio/efeitos adversos , Criança , HumanosRESUMO
The study was based on theoretical interpretation of authentic findings of Lupus Erythematosus Cells (LEC) in bronchoalveolar lavage (BAL) samples of children who underwent flexible bronchoscopy for clinical symptoms and radiological changes consistent with persistent pulmonary infiltrates during the first year after the bombing of Serbia in 1999. Differential cell counts were compared and statistical significance of differences for estimated cell population percentages calculated in groups of LEC positive (LEC+) and LEC negative (LEC-) BAL specimens. Significant increase of percentages of neutrophils and eosinophils and decreased percentages of macrophages were found in the group of LEC+ in comparison with LEC- BAL specimens (p less than 0.05, p less than 0.001, p less than 0.001, respectively). Presence of decreased percentages of cells of monocyte-macrophage lineage with consequent expansion of white blood cells in BAL, argue for understanding the nature of LEC+ alveolitis as a possible nonspecific finding of radiation-induced biological response of pulmonary tissue. LEC phenomenon may be understood as an early radio adaptive tissue response. Depleted uranium (DU) radiotoxic effect with concomitant alpha particles radiation, has been associated with unpredictable and everlasting biological effects. The emission of radiation in the course of several decades due to corrosion of scattered remnants of DU armaments, which has been potentiated by the repeated bombing of the regions within range of the transfer of radioactive particles by air, strikes a broad territory and numerous populations, and unavoidably leads to in vivoPetkau effect. Except the war, peacetime nuclear disasters in various parts of the world, such as Fukushima, Chernobyl and others, contribute to this effect too. In this way, the Petkau effect is a challenge for science to declare the future health strategy with the main goal focused on minimizing the early, as well as delayed in vivo effects of depleted uranium.
Assuntos
Lúpus Eritematoso Sistêmico/etiologia , Alvéolos Pulmonares/efeitos da radiação , Lesões por Radiação/sangue , Poluentes Radioativos/efeitos adversos , Urânio/efeitos adversos , Partículas alfa/efeitos adversos , Líquido da Lavagem Broncoalveolar/citologia , Broncoscopia , Comunicação Celular , Criança , Humanos , Alvéolos Pulmonares/patologia , Lesões por Radiação/complicaçõesRESUMO
Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease where genetic susceptibility coupled with largely undefined environmental factors is reported to underlie the aetiology of the disease. One such factor is low vitamin D status. The primary source of vitamin D is endogenous synthesis following exposure of the skin to UVB light. Photosensitivity, sunlight avoidance and the use of sun protection factor in combination with medications prescribed to treat the symptoms of the disease, puts SLE patients at increased risk of vitamin D deficiency. Decreased conversion of 25-hydroxyvitamin D to the metabolically active form, 1,25-dihydroxyvitamin D3, is possible, due to renal impairment common in SLE putting additional stress on vitamin D metabolism. The majority of studies have identified low 25-hydroxyvitamin D in SLE patients, albeit using varying cut-offs (<25 to <80 nmol/l). Of these studies, fifteen have investigated a link between status and disease activity with conflicting results. Variation with disease activity index measures used alongside methodological limitations within the study design may partially explain these findings. This review discusses the importance of optimal vitamin D status in SLE, critically evaluates research carried out to date that has investigated vitamin D in SLE, and highlights the need for a well-designed observational study that controls for diet, medication use, dietary supplements, UV exposure and seasonality, that uses sensitive methods for measuring vitamin D status and disease activity in SLE to conclusively establish the role of vitamin D in SLE.
Assuntos
Lúpus Eritematoso Sistêmico/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Vitaminas/sangue , Nível de Saúde , Humanos , Nefropatias/sangue , Nefropatias/etiologia , Lúpus Eritematoso Sistêmico/sangue , Índice de Gravidade de Doença , Deficiência de Vitamina D/sangueRESUMO
The stem bark of Eucommia ulmoides Oliv. is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia in traditional Chinese medicine. This study was to determine whether the crude polysaccharides (EUPs) isolated from the stem bark of E. ulmoides had beneficial effects on lupus-like syndrome in mice. BALB/c mice were immunized with CJ-S(131) in Freund's complete adjuvant on day 0, and then boosted on day 14. EUPs 15 or 30 mg kg(-1)·day(-1), or prednisone 5 mg kg(-1)·day(-1) was given to BALB/c mice intragastrically from day 0 to 34. Treatment with EUPs 15 or 30 mg kg(-1)·day(-1) for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. These findings suggested that Eucommia polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndrome induced by CJ-S(131) in BALB/c mice.
Assuntos
Eucommiaceae , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Fitoterapia , Polissacarídeos/uso terapêutico , Animais , Autoanticorpos/sangue , Campylobacter jejuni/imunologia , Campylobacter jejuni/patogenicidade , Inativadores do Complemento/isolamento & purificação , Inativadores do Complemento/uso terapêutico , Modelos Animais de Doenças , Eucommiaceae/química , Feminino , Imunoglobulina G/sangue , Rim/imunologia , Rim/patologia , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/imunologia , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos BALB C , Casca de Planta/química , Polissacarídeos/isolamento & purificação , SíndromeRESUMO
Calcinosis cutis is a common clinical feature of dermatomyositis and scleroderma but rarely reported in association with systemic lupus erythematosus (SLE). Calcinosis cutis in SLE occurs without calcium and phosphorus metabolic abnormalities and may be localized or generalized. The pathophysiology remains unclear and no effective therapy is currently available. We report a 30-year-old woman with a 13-year history of SLE who developed multiple calcinosis cutis around both knees and we review the relevant published work.