RESUMEN
Hydroxyl-methyl-glutaryl-Co-A reductase (HMGCR) immune mediated necrotising myopathy (IMNM) is a rare autoimmune myositis that is thought to be triggered by statins and responds to immunomodulation. We report a case of a woman in her 30s with HMGCR IMNM without a history of statin exposure who had a clear flare of her myositis after beginning mushroom supplements. Mushrooms are natural HMGCR inhibitors, and this is the first case to demonstrate a flare triggered by mushrooms in a patient with known HMGCR IMNM. This case highlights the importance of reviewing diet and supplements in patients with IMNM. It also emphasises the importance of strict statin avoidance for patients with IMNM even when the myositis is under good control.
Asunto(s)
Agaricales , Enfermedades Autoinmunes , Suplementos Dietéticos , Enfermedades Musculares , Adulto , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Suplementos Dietéticos/efectos adversos , Femenino , Humanos , Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hidroximetilglutaril-CoA Reductasas/inmunología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Músculo Esquelético/inmunología , Músculo Esquelético/patología , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/inmunología , Enfermedades Musculares/patología , Miositis/inducido químicamente , Miositis/diagnóstico , Miositis/inmunología , Miositis/patología , Necrosis/inducido químicamente , Necrosis/inmunología , Fitoterapia/efectos adversos , Brote de los SíntomasAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Autoanticuerpos/sangre , Vértebras Cervicales/diagnóstico por imagen , Conectina/inmunología , Miositis/inducido químicamente , Anciano , Femenino , Humanos , Magnetoterapia , Miositis/sangre , Miositis/diagnóstico por imagen , Miositis/inmunologíaRESUMEN
The idiopathic inflammatory myopathies, particularly dermatomyositis, are associated with an increased risk of cancer. Lung, ovarian, breast, colon, prostate, and cervical cancers, and hematologic malignancies, are among the most common associated cancers. Risk stratification for cancer in patients with myositis is based on clinical risk factors/red flags, myositis clinical subtypes, and myositis-specific autoantibodies. Clinical risk factors include older age at disease onset, male gender, dysphagia, acute onset/refractory myositis, cutaneous ulceration, necrosis/vasculitis, and elevated inflammatory markers. Appropriate screening strategies are based on the risk level. Further studies are warranted to determine the role of advanced imaging and comprehensive cancer screening.
Asunto(s)
Detección Precoz del Cáncer/métodos , Miositis/complicaciones , Neoplasias/diagnóstico , Autoanticuerpos/inmunología , Humanos , Miositis/inmunología , Neoplasias/etiología , Neoplasias/inmunología , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVES: In autoimmunity, autoantibodies (aAb) may be simple biomarkers of disease or true pathogenic effectors. A form of idiopathic inflammatory myopathy associated with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) aAb has been individualised and is referred to as immune-mediated necrotising myopathy (IMNM). The level of aAb correlates with IMNM activity and disease may respond to immunosuppression, suggesting that they are pathogenic. We aimed to evaluate the pathogenicity of IgG from patients with anti-SRP or anti-HMGCR aAb in vivo by developing the first mouse model of IMNM. METHODS: IgG from patients suffering from anti-SRP or anti-HMGCR associated IMNM were passively transferred to wild-type, Rag2-/- or complement C3-/- mice. Muscle deficiency was evaluated by muscle strength on electrostimulation and grip test. Histological analyses were performed after haematoxylin/eosin staining or by immunofluorescence or immunohistochemistry analysis. Antibody levels were quantified by addressable laser bead assay (ALBIA). RESULTS: Passive transfer of IgG from patients suffering from IMNM to C57BL/6 or Rag2-/- mice provoked muscle deficiency. Pathogenicity of aAb was reduced in C3-/- mice while increased by supplementation with human complement. Breakage of tolerance by active immunisation with SRP or HMGCR provoked disease. CONCLUSION: This study demonstrates that patient-derived anti-SRP+ and anti-HMGCR+ IgG are pathogenic towards muscle in vivo through a complement-mediated mechanism, definitively establishing the autoimmune character of IMNM. These data support the use of plasma exchanges and argue for evaluating complement-targeting therapies in IMNM.
Asunto(s)
Autoanticuerpos/inmunología , Hidroximetilglutaril-CoA Reductasas/inmunología , Inmunoglobulina G/inmunología , Miositis/inmunología , Partícula de Reconocimiento de Señal/inmunología , Animales , Proteínas del Sistema Complemento/inmunología , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos C57BL , Fuerza Muscular/inmunología , Músculo Esquelético/inmunología , Necrosis/inmunologíaRESUMEN
We describe the successful management of Anncaliia algerae microsporidial myositis in a man with graft versus host disease after hemopoietic stem cell transplantation. We also summarize clinical presentation and management approaches and discuss the importance of research into the acquisition of this infection and strategies for prevention.
Asunto(s)
Albendazol/uso terapéutico , Antiprotozoarios/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Microsporidios/aislamiento & purificación , Miositis/tratamiento farmacológico , Esporas Fúngicas/aislamiento & purificación , Anciano , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Humanos , Inmunosupresores/uso terapéutico , Masculino , Microsporidios/efectos de los fármacos , Microsporidios/patogenicidad , Miositis/diagnóstico , Miositis/inmunología , Miositis/microbiología , Nueva Gales del Sur , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/patogenicidad , Trasplante HomólogoRESUMEN
A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system.
Asunto(s)
Antioxidantes/uso terapéutico , Ejercicio Físico , Estilo de Vida Saludable , Músculo Esquelético/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Daño por Reperfusión/prevención & control , Animales , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/metabolismo , Supervivencia Celular , Dieta Saludable , Suplementos Dietéticos , Humanos , Mitocondrias Musculares/enzimología , Mitocondrias Musculares/inmunología , Mitocondrias Musculares/metabolismo , Fatiga Muscular , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inmunología , Músculo Esquelético/fisiopatología , Mialgia/etiología , Mialgia/prevención & control , Miositis/inmunología , Miositis/prevención & control , Consumo de Oxígeno , Esfuerzo Físico , Especies de Nitrógeno Reactivo/antagonistas & inhibidores , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/inmunología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatologíaRESUMEN
Although muscle weakness is the pathognomonic feature of idiopathic inflammatory myopathies, systemic organ involvement is not uncommon. The gastrointestinal and hepatic manifestations are well known. Oropharyngeal dysphagia is the most common gastrointestinal symptom and can be severe. Gastric and small intestinal motility disorders, including chronic intestinal pseudo-obstruction, celiac disease, and inflammatory bowel disease have been described. Comprehensive cancer screening is warranted soon after the diagnosis of inflammatory myopathies due to high risk of occult malignancies. Elevated aminotransferases may suggest muscular injury rather than hepatic dysfunction. Knowledge regarding systemic involvement of inflammatory myopathies can assist in timely diagnosis of these complex disorders.
Asunto(s)
Enfermedades Gastrointestinales , Tracto Gastrointestinal , Hepatopatías , Miositis , Detección Precoz del Cáncer , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/inmunología , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/fisiopatología , Humanos , Hepatopatías/diagnóstico , Hepatopatías/etiología , Hepatopatías/inmunología , Miositis/complicaciones , Miositis/inmunología , Miositis/patología , Medición de RiesgoRESUMEN
RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.
Asunto(s)
Aminoacil-ARNt Sintetasas/inmunología , Autoanticuerpos/sangre , Dermatomiositis/complicaciones , Fibrosis Pulmonar Idiopática/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Miositis/inmunología , Adulto , Anciano , Autoanticuerpos/inmunología , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/mortalidad , Dermatomiositis/inmunología , Dermatomiositis/mortalidad , Femenino , Humanos , Oxigenoterapia Hiperbárica/métodos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Mortalidad , Miositis/mortalidad , Estudios Observacionales como Asunto , Evaluación de Resultado en la Atención de Salud , Pronóstico , ARN/inmunología , Estudios Retrospectivos , Análisis de Supervivencia , Capacidad Vital/fisiologíaRESUMEN
Exercise training intensity is the major variant that influences the relationship between exercise, redox balance, and immune response. Supplement intake is a common practice for oxidative stress prevention; the effects of vitamin A (VA) on exercise training are not yet described, even though this molecule exhibits antioxidant properties. We investigated the role of VA supplementation on redox and immune responses of adult Wistar rats subjected to swimming training. Animals were divided into four groups: sedentary, sedentary + VA, exercise training, and exercise training + VA. Over eight weeks, animals were submitted to intense swimming 5 times/week and a VA daily intake of 450 retinol equivalents/day. VA impaired the total serum antioxidant capacity acquired by exercise, with no change in interleukin-1ß and tumor necrosis factor-α levels. In skeletal muscle, VA caused lipid peroxidation and protein damage without differences in antioxidant enzyme activities; however, Western blot analysis showed that expression of superoxide dismutase-1 was downregulated, and upregulation of superoxide dismutase-2 induced by exercise was blunted by VA. Furthermore, VA supplementation decreased anti-inflammatory interleukin-10 and heat shock protein 70 expression, important factors for positive exercise adaptations and tissue damage prevention. Our data showed that VA supplementation did not confer any antioxidative and/or protective effects, attenuating exercise-acquired benefits in the skeletal muscle.
Asunto(s)
Suplementos Dietéticos/efectos adversos , Proteínas HSP70 de Choque Térmico/antagonistas & inhibidores , Interleucina-10/antagonistas & inhibidores , Músculo Esquelético/metabolismo , Miositis/etiología , Estrés Oxidativo , Vitamina A/efectos adversos , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Western Blotting , Proteínas HSP70 de Choque Térmico/metabolismo , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Interleucina-10/metabolismo , Peroxidación de Lípido , Masculino , Músculo Esquelético/enzimología , Músculo Esquelético/inmunología , Miositis/sangre , Miositis/inmunología , Miositis/metabolismo , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/química , Oxidorreductasas/metabolismo , Capacidad de Absorbancia de Radicales de Oxígeno , Condicionamiento Físico Animal/efectos adversos , Distribución Aleatoria , Ratas WistarRESUMEN
BACKGROUND: Exercise under hypoxic conditions represents an additional stress in relation to exercise in normoxia. Hypoxia induces oxidative stress and inflammation as mediated through tumour necrosis factor (TNF)-α release that might be exacerbated through exercise. In addition, vitamin E supplementation might attenuate oxidative stress and inflammation resulting from hypoxia during exercise. The present study aimed to evaluate the effects of vitamin E supplementation (250 mg) on inflammatory parameters and cellular damage after exercise under hypoxia simulating an altitude of 4200 m. METHODS: Nine volunteers performed three sessions of 60 min of exercise (70% maximal oxygen uptake) interspersed for 1 week under normoxia, hypoxia and hypoxia after vitamin E supplementation 1 h before exercise. Blood was collected before, immediately after and at 1 h after exercise to measure inflammatory parameters and cell damage. RESULTS: Percentage oxygen saturation of haemoglobin decreased after exercise and recovered 1 h later in the hypoxia + vitamin condition (P < 0.05). Supplementation decreased creatine kinase (CK)-TOTAL, CK-MB and lactate dehydrogenase 1 h after exercise (P < 0.05). The exercise in hypoxia increased interleukin (IL)-6, TNF-α, IL-1ra and IL-10 immediately after exercise (P < 0.05). Supplementation reversed the changes observed after exercise in hypoxia without supplementation (P < 0.05). CONCLUSIONS: We conclude that 250 mg of vitamin E supplementation at 1 h before exercise reduces cell damage markers after exercise in hypoxia and changes the concentration of cytokines, suggesting a possible protective effect against inflammation induced by hypoxia during exercise.
Asunto(s)
Mal de Altura/fisiopatología , Antioxidantes/uso terapéutico , Suplementos Dietéticos , Ejercicio Físico , Miositis/prevención & control , Estrés Oxidativo , Vitamina E/uso terapéutico , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Cámaras de Exposición Atmosférica , Biomarcadores/sangre , Método Doble Ciego , Humanos , Masculino , Músculo Esquelético/inmunología , Músculo Esquelético/fisiopatología , Miositis/etiología , Miositis/inmunología , Consumo de Oxígeno , Carrera , Fenómenos Fisiológicos en la Nutrición Deportiva , Factores de Tiempo , Adulto JovenRESUMEN
There have been many cases of the appearance of autoantibodies and symptoms of disease after exposure to adjuvants, not only after breast augmentation with silicone implants, but also as a very rare vaccination side effect, such as Gulf war syndrome or macrophagic myofasciitis syndrome. Diseases whose symptoms developed after such adjuvant exposure are called autoimmune/ inôlammatory syndrome induced by adjuvants (ASIA). The group of adjuvants includes not only silicone implants, silica, squalen and aluminium, but also ink components used for making tattoos. Analyzing the available reports on the inôluence of adjuvants on the development of autoimmune diseases, the conclusion is that apart from long -term silicone exposure, the coexistence of other factors such as genetic or environmental is also necessary. Metaanalyses clearly do not conôirm an increased risk of developing autoimmune disease after breast augmentation with silicone implants, or tattooing, but it seems that among these patients there is a group that is more predestined to develop disease symptoms. In the general population the beneôits of vaccination are obvious, and the risk of severe adverse events following immunisation is incomparably lower than the risk of developing a speciôic disease and its complications, also for patients with diagnosed autoimmune diseases. Because of data heterogeneity in previous studies and difôiculties in diagnosing ASIA it seems necessary to conduct further analyses of adjuvants' inôluence on autoimmune disease development, and to reôine ASIA diagnostic criteria, which now allow too easy a diagnosis of this syndrome.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , Implantes de Mama/efectos adversos , Fascitis/inducido químicamente , Fascitis/inmunología , Humanos , Miositis/inducido químicamente , Miositis/inmunología , Síndrome del Golfo Pérsico/inducido químicamente , Síndrome del Golfo Pérsico/inmunología , Tatuaje/efectos adversos , Vacunación/efectos adversosRESUMEN
Skeletal muscle plays a major role in the control of whole body glucose disposal in response to insulin stimulus. Excessive supply of fatty acids to this tissue triggers cellular and molecular disturbances leading to lipotoxicity, inflammation, mitochondrial dysfunctions, impaired insulin response and decreased glucose uptake. This study was conducted to analyze the preventive effect of docosahexaenoic acid (DHA), a long-chain polyunsaturated n-3 fatty acid, against insulin resistance, lipotoxicity and inflammation in skeletal muscle at doses compatible with nutritional supplementation. DHA (30 µM) prevented insulin resistance in C2C12 myotubes exposed to palmitate (500 µM) by decreasing protein kinase C (PKC)-θ activation and restoring cellular acylcarnitine profile, insulin-dependent AKT phosphorylation and glucose uptake. Furthermore, DHA protected C2C12 myotubes from palmitate- or lipopolysaccharide-induced increase in Ptgs2, interleukin 6 and tumor necrosis factor-α mRNA level, probably through the inhibition of p38 MAP kinase and c-Jun amino-terminal kinase. In LDLR -/- mice fed a high-cholesterol-high-sucrose diet, supplementation with DHA reaching up to 2% of daily energy intake enhanced the insulin-dependent AKT phosphorylation and reduced the PKC-θ activation in skeletal muscle. Therefore, DHA used at physiological doses participates in the regulation of muscle lipid and glucose metabolisms by preventing lipotoxicity and inflammation.
Asunto(s)
Suplementos Dietéticos , Ácidos Docosahexaenoicos/uso terapéutico , Aceites de Pescado/uso terapéutico , Resistencia a la Insulina , Metabolismo de los Lípidos , Músculo Esquelético/metabolismo , Miositis/prevención & control , Absorción Fisiológica , Animales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/prevención & control , Dieta Occidental/efectos adversos , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/metabolismo , Aceites de Pescado/administración & dosificación , Glucosa/metabolismo , Miembro Posterior , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Ratones , Ratones Noqueados , Músculo Esquelético/enzimología , Músculo Esquelético/inmunología , Miositis/sangre , Miositis/inmunología , Miositis/metabolismo , Fosforilación , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Proteína Quinasa C-theta , Procesamiento Proteico-Postraduccional , Proteínas Proto-Oncogénicas c-akt/agonistas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , AtúnRESUMEN
Idiopathic inflammatory myopathies are systemic, immune-mediated diseases characterized by proximal, symmetrical, progressive muscle weakness. The aim of this work is to give an overview of the biological therapy used in the treatment of idiopathic inflammatory myopathies. The authors also focus on novel results in the therapy directed against the B- and T-cells. They emphasize the importance of new trials in these diseases which may lead to the introduction of novel therapeutic options in these disorders.
Asunto(s)
Terapia Biológica , Miositis/tratamiento farmacológico , Miositis/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales de Origen Murino/farmacología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Terapia Biológica/métodos , Ensayos Clínicos como Asunto , Proteínas del Sistema Complemento/efectos de los fármacos , Proteínas del Sistema Complemento/inmunología , Humanos , Inmunidad Celular/efectos de los fármacos , Factores Inmunológicos/farmacología , Activación de Linfocitos/efectos de los fármacos , Debilidad Muscular/etiología , Miositis/complicaciones , Miositis/terapia , Rituximab , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Inflamación/diagnóstico , Inflamación/inmunología , Aluminio/efectos adversos , Autoanticuerpos/biosíntesis , Fascitis/inmunología , Humanos , Miositis/inmunología , Síndrome del Golfo Pérsico/inmunología , Síndrome del Edificio Enfermo/inmunología , Siliconas/efectos adversos , Silicosis/inmunología , Síndrome , Terpenos/efectos adversos , Vacunas/inmunologíaRESUMEN
OBJECTIVES: To assess the efficacy and safety of B-lymphocyte depletion therapy (BCDT) utilising rituximab in refractory idiopathic inflammatory myositis. METHODS: We retrospectively evaluated 16 adult patients with active dermatomyositis (DM) or polymyositis (PM) who received 1 gram rituximab intravenous infusions two weeks apart after failing to respond to conventional therapy. The clinical and biochemical response were analysed by the Myositis Intention to Treat index (MITAX) and the serum creatine kinase (CK) levels at baseline and 6 and 12 months after treatment. The primary efficacy outcome was 20% improvement in the MITAX index and 30% reduction in CK. RESULTS: Eight patients responded to treatment and achieved both the MITAX and CK levels objectives within 6 months of rituximab therapy. Five out of these 8 responders remained clinically stable at 12 months and CK levels were still reduced or normalised. Of note, 4 patients who did not respond were re-assessed and had their diagnoses corrected. All patients showed adequate B cell depletion (BCD) with re-population occurring for a 15.4 months average (range 3-42 months). Those simultaneously treated with cyclophosphamide achieved more long-lasting depletion (average 18.6 months). CONCLUSIONS: The heterogeneous clinical and serological characteristics of patients diagnosed with IIM probably explain why some, but not all patients respond to rituximab. Myositis overlap and anti-synthetase syndromes seem to respond better than other patient subsets.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Factores Inmunológicos/uso terapéutico , Miositis/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Biomarcadores/sangre , Creatina Quinasa/sangre , Esquema de Medicación , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Miositis/sangre , Miositis/diagnóstico , Miositis/inmunología , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Factores de Tiempo , Resultado del TratamientoRESUMEN
An adjuvant is a substance that enhances the antigen-specific immune response, induces the release of inflammatory cytokines, and interacts with Toll-like receptors and the NALP3 inflammasome. The immunological consequence of these actions is to stimulate the innate and adaptive immune response. The activation of the immune system by adjuvants, a desirable effect, could trigger manifestations of autoimmunity or autoimmune disease. Recently, a new syndrome was introduced, autoimmune/inflammatory syndrome induced by adjuvants (ASIA), that includes postvaccination phenomena, macrophagic myofasciitis, Gulf War syndrome and siliconosis. This syndrome is characterized by nonspecific and specific manifestations of autoimmune disease. The main substances associated with ASIA are squalene (Gulf War syndrome), aluminum hydroxide (postvaccination phenomena, macrophagic myofasciitis) and silicone with siliconosis. Mineral oil, guaiacol and iodine gadital are also associated with ASIA. The following review describes the wide clinical spectrum and pathogenesis of ASIA including defined autoimmune diseases and nonspecific autoimmune manifestations, as well as the outlook of future research in this field.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Enfermedades Autoinmunes/inmunología , Fascitis/inmunología , Inflamación/inmunología , Miositis/inmunología , Síndrome del Golfo Pérsico/inmunología , Silicosis/inmunología , Inmunidad Adaptativa , Adyuvantes Inmunológicos/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/efectos adversos , Animales , Enfermedades Autoinmunes/inducido químicamente , Fascitis/inducido químicamente , Humanos , Inmunidad Innata , Inflamasomas/metabolismo , Inflamación/inducido químicamente , Miositis/inducido químicamente , Síndrome del Golfo Pérsico/inducido químicamente , Siliconas/administración & dosificación , Siliconas/efectos adversos , Escualeno/administración & dosificación , Escualeno/efectos adversos , Síndrome , Receptores Toll-Like/metabolismoAsunto(s)
Enfermedades Autoinmunes/etiología , Inflamación/etiología , Miositis/etiología , Fibrosis Pulmonar/etiología , Adyuvantes Inmunológicos/efectos adversos , Enfermedades Autoinmunes/inmunología , Implantes de Mama/efectos adversos , Femenino , Humanos , Inflamación/inmunología , Persona de Mediana Edad , Miositis/inmunología , Falla de Prótesis , Fibrosis Pulmonar/inmunología , Rotura , Geles de Silicona/efectos adversos , SíndromeRESUMEN
Recently, reports have suggested grouping different autoimmune conditions that are triggered by external stimuli as a single syndrome called autoimmune syndrome induced by adjuvants (ASIA). This syndrome is characterized by the appearance of myalgia, myositis, muscle weakness, arthralgia, arthritis, chronic fatigue, sleep disturbances, cognitive impairment and memory loss, and the possible emergence of a demyelinating autoimmune disease caused by systemic exposure after vaccines and adjuvants. As there are no markers for ASIA, the authors intend to present ASIA, or Shoenfeld's syndrome, as an autoimmune syndrome induced by adjuvants.
Asunto(s)
Adyuvantes Farmacéuticos/efectos adversos , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/inmunología , Cadenas HLA-DRB1/inmunología , Vacunas/efectos adversos , Artralgia/inmunología , Artritis/inmunología , Enfermedades Autoinmunes/epidemiología , Biomarcadores/metabolismo , Trastornos del Conocimiento/inmunología , Fatiga/inmunología , Humanos , Inflamación/inmunología , Trastornos de la Memoria/inmunología , Debilidad Muscular/inmunología , Mialgia/inmunología , Miositis/inmunología , Rumanía/epidemiología , Siliconas/efectos adversos , Trastornos del Sueño-Vigilia/inmunología , SíndromeRESUMEN
Blueberries are rich in antioxidants known as anthocyanins, which may exhibit significant health benefits. Strenous exercise is known to acutely generate oxidative stress and an inflammatory state, and serves as an on-demand model to test antioxidant and anti-inflammatory compounds. The purpose of this study was to examine whether 250 g of blueberries per day for 6 weeks and 375 g given 1 h prior to 2.5 h of running at â¼72% maximal oxygen consumption counters oxidative stress, inflammation, and immune changes. Twenty-five well-trained subjects were recruited and randomized into blueberry (BB) (N = 13) or control (CON) (N = 12) groups. Blood, muscle, and urine samples were obtained pre-exercise and immediately postexercise, and blood and urine 1 h postexercise. Blood was examined for F2-isoprostanes for oxidative stress, cortisol, cytokines, homocysteine, leukocytes, T-cell function, natural killer (NK), and lymphocyte cell counts for inflammation and immune system activation, and ferric reducing ability of plasma for antioxidant capacity. Muscle biopsies were examined for glycogen and NFkB expression to evaluate stress and inflammation. Urine was tested for modification of DNA (8-OHDG) and RNA (5-OHMU) as markers of nucleic acid oxidation. A 2 (treatment) × 3 (time) repeated measures ANOVA was used for statistical analysis. Increases in F2-isoprostanes and 5-OHMU were significantly less in BB and plasma IL-10 and NK cell counts were significantly greater in BB vs. CON. Changes in all other markers did not differ. This study indicates that daily blueberry consumption for 6 weeks increases NK cell counts, and acute ingestion reduces oxidative stress and increases anti-inflammatory cytokines.
Asunto(s)
Antioxidantes/uso terapéutico , Arándanos Azules (Planta) , Ejercicio Físico , Frutas , Células Asesinas Naturales/inmunología , Miositis/prevención & control , Estrés Oxidativo , Adolescente , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/análisis , Atletas , Biomarcadores/sangre , Biomarcadores/orina , Arándanos Azules (Planta)/química , F2-Isoprostanos/sangre , Frutas/química , Humanos , Interleucina-10/sangre , Recuento de Linfocitos , Miositis/sangre , Miositis/inmunología , Miositis/orina , Resistencia Física , Carrera , Timidina/análogos & derivados , Timidina/orina , Adulto JovenRESUMEN
Recently, Shoenfeld and Agmon-Levin described a potential new syndrome, namely ASIA - autoimmune/inflammatory syndrome induced by adjuvants, that comprises four medical conditions: siliconosis, the Gulf war syndrome, the macrophagic myofasciitis syndrome and post-vaccination phenomena, characterized by hyperactive immune responses accompanied by a similar complex of signs and symptoms. Most relevantly, these conditions share a linkage represented by adjuvants. This common soil may possibly induce autoimmune or auto-inflammatory diseases in humans as it was demonstrated in different animal models. Reconsidering under a unified umbrella this apparently detached condition is not only intriguing, but also provocative, and may help in unraveling novel pathogenetic mechanisms, preventive measures, and therapeutic targets.