Atualização na etiopatogênese da esclerose sistêmica

Abstract

Systemic Sclerosis (SSc) is an autoimmune disease of multifactorial etiology, triggered by a combination of genetic and environmental factors. Its varied clinical expression results from the complex physiopathogenic interaction of three main elements: proliferative vasculopathy, immune dysregulation and abnormal deposition and remodeling of the extracellular matrix (ECM), of which the characteristic disease fibrosis is the result. Early physiopathogenic events appear to be endothelial injury and imbalance in vascular repair with the activation of endothelial cells, the immune system and platelets, with the release of multiple mediators such as TH2 proinflammatory cytokines and growth factors, triggering a sequence of simultaneous or cascading events that involve several intracellular signaling pathways. The most important result of these events is the hyperactivation of fibroblasts, the main effector cells of fibrosis, which will then produce large amounts of ECM constituents and secrete multiple growth factors and cytokines that perpetuate the process. In this article we review the main factors potentially involved in the etiology of SSc and reexamine the current knowledge about the most important mechanisms involved in the development of lesions that are characteristic of the disease. A better understanding of these physiopathogenic mechanisms will help identify potential therapeutic targets, which may result in advances in the management of this complex and debilitating disease.

Alterações retrococleares na esclerose sistêmica: relato de casos

“…In the calculation of normality patterns, a standard deviation of ±2.5 errors was considered for each variable in order to obtain a 95% confidence interval (13) . The electrodes were placed according to the following pattern: the negative electrode at the vertex, the earth electrode on the side of the forehead, and the negative electrodes in the regions of the left and right mastoid muscles (9,13) . Initial acoustic stimulus intensity of 80 dB nNA was used, but it was increased in 10 dB nNA when needed, as to adapt to patients with hearing loss (9) .…”

“…The electrodes were placed according to the following pattern: the negative electrode at the vertex, the earth electrode on the side of the forehead, and the negative electrodes in the regions of the left and right mastoid muscles (9,13) . Initial acoustic stimulus intensity of 80 dB nNA was used, but it was increased in 10 dB nNA when needed, as to adapt to patients with hearing loss (9) . Regarding the other parameters of the examination, the manufacturer's suggestions were followed: rarefied polarity; acoustic stimulus generated through clicks; presentation rate of 17.1 stimuli per sec; low-pass filters of 5000 Hz and high-pass filters of 1000 Hz, bilaterally.…”

“…This mechanism of hypoxia in SSc is associated with activation of the endothelial cells by unknown factors, which promotes chronic endothelial injury with platelet adhesion and activation of the fibrinolytic system, thus generating increased vascular permeability and leukocyte adhesion to blood vessel wall. This process generates fibrosis and loss of elasticity, reducing the vascular lumen and causing progressive hypoxia and necrosis of the cochlear tissue (9) . Studies conducted to identify changes in the auditory system in SSc patients show that prevalence of auditory loss in these individuals varies considerably, but sensorineural hearing loss is the most frequently observed in these investigations.…”

Acute Respiratory Events in Connective Tissue Disorders

“…Of all CTDs, SLE presents a unique paradigm of disrupted immunity per se increasing the risk of infections attributable to the so-called lupus paradox, that is, a state of severely impaired cellular and humoral immune responses in spite of B-lymphocyte hyperactivity and high levels of γ-globulins, including high antibody titers against viruses and other pathogens and a high ability to attack ‘self-tissues' [26,54,57,58,59]. Recent data support an ‘intrinsic' defective response to infectious agents also in RA and scleroderma [60,61]. Bronchiectasis is known to result from and to perpetuate a ‘vicious cycle' of chronic bacterial infection and dysregulated inflammation and is therefore considered a ‘high-infection-risk' condition in RA patients (fig.…”

Autoanticorpos em esclerose sistêmica e sua correlação com as manifestações clínicas da doença em pacientes do Centro-Oeste do Brasil

“…7 Artigo de revisão de Zimmermann e Pizzichini destaca que os autoanticorpos específicos representam uma das marcas registradas da doença e se constituem na expressão mais evidente do envolvimento do sistema imune humoral na etiopatogênese da ES. 8 Esses autoanticorpos apresentam características fundamentais de uma resposta desencadeada por antígeno e são representados principalmente por: anticorpos anticentrômeros (ACA), anticorpos anti-DNA topoisomerase I (anti-SCL70) e anticorpos anti RNA polimerase III (anti-POL3). [9][10][11][12] Recentes estudos ressaltam o potencial patogênico de autoanticorpos em pacientes com ES e sugerem que anticorpos específicos contra fibroblastos, células endoteliais e receptores para o fator de crescimento derivado de plaquetas (PDGF) podem diretamente causar ativação de fibroblastos e células endoteliais e contribuir para o dano tecidual.…”