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Mechanical ventilation is an advanced life support treatment for patients with acute respiratory failure. While stabilizing respiratory function, it also acts as an injury factor to exacerbate or lead to lung injury, that is, ventilation-induced lung injury (VILI). There may be a more subtle form of damage to VILI known as "biotrauma". However, the mechanism of biotrauma in VILI is still unclear. This article intends to review the mechanism of biotrauma of VILI from the aspects of inflammatory response, oxidative stress and complement activation, in order to provide a new strategy for clinical prevention and treatment of biotrauma caused by VILI.
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Introducción: El eculizumab es un anticuerpo monoclonal de tipo IgG diseñado para el tratamiento de la hemoglobinuria paroxística nocturna (HPN), en el que su diana farmacológica forma parte del sistema del complemento. Su mecanismo de acción ha permitido implementarlo en el tratamiento de enfermedades huérfanas, como el síndrome urémico hemolítico atípico (SUHa), trastorno del espectro de la neuromielitis óptica (TENMO) y miastenia gravis, cuya incidencia, es baja. Asimismo, es viable en el tratamiento de Guillain Barré y el síndrome antifosfolípido catastrófico (CAPS). Objetivo: Evidenciar aplicaciones terapéuticas del eculizumab y beneficios más significativos en algunos padecimientos. Materiales y métodos: Se realizó búsqueda bibliográfica en el periodo 2010-2021, en bases de datos: Google Scholar, Science Direct, PubMed y Scielo, utilizando como palabra clave "eculizumab". Posteriormente, se afinó la búsqueda utilizando palabras claves asociadas a enfermedades tratadas con este medicamento. Resultados: Se identificó el mecanismo de acción del fármaco y su efecto sobre la patogénesis de hemoglobinuria paroxística nocturna, síndrome urémico atípico, miastenia gravis generalizada refractaria, trastorno del espectro de la neuromielitis óptica, síndromes antifosfolípidos catastrófico y Guillain-Barré. Conclusiones: El eculizumab tiene una alta seguridad y capacidad para tratar y disminuir síntomas de diversas enfermedades que involucran el sistema del complemento.
Introduction: Eculizumab is an IgG type monoclonal antibody designed to treat paroxysmal nocturnal hemoglobinuria (PNH) and its pharmacological target is a member of the complement system. Its mechanism of action has permitted its use in the treatment of orphan diseases such as atypical hemolytic uremic syndrome (aHUS), neuromyelitis optic spectrum disorder (NMOSD), and myasthenia gravis, all of which have a low incidence. Likewise, eculizumab is a viable treatment for Guillain Barré and catastrophic antiphospholipid syndrome (CAS). Objective: To describe the therapeutic applications of eculizumab and its most significant benefits in some illnesses. Materials and methods: A bibliographic search was carried out during the 2010-2021 period in Google Scholar, Science Direct, PubMed and Scielo databases using the keyword eculizumab. Then, the search was refined by using keywords associated with diseases treated with this medication. Results: The mechanism of action of the antibody and its effect on the pathogenesis of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, refractory generalized myasthenia gravis, neuromyelitis optic spectrum disorder, catastrophic antiphospholipid syndrome, and Guillain Barré were identified. Conclusions: Eculizumab has high safety and capacity in treating and diminishing symptoms of diverse illnesses, which involve the complement system.
Subject(s)
Humans , Antibodies, Monoclonal , Immunoglobulins , Hemoglobinuria, ParoxysmalABSTRACT
Objective:To investigate the role of complement activation in the pathogenesis of primary malignant hypertension (MHT) with nephrosclerosis complicated with severe cardiorenal injury.Methods:Data of MHT patients with nephrosclerosis proven by biopsy from January 2010 to December 2020 in the Beijing Anzhen Hospital, Capital Medical University were retrospectively analyzed. The expressions of complement-related component C4d, C1q, complement factor H-related protein 5, C3c and C5b-9 were detected by immunohistochemical staining. According to whether the patients were complicated with acute heart failure (AHF) and/or acute kidney injury (AKI), they were divided into severe cardiorenal injury group and non-severe cardiorenal injury group. The differences of clinicopathological data between the two groups were compared. According to the degree of C4d deposition in renal tissues, patients were divided into C4d diffused deposition group and non-C4d diffused deposition group. The severity of cardiorenal injury and the pathological characteristics of thrombotic microangiopathy in renal tissues were compared between the two groups.Results:A total of 33 patients were enrolled in this study, of which 17 cases (51.5%) were complicated with severe cardiorenal injury; AHF occurred in 16 patients (48.5%), AKI occurred in 8 patients (26.7%), and AHF and AKI were combined in 7 patients (21.2%). Compared with non-severe cardiorenal injury group, patients in severe cardiorenal injury group had higher levels of baseline lactate dehydrogenase [326.0 (217.0, 366.0) IU/L vs 197.0 (165.0, 220.0) IU/L, Z=37.000, P=0.002] and hemoglobin [(143.6±24.0) g/L vs (106.4±24.7) g/L, t=38.500, P<0.001], lower levels of 12 h urinary incontinence osmolality [400.0 (342.5, 504.0) mmol/L vs 476.0 (432.3, 616.5) mmol/L, Z=72.000, P=0.021] and serum albumin [(36.2±9.4) g/L vs (43.2±6.2) g/L, t=6.423, P=0.017], and thicker left ventricular posterior wall [(14.0±2.1) mm vs (12.1±1.1) mm, t=6.552, P=0.018]. The immunohistochemical results of kidney tissue showed that the proportions of C4d and C5b-9 diffused deposition in severe cardiorenal injury group were significantly higher than those in non-severe cardiorenal injury group (5/16 vs 0/15, P=0.043; 12/16 vs 5/15, P=0.032). Compared with non-C4d diffused deposition group, C4d diffused deposition group had higher incidence of AHF (5/5 vs 10/26, P=0.018), poorer heart function, more severe ventricular remodeling, and shorter history of hypertension [2.0 (0, 12.0) months vs 48.0 (9.5, 84.0) months, Z=22.500, P=0.022]. Conclusions:The incidence of severe cardiorenal injury in MHT patients with nephrosclerosis is about 51.5%. The proportion of diffuse deposition of complement activated components in renal tissues in patients with severe cardiorenal injury is higher than that in patients with non-severe cardiorenal injury. Overactivation of complement may be involved in the pathogenic process of severe heart and kidney injury caused by MHT.
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Trauma can trigger systemic pathological states, including coagulation disorders, tissue damage and metabolic disturbances, in which immune responses are extensively involved and play an important role. As an important component of innate immunity, the complement system is known to be implicated in the bactericidal process of lysis in vivo and can also induce immune inflammation in the body, but its role in trauma is not clear. The authors summarize the interaction between complement system activation and immune system, and the clinical translation of complement system intervention after trauma from the aspects of posttraumatic innate immunity, acquired immunity as well as there internal bridging, in order to provide more ideas for clinical trauma treatment.
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ABSTRACT Chagas disease (CD) is a chronic tropical disease caused by Trypanosoma cruzi , affecting about 8 million people in Latin America. The lectin pathway (LP) of the complement system is one of the first lines of host defense in the response against T. cruzi , and can continue to be activated in chronic infection due to the escape of the parasite to its action. Although some components of this pathway have been investigated in CD, there are no reports on its activation in patient serum. In this context, our objective was to evaluate the activation of LP in chronic chagasic patients and controls by the detection of the C4 component, using the direct ELISA assay. For this purpose, serum of 80 patient with chronic CD (clinical forms: asymptomatic n=17; symptomatic n=63; cardiac n=45; cardio digestive n=13; digestive n=5) followed at the Ambulatory of Attention to Chagasic Patients (HC/UFPR) and 80 healthy controls (donors of the Blood Bank of HC) were evaluated regarding the evaluation of the LP. The results showed that LP activation by mannose-binding lectin (MBL) was found reduced while activation by ficolins was increased in patients with CD when compared to controls. The same results were observed when the patients were categorized according to the indeterminate and symptomatic clinical forms. We conclude that the detection of the C4 component by ELISA is an efficient methodology to assess LP activation in serum from patients with chronic CD, enabling to differentiate the activation profile between patients and controls..
RESUMO A doença de Chagas (DC) é uma doença tropical crônica causada pelo Trypanosoma cruzi, atingindo cerca de 8 milhões de pessoas na América Latina. A via das lectinas (VL) do sistema complemento é uma das primeiras linhas de defesa na resposta imunológica contra a infecção pelo T. cruzi, e pode continuar sendo ativada na infecção crônicadevido ao escape do parasito à sua ação. Embora alguns componentes dessa via tenham sido investigados na DC, não existem relatos sobre sua ativação em soro de pacientes. Neste contexto, nosso objetivo foi avaliar a ativação da VL no soro de pacientes com DC crônica e controles pela detecção do componente C4 empregando a técnica de ELISA. Para isso, amostras de soro de 80 pacientes com DC crônica (formas clínicas: indeterminada n=17; sintomática n=63; cardíaca n=45; cardiodigestiva n=13; digestiva n=5) atendidos no Ambulatório de Atenção ao Paciente Chagásico (HC/UFPR) e 80 controles saudáveis (doadores do Banco de Sangue do HC) foram avaliados quanto a ativação da VL. Os resultados demonstraram que a ativação da VL pela lectina ligante de manose (MBL) encontra-se reduzida, enquanto que a ativação pelas ficolinas está aumentada em pacientes com DC quando comparados aos controles. Os mesmos resultados foram observados quando os pacientes foram categorizados quanto às formas clínicas indeterminada e sintomática. Concluímos que a detecção do componente C4 por ELISA é uma metodologia eficiente para avaliar a ativação da VL em soro de pacientes com DC crônica possibilitando diferenciar o perfil de ativação entre pacientes e controles.
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【Objective】 To construct an in-vitro model of erythrocyte antibody-mediated complement activation, and establish quantitative detection methods based on flow cytometry and spectrophotometry, so as to explore the correlation of anti-body titers and complement activation speed, and provide a methodological basis for studying the adverse transfusion reactions of anti-body mediated complement hemolysis. 【Methods】 Mouse monoclonal antibody that recognized human C3b and fluorescent secondary antibody were used to label C3b fragments on erythrocytes, and the deposition of C3b fragments after complement activation was detected by flow cytometry. The absorbance at 540 nm of the supernatant in the complement activation reaction system was measured by spectrophotometry as the amount of hemoglobin released was related to the absorbance. 【Results】 The complement activation system was constructed according to the ratio of 3% red blood cell suspension (mixed for 6 people) 1∶anti-Tja 1∶complement 2. The repeatability was good (P value>0.05) as different red blood cell mixtures had been used to repeat the detection reaction system. When using 32×, 64× and 128× dilutions of anti-Tja mediated complement activation, the deposition of C3b fragments has been detected by flow cytometry at 30 s, 1 min and 2 min, respectively, and MFI peaked at 5 min, 10 min and 30 min, respectively. No obvious hemolysis has been observed within 1.5 h. 【Conclusion】 In vitro model of anti-Tja-mediated complement activation demonstrates the speed of complement activation is related to the concentration of antibody. At a certain antibody concentration, the speed of complement activation has been slowed down, and no obvious hemolysis observed.
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Since the commercialization of the first liposomes used for drug delivery, Doxil/Caelyx® and Myocet®, tremendous progress has been made in understanding interactions between nanomedicines and biological systems. Fundamental work at the interface of engineering and medicine has allowed nanomedicines to deliver therapeutic small molecules and nucleic acids more efficiently. While nanomedicines are used in oncology for immunotherapy or to deliver combinations of cytotoxics, the clinical successes of gene silencing approaches like patisiran lipid complexes (Onpattro®) have paved the way for a variety of therapies beyond cancer. In parallel, the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the potential of mRNA vaccines to develop immunization strategies at unprecedented speed. To rationally design therapeutic and vaccines, chemists, materials scientists, and drug delivery experts need to better understand how nanotechnologies interact with the immune system. This review presents a comprehensive overview of the innate and adaptative immune systems and emphasizes the intricate mechanisms through which nanomedicines interact with these biological functions.
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Resumen La glomerulonefritis membranoproliferativa es una lesión poco frecuente que abarca un grupo de patologías que comparten un patrón histológico en común y pueden originarse a partir de diversos mecanismos patogénicos. Mediante biopsias renales se ha establecido que en estas lesiones el daño renal inicial ocurre por el depósito de inmunoglobulinas que generan depósitos subendoteliales, subepiteliales y/o en la membrana basal glomerular, con lo cual el glomérulo adopta frecuentemente un aspecto lobulado. Se presenta el caso de un hombre de 48 años, quien ingresó al servicio de urgencias del Hospital de San José de Bogotá, Colombia, sin antecedentes relevantes y presentó proteinuria en rango nefrótico severo (62 gramos en 24 horas), elevación de nitrogenados y reporte de biopsia con glomerulonefritis membranoproliferativa. Se describe el enfoque clínico y diagnóstico de esta entidad.
Abstract The membranophroliferative glomerulonephritis is a rare lesion that covers a group of pathologies that share a histologic pattern, and can generate from diverse pathogenic mechanisms. Based on the findings of the kidney biopsy, starts a process to search the etiology of the lesion. The initial kidney damage occurs due to the deposit of immunoglobulins, complement elements or both in the mesangium and in the capillary endothelium, generating sub endothelial, sub epithelial, and/or glomerular basal membrane deposits, frequently adopting glomerulus a lobed aspect. We present a case of a man 48 years old admitted in the emergency of the San Jose Hospital in Bogotá, without relevant pathological background that debuts with proteinuria in severe nephrotic range (62 grams in 24 hours), nitrogenous elevation and biopsy report with membranophroliferative glomerulonephritis, we describe de clinical and diagnostic approach of this entity.
Subject(s)
Humans , Male , Middle Aged , Glomerulonephritis, Membranoproliferative , Case Reports , Colombia , Diagnosis , Acute Kidney InjuryABSTRACT
@#Age-related macular degeneration is a macular disease which incidence increases with age. Currently, it is believed that its pathogenic factors are related to patients' age, heredity, smoking, oxidative stress, immune inflammatory response, RPE cell aging and metabolic abnormalities. Complement system plays an important role in the body's defense against infection, immune regulation and inflammatory response. Immune inflammation caused by abnormal activation of complement system is considered to be an important cause of ARMD in recent years. Autophagy also plays a role in ARMD. Normal autophagy is an important way for cells' self-protection and maintenance of homeostasis. When autophagy is blocked, oxidative stress can be aggravated, which will lead to the development of ARMD. The balance regulation between complement activation and autophagy is an important method to control the development of ARMD.
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El trasplante renal constituye la mejor opción de tratamiento para los pacientes con enfermedad renal crónica terminal. La supervivencia del injerto es de gran importancia y puede ser afectada por factores inmunológicos o no inmunológicos; esto unido al número de pacientes en las listas de espera, hace necesario definir estrategias de manejo que permitan tener mejores resultados a largo plazo. Objetivo. Determinar las características clínicas y humorales, y los desenlaces en receptores de trasplante renal o combinado hígado-riñón, altamente sensibilizados, que recibieron profilaxis combinada con inmunoglobulina intravenosa y plasmaféresis en el Hospital San Vicente Fundación, en Colombia. Materiales y métodos. Se realizó un estudio retrospectivo, observacional, descriptivo, que incluyó los pacientes trasplantados entre el 4 de julio de 2010 y el 19 de abril de 2017. Como variables se incluyeron, entre otras, la etiología de la enfermedad renal crónica, el tipo de terapia recibida, y el tiempo en lista de espera en días. Como desenlace se evaluó la presencia de rechazo, el tipo de rechazo, la pérdida del injerto, las complicaciones y la muerte. Resultados. Del total de 25 pacientes, el 100% recibió inmunoglobulina intravenosa y el 84% plasmaféresis. El 12% presentó rechazo del injerto, todos de tipo humoral, y el 20% perdió el injerto. Discusión. A pesar de la gran variedad de protocolos propuestos en la literatura, en esta población especial no se ha establecido un protocolo óptimo de inmunosupresión. El protocolo en nuestra pequeña cohorte no tuvo un impacto negativo en el porcentaje de infecciones postrasplante ni en la pérdida del injerto renal, pero sí redujo el tiempo en las listas de espera; por lo tanto, se requieren estudios adicionales para confirmar los hallazgos encontrados en este estudio
Kidney transplantation is the best treatment option for patients with terminal chronic kidney disease, regardless of the etiology, making graft survival an important feature, which may be affected by immunological or non-immunological factors. This, added to the increasing number of patients on waiting lists, makes it necessary to define management strategies for these patients that allow better long-term results. Objectives. To determine the clinical, humoral and outcome characteristics in highly sensitized recipients of kidney and simultaneous kidneyliver transplant who received combined prophylaxis with intravenous immunoglobulin and plasmapheresis therapy in a Colombian medical center. Materials and methods. A retrospective, observational, descriptive study was carried out that included the transplanted patients between July 4, 2010 and April 19, 2017. Variables included the etiology of chronic kidney disease, the type of therapy received, and waiting time in days, among others. As outcomes, the presence of rejection, type of rejection, graft loss, complications and death were evaluated. Results. From a total of 25 patients, 100% received intravenous immunoglobulin and 84% plasmapheresis. Twelve percent presented graft rejection, all humoral, and 20% lost the graft. Discussion. Despite the great variety of protocols proposed in the literature, an optimal immunosuppression protocol has not been established for this particular population. The protocol in our small cohort did not have a negative impact on the percentage of post-transplant infections nor in the loss of the renal graft, but it did reduce waiting time; therefore, additional studies are required to confirm the findings in this study
Subject(s)
Kidney Transplantation , Plasmapheresis , Complement Activation , Graft RejectionABSTRACT
@#Age-related macular degeneration is a macular disease which incidence increases with age. Currently, it is believed that its pathogenic factors are related to patients' age, heredity, smoking, oxidative stress, immune inflammatory response, RPE cell aging and metabolic abnormalities. Complement system plays an important role in the body's defense against infection, immune regulation and inflammatory response. Immune inflammation caused by abnormal activation of complement system is considered to be an important cause of ARMD in recent years. Autophagy also plays a role in ARMD. Normal autophagy is an important way for cells' self-protection and maintenance of homeostasis. When autophagy is blocked, oxidative stress can be aggravated, which will lead to the development of ARMD. The balance regulation between complement activation and autophagy is an important method to control the development of ARMD.
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Abstract Atypical hemolytic-uremic syndrome (aHUS) is a diagnosis of exclusion which should be proposed in cases where there is microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. It is associated with mutations which cause dysregulation of the complement system and implies an adverse prognosis and a high risk of progression to chronic kidney disease. Following, we present the case of a patient with aHUS, highlighting the effect and importance of biologic therapy with the monoclonal antibody eculizumab. (Acta Med Colomb 2019; 44. DOI:https://doi.org/10.36104/amc.2019.1301).
Resumen El síndrome hemolítico urémico atípico (SHUa) constituye un diagnóstico de exclusión que debe plantearse ante la presencia de anemia hemolítica microangiopática, trombocitopenia y lesión renal aguda. Está asociado con mutaciones que provocan una disregulación del sistema del complemento e implica un pronóstico adverso y alto riesgo de progresión a enfermedad renal crónica. A continuación, presentamos el caso de un paciente con SHUa resaltando el efecto e importancia de la terapia biológica con el anticuerpo monoclonal eculizumab. (Acta Med Colomb 2019; 44. DOI:https://doi.org/10.36104/amc.2019.1301).
Subject(s)
Male , Adult , Atypical Hemolytic Uremic Syndrome , Complement Activation , Thrombotic Microangiopathies , Kidney Failure, Chronic , Antibodies, MonoclonalABSTRACT
Abstract In kidney biopsies reviews, scleroderma renal crisis (SRC) is characterized by vascular endothelial injuries, C4d deposits on peritubular vessels, and acute and chronic injuries coexisting on the same biopsy. The clinical signs of thrombotic microangiopathy (TMA) are described in systemic sclerosis (SSc), nevertheless, it has not been related to acute injuries described on kidney biopsies. We report a case of SRC in a patient with scleroderma-dermatomyositis overlap syndrome, which also showed clinical and histopathological data of TMA. On fundus examination, a severe acute hypertensive retinopathy was found. The kidney biopsy showed severe endothelial damage with widening of mucoid cells at the level of the intima, focal concentric proliferation on most small arterioles, and C3, C4d, and IgM deposits along the capillary walls. The genetic study of complement only showed the presence of membrane cofactor protein (MCP) risk haplotypes, without other genetic complement disorders. We understand that in a patient with TMA and SSc, the kidney damage would be fundamentally endothelial and of an acute type; moreover, we would observe clear evidence of complement activation. Once further studies correlate clinical-analytical data with anatomopathological studies, it is likely that we will be forced to redefine the SRC concept, focusing on the relationship between acute endothelial damage and complement activation.
Resumo Nas revisões de biópsias renais, a crise renal esclerodérmica (CRE) é caracterizada por lesões endoteliais vasculares, depósitos de C4d em vasos peritubulares e lesões agudas e crônicas que coexistem na mesma biópsia. Os sinais clínicos de microangiopatia trombótica (MAT) são descritos na esclerose sistêmica (ES); no entanto, não foram relacionados às lesões agudas descritas nas biópsias renais. Relatamos um caso de CRE em um paciente com síndrome de superposição de esclerodermia-dermatomiosite, que também apresentou dados clínicos e histopatológicos de MAT. No exame de fundo do olho, foi encontrada uma retinopatia hipertensiva aguda grave. A biópsia renal mostrou lesão endotelial grave com alargamento das células mucoides ao nível da íntima, proliferação concêntrica focal na maioria das pequenas arteríolas e depósitos de C3, C4d e IgM ao longo das paredes dos capilares. O estudo genético do complemento mostrou apenas a presença de haplótipos de risco da proteína cofator de membrana (PCM), sem outros distúrbios genéticos do complemento. Entendemos que em um paciente com MAT e ES, o dano renal seria fundamentalmente endotelial e do tipo agudo; além disso, observaríamos evidências claras de ativação do complemento. Uma vez que novos estudos correlacionam dados clínico-analíticos com estudos anatomopatológicos, é provável que sejamos forçados a redefinir o conceito de CRE, enfocando a relação entre dano endotelial agudo e ativação do complemento.
Subject(s)
Humans , Male , Middle Aged , Raynaud Disease/complications , Vision Disorders/etiology , Acute Kidney Injury/etiology , Kidney/blood supply , Capillaries/metabolism , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Immunohistochemistry , Papilledema/pathology , Dermatomyositis/complications , Dermatomyositis/immunology , Hypertensive Retinopathy/diagnosis , Hypertensive Retinopathy/pathology , Hypertensive Retinopathy/drug therapy , Acute Kidney Injury/diagnosis , Anemia, Hemolytic/diagnosis , Anemia, Hemolytic/etiology , Kidney/pathology , Kidney/diagnostic imagingABSTRACT
Introdução: O sistema complemento é composto por diversas proteínas plasmáticas e é um importante mecanismo de defesa da imunidade inata e adquirida, que exerce funções homeostáticas e fisiológicas, como a remoção de células apoptóticas e complexos imunes. A deficiência neste mecanismo pode ser hereditária ou adquirida, e leva ao aumento da susceptibilidade a doenças infecciosas e não infecciosas, raras e fatais. Objetivo: Descrever as principais causas e consequências da deficiência do sistema complemento e relacioná-las com múltiplas patologias. Material e Métodos: Trata-se de uma revisão bibliográfica narrativa, tendo como base de dados, artigos publicados no Scientific Electronic Library Online (SciELO), National Library of Medicine (PubMed), Medical Literature Analysis and retrieval System Online (MEDLINE), nos últimos 5 anos. Resultados: A associação do complemento e doenças foram observadas em situações de deficiência do sistema complemento, anormalidades na regulação e nas inflamações. Mutações genéticas ou aumento do consumo do complemento levam à ativação imprópria ou excessiva do complemento, podendo conduzir a consequências lesivas e ao desenvolvimento de diversas doenças, como, lúpus eritematoso sistêmico, síndrome urêmica hemolítica atípica, glomerulopatia C3, hemoglobinúria paroxística noturna, glomerulonefrite pós-infecciosas, artrite reumatoide, dentre outras. Conclusão: É evidente a participação do sistema complemento na patogênese e patogenia de diversas doenças. O investimento em pesquisas, que visem ampliar o entendimento do papel do mecanismo do sistema complemento, pode contribuir para o desenvolvimento de intervenções terapêuticas paliativas e ou de cura de diversas doenças, com a consequente melhoria da qualidade de vida dos indivíduos acometidos.
Introduction: The complement system is composed of several plasma proteins and is an important defense mechanism of innate and acquired immunity, which exerts homeostatic and physiological functions, such as the removal of apoptotic cells and immune complexes. Deficiency in this mechanism may be hereditary or acquired, and leads to increased susceptibility to infectious and non-infectious, rare and fatal diseases. Objective: To describe the main causes and consequences of the deficiency of the complement system and to relate them to multiple pathologies. Material and Methods: This is a bibliographical narrative review, based on data published in SciELO (Scientific Electronic Library Online), PubMed (National Library of Medicine), MEDLINE (Medical Literature Analysis and retrieval System Online), last five years. Results:The associations of complement and diseases were observed in situations of deficiency of the complement system, abnormalities in regulation and inflammation. Genetic mutations lead to inappropriate or excessive activation of the complement, as well as increased the consumption of the complement. This can lead to harmful consequences and the development of several diseases, such as systemic lupus erythematosus, atypical hemolytic uremic syndrome, C3 glomerulopathy, nocturnal paroxysmal hemoglobinuria, postpartum glomerulonephritis, infectious diseases, rheumatoid arthritis, among others. Conclusion: The participation of the complement system in the pathogenesis and pathogenesis of several diseases is evident. Investing in research, aimed at broadening the understanding of the role of the complement system mechanism, may contribute to the development of palliative therapeutic interventions and or cure of various diseases, with the consequent improvement in the quality of life of affected individuals.
Subject(s)
Complement System Proteins/deficiency , Disease/etiology , Complement System Proteins/genetics , Complement ActivationABSTRACT
The complement system plays a major role in systemic lupus erythematosus (SLE). At present, complement component 3(C3) and component 4(C4) are the diagnostic markers in the internationally recognized standard of SLE classification. Complement C3 and C4 can play a role in the diagnosis of SLE patients, but they are not very specific diagnostic markers. Therefore, it is important to find more better biomarkers of SLE. In this review, the latest findings in complement-focused research in SLE were explored. Complement level, cell-bound complement activation products and membrane-bound complement regulatory proteins are associated with the pathogenesis of SLE. They may become SLE biomarkers and aid the diagnosis and monitoring of patients with this disease.
ABSTRACT
Thrombotic microangiopathy (TMA) is a group of acute clinical pathological syndromes with common pathological features, which include hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura syndrome. They have many similarities in etiology and clinical presentation. The role of abnormal activation of complement bypass pathway in the genesis and development of HUS has been recognized. More than 100 kinds of complement regulatory factors or gene mutations of complement itself were found to be associated with the development of HUS, which resulted in the decrease of negative complement regulatory protein activity or the increase of complement activation protein function. Abnormal activation of complement system resulted in endothelial injury and thrombosis. Loss of ADAMTS13 activity (<10%) is the most important pathogenesis of TTP. However, there are more and more evidence that complement bypassing pathway is over-regulated and over-activated in the formation of TTP. At present, the research of TMA is focused on finding specific complement-activated biomarkers in patients with various forms of TMA and developing new targeted therapeutic drugs for the disease.
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Antiphospholipid syndrome(APS) is a non-inflammatory autoimmune disease caused by anti-phospholipid antibodies. In recent years, it has been found that over-activation of complement is the key factor leading to the formation of thrombosis and pathological pregnancy in APS. With more understanding of the role of complement activation in the pathogenesis of APS, methods of complement inhibition therapy have emerged one after another. Therefore, the detection of complement components is of great significance for the early diagnosis, treatment and monitoring of APS.
ABSTRACT
Thrombotic microangiopathy (TMA) is an acute clinico-pathological syndrome with varied reasons. Pregnancy related-TMA includes pregnancy associated thrombotic thrombocytopenic purpura (TTP), postpartum hemolytic-uremic syndrome (pHUS), severe preeclampsia (SPE) and Hemolysis, Elevated Liver enzymes and Low Platelet syndrome (HELLP syndrome) and the outcomes are severe. Aberrant activation of complement system plays an important role in the pathogenesis of these diseases. Although these diseases have similar clinical appearance, their pathogenesis, diagnostic and therapeutic methods are different. Precision diagnosis of these diseases to select targeted treatment will greatly improve the prognosis of these patients. Herein, the value of complement system components in the diagnosis and treatment of pregnancy-related TMA are introduced.
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The complement system is an important part of the innate immune system. More evidence showed that the function of complement was not only limited to the elimination of pathogens and other risk factors from the body but also affected the immune escape mechanism of the tumor through different activating pathways. Because of the complex and important role of complement in the tumor, this review expounds the mechanism of complement system participating in immune escape of the tumor from three aspects: complement inherent components, complement activation products and complement regulatory proteins. Additionally, these mechanisms are expected to provide a new application of complement in tumor immunotherapy with immune checkpoint inhibitors.
ABSTRACT
The complement system plays a major role in systemic lupus erythematosus (SLE). At present, complement component 3(C3) and component 4(C4) are the diagnostic markers in the internationally recognized standard of SLE classification. Complement C3 and C4 can play a role in the diagnosis of SLE patients, but they are not very specific diagnostic markers. Therefore, it is important to find more better biomarkers of SLE. In this review, the latest findings in complement-focused research in SLE were explored. Complement level, cell-bound complement activation products and membrane-bound complement regulatory proteins are associated with the pathogenesis of SLE. They may become SLE biomarkers and aid the diagnosis and monitoring of patients with this disease.