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1.
BMC Neurol ; 21(1): 278, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256721

RESUMO

BACKGROUND: Idiopathic intracranial hypertension (IIH) is defined by an increased cerebrospinal fluid pressure in the absence of inflammation, structural obstructions, or mass lesions. Although the underlying pathogenesis of IIH is not fully understood, associations with specific risk factors as obesity, obstruction of cerebral venous sinuses, medications, endocrine or systemic conditions and chronic kidney disease have been described. Immune-complex glomerulonephritis as IgA-nephropathy is a frequent cause of chronic kidney failure, which was reported previously in one IIH patient. To date, there is no knowledge about the variable relation of immune-complex nephritis, kidney function and the course of IIH. CASE PRESENTATION: We report three cases (two females) of concurrent diagnosis of IIH and immune-complex glomerulonephritis. All patients presented with typical IIH symptoms of headache and visual disturbances. Two patients had been diagnosed with IgA-nephropathy only few weeks prior to IIH diagnosis. The third patient had been diagnosed earlier with terminal kidney failure due to a cryoglobulin glomerulonephritis. CONCLUSION: We propose a possible link between renal deposition of immune-complexes and increased cerebrospinal fluid pressure. Pathophysiological hypotheses and clinical implications are discussed. We recommend clinical awareness and further systematic research to obtain more information on the association of IIH and immune-complex glomerulonephritis.


Assuntos
Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico por imagem , Doenças do Complexo Imune/complicações , Doenças do Complexo Imune/diagnóstico por imagem , Pseudotumor Cerebral/complicações , Pseudotumor Cerebral/diagnóstico por imagem , Adulto , Cavidades Cranianas/diagnóstico por imagem , Feminino , Cefaleia/diagnóstico por imagem , Cefaleia/etiologia , Humanos , Masculino , Obesidade/complicações , Obesidade/diagnóstico por imagem , Fatores de Risco , Transtornos da Visão/diagnóstico por imagem , Transtornos da Visão/etiologia , Adulto Jovem
2.
Front Immunol ; 12: 582768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177880

RESUMO

Background: The presence of fluid attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated cerebral cortical encephalitis with seizures (FLAMCES) was recently reported. However, the clinical characteristics and outcome of this rare clinico-radiographic syndrome remain unclear. Methods: The present study reported two new cases. In addition, cases in the literature were systematically reviewed to investigate the clinical symptoms, magnetic resonance imaging (MRI) abnormalities, treatments and prognosis for this rare clinico-radiographic syndrome. Results: A total of 21 cases were identified during a literature review, with a mean patient age at onset of 26.8 years. The primary clinicopathological characteristics included seizures (100%), headache (71.4%), fever (52.3%) and other cortical symptoms associated with the encephalitis location (61.9%). The common seizure types were focal to bilateral tonic-clonic seizures (28.6%) and unknown-onset tonic-clonic seizures (38.1%). The cortical abnormalities on MRI FLAIR imaging were commonly located in the frontal (58.8%), parietal (70.6%) and temporal (64.7%) lobes. In addition, pleocytosis in the cerebrospinal fluid was reported in the majority of the patients (95.2%). All patients received a treatment regimen of corticosteroids and 9 patients received anti-epileptic drugs. Clinical improvement was achieved in all patients; however, one-third of the patients reported relapse following recovery from cortical encephalitis. Conclusions: FLAMCES is a rare phenotype of MOG-associated disease. Thus, the wider recognition of this rare syndrome may enable timely diagnosis and the development of suitable treatment regimens.


Assuntos
Autoanticorpos/metabolismo , Córtex Cerebral/patologia , Líquido Cefalorraquidiano/imunologia , Encefalite/diagnóstico , Doenças do Complexo Imune/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Anticonvulsivantes/uso terapêutico , Córtex Cerebral/imunologia , Encefalite/tratamento farmacológico , Feminino , Cefaleia , Humanos , Doenças do Complexo Imune/tratamento farmacológico , Leucocitose , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito , Convulsões , Adulto Jovem
3.
Cornea ; 40(8): 1067-1069, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34029243

RESUMO

ABSTRACT: We present 2 cases of striking stromal corneal infiltrates months after COVID-19 infection. While we cannot prove that these infiltrates are caused by or directly related to COVID-19, we did not find any other plausible cause that could explain these ophthalmic signs. In these cases, the ongoing process was detected in relatively early stages due to scheduled visits with patients and responded positively to prednisolone acetate 1% ophthalmic suspension. However, we do not know the response to treatment in more advanced cases.


Assuntos
COVID-19/diagnóstico , Doenças da Córnea/diagnóstico , Substância Própria/patologia , Infecções Oculares Virais/diagnóstico , SARS-CoV-2 , COVID-19/tratamento farmacológico , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Doenças da Córnea/tratamento farmacológico , Doenças da Córnea/virologia , Infecções Oculares Virais/tratamento farmacológico , Infecções Oculares Virais/virologia , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Glucocorticoides/uso terapêutico , Humanos , Doenças do Complexo Imune/diagnóstico , Doenças do Complexo Imune/tratamento farmacológico , Doenças do Complexo Imune/virologia , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , SARS-CoV-2/imunologia , Uveíte/diagnóstico
4.
Scand J Immunol ; 93(3): e12994, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33151588

RESUMO

Some pathogen infections and immune system deficiencies have been linked to a few autoimmune diseases. However, the pathogenesis of most autoimmune diseases is unknown. An explanatory hypothesis for the pathogenesis of infection-initiated autoimmune diseases is provided. Virulent pathogen infections create extensive pathogen antigens that frequently require antibodies. These antibodies create extensive antigen-antibody immune complexes, which some immuno-compromised individuals will not adequately eliminate. This will cause inflammatory type III hypersensitivity symptoms, including protease releases that destroy epithelium, mesothelium and endothelium basement membranes, express new immunogenic antigens from previously sequestered basement membrane constituents, and ultimately induce new autoantibodies. This can continue after the infection ends, if the first wave of protease attacks on basement membranes induces new autoantibodies that cause new uncleared antigen-antibody immune complexes and type III hypersensitivity reactions. The secreted proteases and other enzymes will have preferred substrates and these proteases or other enzymes by themselves, or by their processed protein substrates, can express immunogenic antigens that induce new autoantibodies and initiate various autoimmune diseases. In summary, several autoimmune diseases can be initiated in immuno-compromised individuals during extensive pathogen infections, if these individuals have two immune problems: (a) slow or weak initial immune responses that result in a reliance on antibodies and (b) an inability to eliminate the resulting antigen-antibody immune complexes by phagocytosis. These two immune problems and the resulting immune system type III hypersensitivity reaction can explain the causation of several autoimmune diseases, including the most common and the rarest autoimmune diseases, both their differences and their similarities.


Assuntos
Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Hospedeiro Imunocomprometido/imunologia , Síndromes de Imunodeficiência/imunologia , Infecções/imunologia , Complexo Antígeno-Anticorpo/imunologia , Autoanticorpos/imunologia , Humanos , Doenças do Complexo Imune/imunologia , Doenças do Complexo Imune/patologia
5.
Rev. méd. Minas Gerais ; 31: E0032, 2021.
Artigo em Português | LILACS | ID: biblio-1291379

RESUMO

Introdução: A Síndrome Stevens-Johnson (SSJ) é uma doença causada por hipersensibilidade a imunocomplexos e pode ser desencadeada por distintos fármacos, dentre eles a fenitoína. Devido sua complexidade e raridade, ainda nãohá consenso de tratamento padrão ouro, porém sabese da necessidade da atuação multidisciplinar. Para os cuidados com as feridas, pode-se citar os curativo se a fotobiomodulação (FBM). Objetivo: Relatar o uso da FBM como terapia complementar em um caso de SSJ no Hospital Universitário Regional dos Campos Gerais (HU-UEPG). Métodos: Paciente sexo feminino, 26 anos, deu entrada na unidade de terapia intensiva (UTI) com diagnóstico de SSJ secundária ao uso de fenitonína, escore de SCORTEN 1, com área sem epitélio íntegro 10- 30% e área acometida por lesões de 94,5%, poupando apenas o couro cabeludo. Foi abordada e tratada por uma equipe multidisciplinar e solicitado vaga em centro de especializado em queimados. No sétimo dia de UTI foi iniciado tratamento com FBM, 2 J por ponto, distância entre pontos de 2cm, comprimento onda vermelho (660nm), nas feridas que não apresentavam secreção, foram cinco sessões com intervalo de três dias entre a terceira e a quarta. Resultados: A paciente apresentou melhora visível das lesões cutâneas e recebeu alta hospitalar 5 dias após cessação da FBM. Conclusão: O uso da FBM pode ser efetiva no tratamento complementar da fase aguda SSJ desencadeada por fenitoína.


Introduction: Stevens-Johnson Syndrome (SJS) is a disease caused by hypersensitivity to immune complexes and can be triggered by different drugs, including phenytoin. Due to its complexity and rarity, there is still no consensus on gold standard treatment, but the need for multidisciplinary action is known. For wound care, dressings and photobiomodulation (PBM) can be mentioned. Objective: This study is to report the use of PBM as complementary therapy in a case of SJS at Hospital Universitário Regional dos Campos Gerais (HU-UEPG). Methods: A 26-year-old female patient was admitted to the intensive care unit (ICU) diagnosed with SJS secondary to the use of phenytoin, SCORTEN score 1, with an area without intact epithelium 10-30% and an area affected by injuries of 94.5 %, saving only the scalp. She was approached and treated by a multidisciplinary team which requested a place in a specialized burn center. On the seventh day of ICU, treatment with PBM, 2J per point was started, distance between points of 2cm, red wave length (660nm), in wounds that did not present secretion, with a total of five sessions with an interval of three days between the third and fourth. Results: The patient showed a visible improvement of skin lesions and was discharged from hospital 5 days after cessation of PBM. Conclusion: Use of PBM can be effective in complementary treatment of acute SJS phase triggered by phenytoin.


Assuntos
Humanos , Feminino , Adulto , Síndrome de Stevens-Johnson , Terapia com Luz de Baixa Intensidade , Fenitoína , Couro Cabeludo , Ferimentos e Lesões , Modalidades de Fisioterapia , Doenças do Complexo Imune
6.
Saudi J Kidney Dis Transpl ; 31(5): 1101-1105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33229775

RESUMO

Filarial glomerular disease has been attributed to circulating immune complex deposition. We report here a rare manifestation of filarial nephropathy with microfilariae documented in glomerular capillaries in addition to immune complex glomerulonephritis, thus suggesting that direct toxicity may also contribute to the pathogenesis of this entity.


Assuntos
Filariose Linfática , Glomerulonefrite , Doenças do Complexo Imune , Glomérulos Renais , Humanos , Glomérulos Renais/parasitologia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade
7.
Rev. esp. enferm. dig ; 112(9): 682-687, sept. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-200063

RESUMO

INTRODUCCIÓN: las manifestaciones pancreáticas en enfermedad inflamatoria intestinal (EII) incluyen principalmente pancreatitis aguda secundaria a fármacos y, con menor frecuencia, pancreatitis autoinmune. Existe asimismo una asociación particular con la pancreatitis autoinmune tipo 2. MÉTODOS: estudio retrospectivo de pacientes con diagnóstico de colitis ulcerosa (CU) y pancreatitis autoinmune (PAI) en control en dos centros en Santiago de Chile, entre los años 2007 y 2018. Se registraron datos clínicos, resultados de laboratorio e imágenes, evolución en el tiempo y tratamientos utilizados. RESULTADOS: se identificaron 12 pacientes con ambas enfermedades, la edad promedio fue 34 años, con un 42 % de sexo masculino. En todos los casos se estableció el diagnóstico probable de PAI tipo 2 en base a la resonancia magnética (RM) de páncreas, la asociación con EII y la rápida respuesta a tratamiento con corticoides. En dos casos se tomaron muestras para estudio histológico pero el resultado fue no concluyente. Se observó recurrencia de la PAI en un solo caso. El 58 % de los pacientes tenían una CU extensa, el 100 % recibe tratamiento con 5-ASA y el 33 %, con azatioprina. Solo un paciente tuvo un brote grave y ninguno presentó complicaciones, necesidad de tratamiento con biológicos ni cirugía. CONCLUSIÓN: en nuestra casuística se confirma la asociación entre CU y PAI tipo 2. No se observó mayor severidad de la EII en este grupo de pacientes


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Doenças do Complexo Imune/complicações , Colite Ulcerativa/complicações , Pancreatite/complicações , Estudos Retrospectivos
8.
J Vet Emerg Crit Care (San Antonio) ; 30(5): 574-580, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32652787

RESUMO

OBJECTIVE: To describe 2 dogs with acute kidney injury secondary to type III hypersensitivity reaction to 25% human serum albumin (HSA). CASE SERIES SUMMARY: Two dogs were presented with evidence of septic peritonitis. The dogs were hospitalized following definitive surgical correction of a jejunal laceration following routine ovariohysterectomy, and removal of a jejunal foreign body. In the postoperative period, both dogs developed hypoalbuminemia and received 25% HSA. At the time of initial discharge, both dogs were doing well clinically and had normal renal parameters. Eleven and 18 days after HSA infusion, respectively, both dogs were re-presented with clinical signs of inappetence, vomiting, and lameness that progressed to urticaria, peripheral and angioedema, and petechiae, consistent with a delayed type III hypersensitivity reaction. Treatment for the type III hypersensitivity reaction to HSA included administration of diphenhydramine and glucocorticoids. Despite partial resolution of edema and joint swelling, both dogs developed progressive azotemia together with hypoalbuminemia and proteinuria. One dog developed an anuric acute kidney injury (AKI). Both dogs were humanely euthanized. Histopathology of the kidneys of both dogs was consistent with immune complex deposition and vasculitis. NEW OR UNIQUE INFORMATION: Severe type III hypersensitivity reactions have been documented in healthy dogs and clinical patients following the administration of HSA. This report describes the first documented delayed type III hypersensitivity reaction in 2 dogs with septic peritonitis that resulted in AKI, glomerulonephritis, and oligo- to anuria in clinical patients following administration of 25% HSA.


Assuntos
Injúria Renal Aguda/veterinária , Doenças do Cão/induzido quimicamente , Hipoalbuminemia/veterinária , Albumina Sérica Humana/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Animais , Doenças do Cão/etiologia , Doenças do Cão/terapia , Cães , Feminino , Humanos , Hipersensibilidade/veterinária , Hipoalbuminemia/etiologia , Hipoalbuminemia/terapia , Doenças do Complexo Imune/veterinária , Masculino , Peritonite/complicações , Peritonite/veterinária , Proteinúria/veterinária , Albumina Sérica Humana/uso terapêutico , Vasculite/veterinária
9.
Inflammopharmacology ; 28(5): 1219-1222, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32638151

RESUMO

SARS-CoV-2, a new virus that appeared in Wuhan, China, in 2019 has approximately an 80% genomic match to the Severe Acute Respiratory Symptom (SARS) virus, which is known to come from a bat virus. Symptoms of Kawasaki disease in general and incomplete Kawasaki disease have been seen in a subset of pediatric patients having a current or previous infection of SARS-CoV-2. A viral infection, such as a SARS-CoV-2 virus infection, could result in extensive antigen-antibody immune complexes that cannot be quickly cleared in a subset of patients and thus create a type III hypersensitivity immune reaction and cause Kawasaki disease or Kawasaki disease symptoms (also known as multisystem inflammatory syndrome) in a subset of patients. Extensive binding of antibodies to viral antigens can create antigen-antibody immune complexes, which, if not eliminated in certain individuals having dysfunctional complement systems, can start inflammatory type III hypersensitivity symptoms, including protease releases that can disrupt epithelium, mesothelium, and endothelium basement membranes, and induce pervasive inflammation throughout the body. This could continue after SARS-CoV-2 infections end if the first wave of protease attacks on basement membranes created new secondary autoantibodies and new uncleared antigen-antibody immune complexes.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Síndrome de Linfonodos Mucocutâneos/etiologia , Síndrome de Linfonodos Mucocutâneos/virologia , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Complexo Antígeno-Anticorpo , Membrana Basal/imunologia , Membrana Basal/patologia , COVID-19 , Criança , Humanos , Doenças do Complexo Imune/imunologia , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Pandemias , Peptídeo Hidrolases/química , Pele/patologia , Síndrome de Resposta Inflamatória Sistêmica/terapia
10.
Clin Nephrol ; 94(2): 97-102, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32567542

RESUMO

Staphylococcus infection-associated glomerulonephritis (SAGN) is characterized by the presence of IgA and C3 as the predominant components present in the glomerular immune deposits. Glomerulonephritis frequently resolves after effective treatment of the staphylococcal infection. However, there have been few studies of repeat kidney biopsy after resolution of glomerulonephritis. We present a combined kidney-pancreas transplant patient who developed SAGN due to Staphylococcus aureus bacteremia from an old infected arteriovenous (AV) graft, which occurred after a long period of stable allograft function. Clinical improvement occurred following surgical debridement and appropriate antibiotics with subsequent clearance of bacteremia. However, 3 weeks later he presented with severe acute kidney injury related to rapidly progressive glomerulonephritis. Renal allograft biopsy revealed immune complex glomerulonephritis with predominance of IgA and C3 in subendothelial and mesangial deposits, consistent with SAGN. There was no evidence for recurrent staphylococcal infection. High-dose steroid therapy was followed by resolution of hematuria and improvement in allograft function with gradual return of serum creatinine concentration to near baseline levels. However, 1 year after the diagnosis of SAGN, he developed gradually worsening allograft function with persistent proteinuria. Repeat allograft biopsy showed sclerosing glomerular changes and extensive interstitial fibrosis and tubular atrophy. There was complete resolution of proliferative changes, and IgA and C3 deposits were no longer detectable. Despite transient allograft function stabilization, the patient progressed to end-stage renal disease (ESRD), and maintenance hemodialysis was reinitiated 2.5 years after the diagnosis of SAGN. Pancreatic allograft function remained normal.


Assuntos
Complemento C3/análise , Glomerulonefrite , Imunoglobulina A/sangue , Transplante de Rim , Infecções Estafilocócicas , Bacteriemia , Humanos , Doenças do Complexo Imune , Masculino
12.
Clin Immunol ; 217: 108493, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32526273

Assuntos
Complexo Antígeno-Anticorpo/biossíntese , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Doenças do Complexo Imune/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Vasculite/imunologia , Anticorpos Antivirais/biossíntese , Complexo Antígeno-Anticorpo/efeitos dos fármacos , Betacoronavirus/imunologia , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/imunologia , Vasos Sanguíneos/patologia , Vasos Sanguíneos/virologia , COVID-19 , Complemento C3/antagonistas & inibidores , Complemento C3/biossíntese , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Humanos , Doenças do Complexo Imune/complicações , Doenças do Complexo Imune/tratamento farmacológico , Doenças do Complexo Imune/virologia , Imunidade Humoral/efeitos dos fármacos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Receptores de Interleucina-1/antagonistas & inibidores , Receptores de Interleucina-1/biossíntese , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Vasculite/complicações , Vasculite/tratamento farmacológico , Vasculite/virologia
13.
Clin Immunol ; 217: 108487, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32479986

RESUMO

Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Doenças do Complexo Imune/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Células Th2/imunologia , Vasculite/imunologia , Idoso , Anticorpos Antivirais/biossíntese , Complexo Antígeno-Anticorpo/biossíntese , Betacoronavirus/imunologia , Vasos Sanguíneos/imunologia , Vasos Sanguíneos/patologia , Vasos Sanguíneos/virologia , COVID-19 , Complemento C3/biossíntese , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Progressão da Doença , Células Endoteliais/imunologia , Células Endoteliais/patologia , Células Endoteliais/virologia , Humanos , Doenças do Complexo Imune/complicações , Doenças do Complexo Imune/virologia , Imunidade Humoral , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Interleucina-6/biossíntese , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/virologia , Células Th2/patologia , Células Th2/virologia , Vasculite/complicações , Vasculite/virologia
14.
CEN Case Rep ; 9(4): 344-346, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32372346

RESUMO

Hereditary C2 deficiency is the most common early complement deficiency and characterized by recurrent infections and autoimmunity despite most patients are also asymptomatic. Type I hereditary C2 deficiency is caused by a heterozygous deletion in C2 gene resulting in early stop codon and lack of C2 production. Clinical spectrum may vary and pure nephrological involvement without the presence of recurrent infections is scarce in hereditary C2 deficiency.We report here a previously healthy 14-year-old boy presenting recurrent self-limited macroscopic hematuria and persistently low serum C4 levels, diagnosed as having type I hereditary C2 deficiency with confirming a novel heterozygote deletion (c.1567 + 22_1567 + 43del) in C2 gene. He has been remained asymptomatic for the next 18 months. Since the diagnosis of C2 deficiency was made in the absence of organ-threatening involvement such as immune complex-mediated glomerulonephritis, we think that early diagnosis and optimal follow-up may improve life-span of the patients with hereditary early complement deficiencies.


Assuntos
Complemento C2/deficiência , Hematúria/etiologia , Doenças da Deficiência Hereditária de Complemento/diagnóstico , Adolescente , Assistência ao Convalescente , Complemento C2/genética , Complemento C4/análise , Diagnóstico Precoce , Glomerulonefrite/imunologia , Hematúria/diagnóstico , Doenças da Deficiência Hereditária de Complemento/classificação , Doenças da Deficiência Hereditária de Complemento/imunologia , Heterozigoto , Humanos , Doenças do Complexo Imune/etiologia , Masculino , Recidiva
15.
Sci Rep ; 10(1): 5210, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251357

RESUMO

Estrogens have been shown to regulate the immune system and modulate multiple autoimmune diseases. 17α-ethinyl estradiol (EE), a synthetic analog of 17ß-estradiol, is prescribed commonly and found in oral contraceptives and hormone replacement therapies. Surprisingly, few studies have investigated the immunoregulatory effects of exposure to EE, especially in autoimmunity. In this study, we exposed autoimmune-prone female MRL/lpr mice to a human-relevant dose of EE through the oral route of exposure. Since lupus patients are prone to infections, groups of mice were injected with viral (Imiquimod, a TLR7 agonist) or bacterial (ODN 2395, a TLR9 agonist) surrogates. We then evaluated autoimmune disease parameters, kidney disease, and response to in vivo TLR7/9 pathogenic signals. EE-exposed mice had increased proteinuria as early as 7 weeks of age. Proteinuria, blood urea nitrogen, and glomerular immune complex deposition were also exacerbated when compared to controls. Production of cytokines by splenic leukocytes were altered in EE-exposed mice. Our study shows that oral exposure to EE, even at a very low dose, can exacerbate azotemia, increase clinical markers of renal disease, enhance glomerular immune complex deposition, and modulate TLR7/9 cytokine production in female MRL/lpr mice. This study may have implications for EE-exposure risk for genetically lupus-prone individuals.


Assuntos
Etinilestradiol/toxicidade , Doenças do Complexo Imune/imunologia , Nefrite Lúpica/imunologia , Glicoproteínas de Membrana/agonistas , Receptor 7 Toll-Like/agonistas , Receptor Toll-Like 9/agonistas , Animais , Autoanticorpos/análise , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Citocinas/biossíntese , Etinilestradiol/administração & dosagem , Feminino , Imiquimode/farmacologia , Doenças do Complexo Imune/induzido quimicamente , Doenças do Complexo Imune/tratamento farmacológico , Doenças do Complexo Imune/genética , Imunoglobulina G/análise , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Leucócitos/metabolismo , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/tratamento farmacológico , Camundongos , Camundongos Endogâmicos MRL lpr , Proteinúria/etiologia , Baço/patologia
16.
PLoS One ; 15(4): e0231655, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32325480

RESUMO

Despite the potential for the chemokine class as therapeutic targets in immune mediated disease, success has been limited. Many chemokines can bind to multiple receptors and many receptors have multiple ligands, with few exceptions. One of those exceptions is CCL20, which exclusively pairs to CCR6 and is associated with several immunologic conditions, thus providing a promising therapeutic target. Following successful evaluation in a single dose, first time in human clinical study, GSK3050002-a humanized IgG1 monoclonal antibody against human CCL20-was evaluated in a 26-week cynomolgus monkey toxicology study. A high incidence of unexpected vascular and organ inflammation was observed microscopically, leading to the decision to halt clinical development. Here we report a dose-responsive increase in the incidence and severity of inflammation in multiple organs from monkeys receiving 30 and 300 mg/kg/week by either subcutaneous or intravenous injection. Histomorphological changes resembled an immune complex-mediated pathology, which is often due to formation of anti-drug antibodies in monkeys receiving a human protein therapeutic and thus not predictive of clinical outcome. However, the presentation was atypical in that there was a clear dose response with a very high incidence of inflammation with a low incidence of ADA that did not correlate well individually. Additionally, the immunohistologic presentation was atypical in that the severity and distribution of tissue inflammation was greater than the numbers of associated immune complexes (i.e., granular deposits). An extensive ex vivo analysis of large molecular weight protein complexes in monkey serum from this study and in human serum samples demonstrated a time-dependent aggregation of GSK3050002, that was not predicted by in vitro assays. The aggregates also contained complement components. These findings support the hypothesis that immune complexes of drug aggregates, not necessarily including anti-drug antibodies, can fix complement, accumulate over time, and trigger immune complex disease. A situation which may have increased clinical relevance than typical anti-drug antibody-associated immune complex disease in monkeys administered human antibody proteins.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Quimiocina CCL20/imunologia , Proteínas do Sistema Complemento/imunologia , Doenças do Complexo Imune/tratamento farmacológico , Doenças do Complexo Imune/imunologia , Imunoconjugados/uso terapêutico , Animais , Anticorpos Monoclonais/toxicidade , Doença Crônica , Cristalização , Determinação de Ponto Final , Feminino , Humanos , Inflamação/imunologia , Inflamação/patologia , Macaca fascicularis
18.
Expert Rev Gastroenterol Hepatol ; 14(2): 113-125, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31951758

RESUMO

Introduction: Multiple studies have revealed a strong relationship between the development of nephropathy and hepatitis B virus (HBV) infection. The underlying pathogenesis of hepatitis B-related glomerulonephritis (HBV-GN) involves immune complexes, which can be isolated from kidney tissues. Clearance of HBV antigenemia improves renal impairment and proteinuria in HBV-GN patients.Areas covered: In this review, we present our current understanding of the epidemiology, pathogenesis, pathology, diagnosis, and treatment of HBV-GN. We discuss the advantages and disadvantages of oral nucleoside/nucleotide analogs (NAs), and the main pharmaceutical treatment for hepatis B.Expert opinion: Currently, antiviral agents are the main HBV-GN therapeutic agents. Although no randomized controlled clinical trials have compared the efficacy of interferon (IFN) and NA, we suggest IFN treatment for pediatric patients (IFN-α in patients ≥1 year; pegIFN-α in patients ≥3 years) considering treatment duration and absence of resistance. Novel NAs have brought about promising treatment options involving high efficacy viral suppression and low resistance rates. NAs with a high barrier to resistance (e.g. entecavir) are recommended as first-line therapy of HBV-GN. Immunosuppression monotherapy, such as corticosteroids, is of little benefit and potentially harmful to HBV-GN patients due to the possibility of viral reactivation.


Assuntos
Glomerulonefrite/diagnóstico , Glomerulonefrite/tratamento farmacológico , Hepatite B Crônica/imunologia , Complexo Antígeno-Anticorpo/imunologia , Antivirais/uso terapêutico , Glomerulonefrite/epidemiologia , Glomerulonefrite/etiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Doenças do Complexo Imune/imunologia , Doenças do Complexo Imune/patologia , Doenças do Complexo Imune/virologia , Imunossupressores/uso terapêutico , Interferon-alfa/uso terapêutico , Rim/imunologia , Rim/patologia , Nucleosídeos/efeitos adversos , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico
19.
BMC Vet Res ; 15(1): 303, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429743

RESUMO

BACKGROUND: Chronic kidney disease (CKD) has typically a non-immune mediated origin in cats and immune-complex glomerulonephritis (ICGN) is scarcely described. Aims of this study were to characterize ICGN by light and electron microscopy and identify associations with clinico-pathological findings. In addition, comparisons between cats with ICGN and non immune-complex glomerulonephritis (non-ICGN) were performed. Renal samples examined between 2010 and 2019 were considered if both light and electron microscopy were performed. Signalment, feline immunodeficiency virus (FIV) and leukemia virus (FeLV) status, serum creatinine concentration, urine protein-to-creatinine (UPC) ratio, systolic blood pressure (SBP) and International Renal Interest Society (IRIS) stage were retrieved and used for comparisons. RESULTS: Sixty-eight client-owned cats were included. Thirty-seven cats (54.4%) had ICGN and 31 (45.6%) non-ICGN. Eighteen (48.6%) with ICGN had membranous glomerulonephropathy (MGN), 14 (37.8%) membranoproliferative glomerulonephritis (MPGN), and 5 (13.5%) mesangioproliferative glomerulonephritis (MeGN). Clinico-pathological data were not associated with any type of ICGN. Among cats with non-ICGN, 11 (35.5%) had end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal mesangiosclerosis, 2 (6.5%) glomerular atrophy, 2 (6.5%) renal dysplasia and 1 (3.1%) amyloidosis. Eight (25.8%) cats with non-ICGN had chronic interstitial nephritis (CIN) grade 1, 13 (41.9%) grade 2 and 10 (32.3%) grade 3; creatinine and UPC ratio increased with CIN grades (p = 0.001, p < 0.001). Cats with ICGN were more frequently FIV or FeLV-infected (OR:11.4; 95%CI:1.4-94.4; p = 0.024), had higher UPC ratio (OR:6.8; 95%CI:2.5-18.2; p < 0.001) and were younger (OR:0.9; 95%CI:0.7-1.0; p = 0.042) than cats with non-ICGN. CONCLUSIONS: MGN and MPGN were the most common morphological diagnoses of ICGN in cats. Unfortunately, none of the investigated findings differentiated ICGN morphological diagnoses. Serum creatinine concentration and UPC ratio were directly associated with grades of CIN (p = 0.001 and p < 0.001, respectively), confirming previous literature. More ICGN than non-ICGN was observed in cats with retroviral infections, younger cats and higher UPC ratio.


Assuntos
Doenças do Gato/patologia , Glomerulonefrite/veterinária , Doenças do Complexo Imune/veterinária , Animais , Gatos , Feminino , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Doenças do Complexo Imune/patologia , Rim/patologia , Masculino , Estudos Retrospectivos
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