Immunomodulation of Autoimmune and Inflammatory Diseases with Intravenous Immune Globulin

Kazatchkine, Michel D.; Kaveri, Srini V.

doi:10.1056/nejmra993360

Cited by 1,110 publications

(876 citation statements)

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“…One theory is that they could inhibit inflammation, leading to a decrease of endoneurial pressure and oedema, which cause ischaemia in nerve trunks. 25 CMAP 0·25 (0·10-0·64; p=0·004), and cytomegalovirus infection 0·23 (0·08-0·69; p=0·009). We did not note any significant treatment interactions in either multivariate analysis and, therefore, no subgroups were detected in which the effect of methylprednisolone was better than placebo.…”

Section: Discussionmentioning

confidence: 99%

Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome: randomised trial

Koningsveld¹,

Schmitz²,

Meché³

et al. 2004

The Lancet

332

197

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SummaryBackground Despite available treatment with intravenous immunoglobulin (IVIg), morbidity and mortality are considerable in patients with Guillain-Barré syndrome (GBS). Our aim was to assess whether methylprednisolone, when taken with IVIg, improves outcome when compared with IVIg alone.Methods We did a double-blind, placebo-controlled, multicentre, randomised study, to which we enrolled patients who were unable to walk independently and who had been treated within 14 days after onset of weakness with IVIg (0·4 g/kg bodyweight per day) for 5 days. We assigned 233 individuals to receive either intravenous methylprednisolone (500 mg per day; n=116) or placebo (n=117) for 5 days within 48 h of administration of first dose of IVIg. Because age is an important prognostic factor, we split treatment groups into two age-groups-ie, younger than age 50 years, or 50 years and older. Our primary outcome was an improvement from baseline in GBS disability score of one or more grades 4 weeks after randomisation. Analysis was by intention to treat.Findings We analysed 225 patients. GBS disability scores increased by one grade or more in 68% (76 of 112) of patients in the methylprednisolone group and in 56% (63 of 113) of controls (odds ratio [OR] 1·68, 95% CI 0·97-2·88; p=0·06). After adjustment for age and degree of disability at entry, treatment OR was 1·89 (95% CI 1·07-3·35; p=0·03). Side-effects did not differ greatly between groups.Interpretation We noted no significant difference between treatment with methylprednisolone and IVIg and IVIg alone. Because of the relevance of prognostic factors and the limited side-effects of methylprednisolone, the potential importance of combination treatment with the drug and IVIg, however, warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome: randomised trial

Koningsveld¹,

Schmitz²,

Meché³

et al. 2004

The Lancet

332

197

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“…Por su parte, está establecido que la IGIV regula los clones autorreactivos de linfocitos b 8,9 , controlando así la proliferación de éstos y modulando la producción de autoanticuerpos 10 . El bloqueo competitivo, es decir, la unión de la IgG proveniente de la IGIV en vez de los autoanticuerpos propios de los pacientes con vitiligo a los receptores FcγR en macrófagos, previene el clearance de los melanocitos sensibilizados (realizado por el sistema retículoendotelial), siendo considerado como el mecanismo clave de la IGIV en el control de las patologías mediadas por anticuerpos 1,4,8,9,[11][12][13] . En la piel con vitiligo destaca la presencia de LT cD8+ citotóxicos infiltrados en el área perilesional 5,6 y adyacentes a los melanocitos desaparecidos 15 .…”

Section: Discussionunclassified

“…a su vez, en los preparados de IGIV se han pesquisado anticuerpos anti-idiotipo que son capaces de unirse a la región variable del TcR (T-cell receptor), bloqueando su activación por autoantígenos; también están presentes anticuerpos naturales contra las molécula cD4, cD8 y contra una secuencia conservada de las moléculas de histocompatibilidad tipo I y II, que bloquean la proliferación de LT cD4 y cD8 respectivamente. La IGIV, a su vez, restaura el balance entre células Th1 y Th2 en enfermedades autoinmunes en las que la población de células autorreactivas Th1 o Th2 se encuentra expandida, al controlar su proliferación y modular su activación y la síntesis de citoquinas 12,13 .…”

Section: Discussionunclassified

Vitiligo y terapia con inmunoglobulina intravenosa: a propósito de un paciente con síndrome de Sjögren

2011

Rev. méd. Chile

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Remission of vitiligo during treatment with intravenous immunoglobulin. Report of one caseVitiligo is associated with other autoimmune diseases. We report a 52-year-old male with a Sjögren syndrome that was treated with monthly pulses of intravenous immunoglobulin for a chronic inflammatory demyelinating polyradiculoneuropathy. The neurological disorder responded adequately to the treatment and the patient also noted a marked remission of his vitiligo with almost compete re-pigmentation of the scalp and face and partial re-pigmentation of other areas. (Rev Med Chile 2011; 139: 484-488 E l vitiligo es un trastorno de la pigmentación cutánea, caracterizado por la presencia de áreas de piel despigmentada, secundario a la pérdida crónica y progresiva de los melanocitos epidérmicos. a nivel mundial tendría una prevalencia entre 0,5-2% según las diferentes series, aunque en estudios recientes se ha sugerido que esta cifra podría estar sobrestimada 1 .Su etiología es aún incierta, sin embargo, ha sido establecido que en pacientes genéticamente susceptibles, factores como la autoinmunidad, las infecciones, el estrés, anormalidades neurológicas, disfunciones en el receptor de la melatonina, de la migración del melanocito y de origen tóxico, entre otros, podrían tener un rol patogénico 2 .En relación al proceso autoinmune, existiría participación directa del sistema inmunológico, tanto de la rama humoral como celular. La primera se caracteriza por presencia de anticuerpos contra múltiples antígenos expresados en los melanocitos y la segunda por el reclutamiento de linfocitos T (LT) cD8+ citotóxicos y macrófagos. Posiblemente, la destrucción inicial de los melanocitos sería consecuencia de la acumulación de metabolitos tóxicos y posterior amplificación autoinmune del daño sobre éstos.clínicamente puede manifestarse en forma segmentaria o difusa, asociándose esta última variedad a diversas enfermedades autoinmunes, entre las que destacan la tiroiditis de Hashimoto, el lupus eritematoso sistémico y la anemia perniciosa. Estas etiologías autoinmunes representan 30% del total de pacientes con la forma difusa 2 .Desde el punto de vista psicosocial, el vitiligo puede tener un alto impacto en la autoestima y calidad de vida del paciente afectado, incluso mayor al asociado con la psoriasis. actualmente, disponemos de diversas aproximaciones terapéuticas para esta patología, las que dependen principalmente de la extensión del compromiso cutáneo y del tipo de piel, sin embargo, no existe hasta el momento un tratamiento completamente efectivo 3 .La terapia con inmunoglobulina intravenosa (IGIV) posee un complejo mecanismo de acción. Someramente podemos resumir sus funciones en: modulación de la expresión y función de los receptores Fc, interferencia con la activación del complemento y la red de citoquinas, provisión de anticuerpos anti-idiotipo, modulación de las células dendríticas e interferencia con la activación y función de los linfocitos b y T, siendo esta última,

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“…Later it was used for the first time for an autoimmune disease, idiopathic thrombocytopenic purpura. Since then, this type of therapy has been used in different immunoinflammatory disorders, such as systemic lupus erythematosus, juvenile rheumatoid arthritis, and Guillain-Barré 6 . The mechanisms of action and the side effects have not yet been totally elucidated, and the real efficacy in controlled clinical trials is yet to be revealed.…”

Section: Discussionmentioning

confidence: 99%

Insuficiência renal aguda após uso de imunoglobulina intravenosa para tratamento de miocardite

Pordeus¹,

Tostes²,

Mesquita³

et al. 2005

Arq. Bras. Cardiol.

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The patient is a 60-year-old female with functional class III/ IV (NYHA) heart failure of an immunomediated etiology (autoimmune myocarditis). After unsuccessful therapeutic attempts, intravenous immunoglobulin was used, leading to deterioration in renal function, a rare complication of that therapy. After hemodialysis, the patient's renal function was restored, and the chronic heart failure improved to functional class I.Myocardites constitute a group of diseases characterized by immuno-inflammatory aggression against the myocardium. The anatomicopathological substrate of this aggression has been classically described as a cellular infiltration of lymphocytes, macrophages, and other leukocytes, with destruction of cardiomyocytes, myocytolysis (Dallas criteria) 1 . In past years, advances in understanding of the complex pathophysiology of the disease and low sensitivity of the histopathological criteria have forced us to widen the model of aggression to beyond the immune response of the classical cellular type (Th1). Currently, we believe that an immunomediated aggression against the myocardium occurs, even when the infiltration of immunologic cells is absent. The characterization of pathogenic autoantibodies specific for more than a dozen autoantigens has led us to a new model 2 . The etiology of those diseases is still obscure. Activation of the immunologic system is known to occur, resulting in different forms of myocardial injury. The pathogenic stimuli that lead to the development of that cardiospecific aggression are yet to be elucidated.The current major hypothesis is based on the model of viral infection as the promoter of the immune reaction directed against the heart. Different types of viruses, such as coxsackievirus, parvovirus, adenovirus, cytomegalovirus, Epstein-Barr virus, and parvovirus B19, have often been implicated. However, most clinical studies have shown great variability and low positivity in evidencing the viruses 1 . Other clinical phenomena, such as skin diseases (eg, psoriasis and vitiligo), systemic autoimmune diseases, and even intestinal diseases, such as celiac disease, have been significantly associated with myocardites, suggesting, therefore, a wide and complex pathophysiological model 3 .The clinical findings of myocardites are highly varied. Their symptoms may range from fever and malaise to cardiac symptoms, such as palpitation, dyspnea, and chest pain. The physical examination, and laboratory and radiological findings are not specific, making the diagnosis difficult, which requires an elevated clinical suspicion.The most accurate noninvasive diagnostic method is indium-111 antimyosin myocardial scintigraphy 4 . This technique is not available in our country. However, another technique of nuclear medicine that uses gallium 67, a marker of inflammation, has been used despite its lower sensitivity and specificity.The endomyocardial biopsy, using Dallas histopathologic criteria, has been the standard diagnostic method, despite its low sensitivity. That technique has been boosted...

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Immunomodulation of Autoimmune and Inflammatory Diseases with Intravenous Immune Globulin

Cited by 1,110 publications

References 84 publications

Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome: randomised trial

Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome: randomised trial

Vitiligo y terapia con inmunoglobulina intravenosa: a propósito de un paciente con síndrome de Sjögren

Insuficiência renal aguda após uso de imunoglobulina intravenosa para tratamento de miocardite

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