Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 780
Filtrar
Más filtros

Intervalo de año de publicación
1.
Rev Argent Microbiol ; 56(1): 25-32, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37704516

RESUMEN

In Argentina, hemolytic uremic syndrome (HUS) caused by EHEC has the highest incidence in the world. EHEC infection has an endemo-epidemic behavior, causing 20-30% of acute bloody diarrhea syndrome in children under 5 years old. In the period 2016-2020, 272 new cases per year were notified to the National Health Surveillance System. Multiple factors are responsible for HUS incidence in Argentina including person-to-person transmission. In order to detect possible EHEC carriers, we carried out a preliminary study of the frequency of kindergarten teachers with anti-LPS antibodies against the most prevalent EHEC serotypes in Argentina. We analyzed 61 kindergarten teachers from 26 institutions from José C. Paz district, located in the suburban area of Buenos Aires province, Argentina. Fifty-one percent of the plasma samples had antibodies against O157, O145, O121 and O103 LPS: 6.4% of the positive samples had IgM isotype (n=2), 61.3% IgG isotype (n=19) and 32.3% IgM and IgG (n=10). Given that antibodies against LPS antigens are usually short-lived specific IgM detection may indicate a recent infection. In addition, the high percentage of positive samples may indicate a frequent exposure to EHEC strains in the cohort studied, as well as the existence of a large non-symptomatic population of adults carrying pathogenic strains that could contribute to the endemic behavior through person-to-person transmission. The improvement of continuous educational programs in kindergarten institutions could be a mandatory measure to reduce HUS cases not only in Argentina but also globally.


Asunto(s)
Escherichia coli Enterohemorrágica , Infecciones por Escherichia coli , Síndrome Hemolítico-Urémico , Niño , Adulto , Humanos , Preescolar , Lipopolisacáridos , Infecciones por Escherichia coli/epidemiología , Diarrea/epidemiología , Síndrome Hemolítico-Urémico/epidemiología , Inmunoglobulina G , Inmunoglobulina M
2.
Actas Dermosifiliogr ; 115(1): 10-20, 2024 Jan.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37442420

RESUMEN

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.


Asunto(s)
Servicios de Planificación Familiar , Psoriasis , Humanos , Femenino , Embarazo , Adulto , Estudios Transversales , Calidad de Vida , Encuestas y Cuestionarios , Psoriasis/tratamiento farmacológico
3.
Actas Dermosifiliogr ; 115(1): T10-T20, 2024 Jan.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37923069

RESUMEN

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.


Asunto(s)
Servicios de Planificación Familiar , Psoriasis , Humanos , Femenino , Embarazo , Adulto , Estudios Transversales , Calidad de Vida , Encuestas y Cuestionarios , Psoriasis/tratamiento farmacológico
4.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37890582

RESUMEN

OBJECTIVE: Compare the proportions of use of biological therapy, surgeries, and hospitalizations between adults and pediatric inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC)-patients. PATIENTS AND METHODS: Observational, retrospective, and multicenter study. Data were collected from all consecutive IBD patients seen as outpatients or admitted to hospital, during 2015-2021, in two IBD tertiary centers in a South Brazilian capital. Patients with unclassified colitis diagnosis were excluded from this study. Patients were classified as having CD or UC and sub-categorized as adult or pediatric according to age. Data were analyzed using frequency, proportion, Fisher's exact test, and Chi-square test. RESULTS: A total of 829 patients were included: 509 with CD (378 adults/131 pediatric) and 320 with UC (225/95). Among patients with CD, no differences were observed for proportions of use of biological therapy (80.2% in pediatric vs. 73.3% in adults; P=0.129), surgery (46.6% vs. 50.8%; P=0.419), or hospitalization (64.9% vs. 56.9%; P=0.122). In UC, significant differences were observed for biological therapy (40.0% vs. 28.0%; P=0.048) and hospitalization (47.4% vs. 24.0%; P<0.001). No significant difference was observed in surgery rates (17.9% vs. 12.4%; P=0.219). CONCLUSIONS: Biological therapy and incidence of hospitalization were greater among pediatric patients with UC, compared with adults; no difference was observed in the need for abdominal surgery. In CD, no significant difference was observed in the three main outcomes between the age groups.

5.
Gac Med Mex ; 159(2): 154-160, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37094237

RESUMEN

Anti-cytokine autoantibodies (ACAA) have been reported to be an important cause of secondary immunodeficiencies. High titers of neutralizing autoantibodies may cause susceptibility to different life-threatening infectious diseases. For example, neutralizing autoantibodies against IFNg have been reported to be correlated with susceptibility to mycobacterial infections and intracellular fungal pathogens. Autoantibodies against IL-6 were detected in patients with subcutaneous abscesses and recurrent staphylococcal cellulitis; on the other hand, patients with cryptococcosis, nocardiosis, and pulmonary alveolar proteinosis were positive for autoantibodies to GM-CSF. A relationship has also been established between autoantibodies against IL-17 and IL-22 and chronic mucosal Candida infections, which have been identified in patients with APECED or thymoma. Autoantibodies against type-I IFN have been recently reported during the onset of acute COVID-19. These ACAAs resemble genetic defects in cytokines or their signaling pathways. Therefore, they may be considered to be primary immunodeficiencies phenocopies. Consequently, the detection of ACAA could be important in the diagnosis of patients, particularly in the case of late-onset diseases, in order to decide appropriate treatments. This review presents an overview of current understanding of ACAA-associated secondary immunodeficiencies.


Los autoanticuerpos anticitocinas (ACAA) han sido reportados como causa importante de inmunodeficiencias secundarias. Altos títulos de autoanticuerpos neutralizantes pueden causar susceptibilidad a diferentes enfermedades infecciosas potencialmente mortales. Por ejemplo, se ha informado que autoanticuerpos neutralizantes contra IFNg se correlacionan con susceptibilidad a infecciones micobacterianas y patógenos fúngicos intracelulares. Autoanticuerpos contra IL-6 se detectaron en pacientes con abscesos subcutáneos y celulitis estafilocócica recurrente; asimismo, pacientes con criptococosis, nocardiosis y proteinosis alveolar pulmonar fueron positivos a autoanticuerpos contra GM-CSF. También se ha establecido una relación entre los autoanticuerpos contra IL-17 e IL-22 y las infecciones crónicas por Candida en mucosas, que se han identificado en pacientes con poliendocrinopatía autoinmune tipo 1 o timoma. Recientemente se han reportado autoanticuerpos contra interferón tipo I durante el inicio de COVID-19 aguda. Estos ACAA se asemejan a defectos genéticos en citocinas o en sus rutas de señalización. Por ello, pueden considerarse fenocopias de inmunodeficiencias primarias. De esta forma, la detección de ACAA podría ser importante en el diagnóstico, particularmente en pacientes con enfermedades de aparición tardía, para decidir los tratamientos apropiados. Esta revisión presenta una descripción general de la comprensión actual de las inmunodeficiencias secundarias asociadas a ACAA.


Asunto(s)
COVID-19 , Criptococosis , Síndromes de Inmunodeficiencia , Humanos , Citocinas , Autoanticuerpos
6.
Gac Med Mex ; 159(1): 55-64, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36930561

RESUMEN

INTRODUCTION: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). OBJECTIVE: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. METHODS: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. RESULTS: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complements C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. CONCLUSIONS: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.


INTRODUCCIÓN: Los anticuerpos anti-Ro52/TRIM21 son marcadores de varias enfermedades reumáticas autoinmunes sistémicas (ERAS). OBJETIVO: Evaluar si los anticuerpos anti-Ro52/TRIM21 están relacionados con anomalías en los circuitos inflamatorios. MÉTODOS: Estudio transversal de pacientes consecutivos y ambulatorios con ERAS. Los anticuerpos anti-Ro52/TRIM21 y la proteína amiloide sérica se midieron mediante ELISA; los paneles para 18 citocinas y nueve quimiocinas se analizaron en una plataforma de lectura Luminex; la proteína C reactiva (hs-CRP) y el complemento se midieron mediante nefelometría. RESULTADOS: Se incluyeron 167 pacientes, 143 con lupus eritematoso sistémico (LES), 16 con síndrome de Sjögren primario y ocho con esclerosis sistémica; 41 fueron positivos para anticuerpos anti-Ro52/TRIM21 (24 %). Los pacientes con anticuerpos anti-Ro52/TRIM21 tuvieron niveles séricos más altos de IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP y quimiocinas CCL4, CXCL8, CXCL10 y CXCL12; y más bajos de complemento C4. Los títulos de anticuerpos anti-Ro52/TRIM21 correlacionaron positivamente con IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10 y hs-CRP; y negativamente con complemento C3 y C4. Al incluir solo LES, no se identificó asociación entre los anticuerpos anti-Ro52/TRIM21 y la actividad de la enfermedad o la afectación específica de órganos. CONCLUSIONES: Los anticuerpos anti-Ro52/TRIM21 se asocian a circuitos aberrantes de citocinas y niveles elevados de moléculas angiogénicas y quimioatrayentes de neutrófilos y monocitos, lo que sugiere un papel activo de esos anticuerpos en las ERAS.


Asunto(s)
Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Síndrome de Sjögren , Humanos , Proteína C-Reactiva , Estudios Transversales , Interleucina-2 , Interleucina-4 , Interleucina-6 , Citocinas , Autoanticuerpos
7.
Gac Med Mex ; 159(4): 287-295, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37699227

RESUMEN

BACKGROUND: Vaccination is the most effective intervention for reducing the burden of SARS-CoV-2-related disease; however, gaps in knowledge regarding cancer patients (CPs) immune response persist. OBJECTIVES: To evaluate the humoral response (anti-S antibodies) in CPs and healthcare workers (HCWs) vaccinated with two doses of BNT162b2 or AZD122 vaccines. MATERIAL AND METHODS: Polyspecific anti-SARS-CoV-2 spike protein (anti-S) antibodies were quantified, and a 1:1 propensity score was used to balance baseline characteristics. Multiple logistic regressions were carried out to evaluate the effect of humoral response-related variables. RESULTS: One-hundred and twenty-seven CPs (22%) and 439 HCWs (78%) were included. Both populations developed anti-S antibodies in response to vaccination. The mRNA-based vaccine (BNT162b2) was associated with higher odds of having anti-S antibody titers ≥ 1,000 U/mL, while active cancer was related to a lower probability of developing high antibody titers. CONCLUSIONS: The BNT162b2 vaccine was associated with a higher humoral response. It is necessary for more information and vaccination strategies to be available for immunosuppressed patients in order to select the best biologics for this population based on individual characteristics.


ANTECEDENTES: La vacunación es la intervención más efectiva para reducir la carga de enfermedad por SARS-CoV-2; sin embargo, persisten brechas en el conocimiento en relación con la respuesta inmunológica de los pacientes con cáncer (PC). OBJETIVOS: Evaluar la respuesta humoral (anticuerpos anti-S) en PC y trabajadores de salud (TS) vacunados con dos dosis de la vacuna BNT162b2 o AZD122. MATERIAL Y MÉTODOS: Se cuantificaron anticuerpos poliespecíficos contra la proteína de espiga de SARS-CoV-2 (anti-S) y se efectuó una puntuación de propensión 1:1 para equilibrar las características basales. Se realizaron regresiones logísticas múltiples para evaluar el efecto de las variables relacionadas con la respuesta humoral. RESULTADOS: Se incluyeron 127 PC (22 %) y 439 TS (78 %). Ambas poblaciones desarrollaron anticuerpos anti-S en respuesta a la vacunación. La vacuna de ARNm (BNT162b2) se asoció a mayor probabilidad de mostrar concentraciones de anticuerpos anti-S ≥ 1000 UI/mL, mientras que el cáncer activo se relacionó con menor probabilidad de presentar títulos altos de anticuerpos. CONCLUSIONES: La vacuna BNT162b2 se asoció a respuesta humoral mayor. Es necesario contar con más información y estrategias de vacunación en pacientes inmunosuprimidos. Es relevante la selección de los mejores biológicos para esta población y considerar las características individuales.


Asunto(s)
COVID-19 , Neoplasias , Humanos , Prevalencia , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Personal de Salud
8.
Actas Dermosifiliogr ; 114(2): 125-131, 2023 Feb.
Artículo en Inglés, Español | MEDLINE | ID: mdl-36115385

RESUMEN

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen. In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments.


Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína , Vasculitis Leucocitoclástica Cutánea , Vasculitis , Humanos , Piel/patología , Trastornos Relacionados con Cocaína/complicaciones , Trastornos Relacionados con Cocaína/diagnóstico , Trastornos Relacionados con Cocaína/patología , Vasculitis Leucocitoclástica Cutánea/complicaciones , Vasculitis Leucocitoclástica Cutánea/patología , Cocaína/efectos adversos , Levamisol/efectos adversos , Anticuerpos Anticitoplasma de Neutrófilos
9.
Gac Med Mex ; 158(3): 141-149, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35894744

RESUMEN

Complement regulatory proteins (mCRPs) CD55, CD46 and CD59 have been proposed as key elements in therapeutic resistance against cancer. mCRP-expressing tumor cells, in addition to hindering trastuzumab, pertuzumab and sacituzumab-govitecan therapeutic activity in breast cancer, can regulate biological processes that promote tumor progression. This review describes the structure of mCRPs and analyzes their expression using transcriptomic databases from breast cancer patients, in addition to collecting information on mCRPs interactions and signaling in tumor cells. Given that mCRPs are relevant targets, several strategies that have been explored for their inhibition and regulation in order to increase therapeutic efficacy and prevent cancer resistance and progression are described.


Se ha propuesto a las proteínas reguladoras de complemento (mCRP) CD55, CD46 y CD59 como piezas clave en la resistencia terapéutica contra el cáncer. Las células tumorales que expresan las mCRP, además de obstaculizar la actividad terapéutica de trastuzumab, pertuzumab y sacituzumab-govitecan en cáncer de mama, pueden regular procesos biológicos que promueven la progresión tumoral. Esta revisión describe la estructura de las mCRP y analiza su expresión a partir de bases de datos transcriptómicos de pacientes con cáncer de mama; también recopila información de interacciones y señalización de las mCRP en células tumorales. Dado que estas mCRP son dianas relevantes, se describen diversas estrategias para su inhibición y regulación para incrementar la eficacia terapéutica y evitar la resistencia y progresión del cáncer.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Antígenos CD55/metabolismo , Activación de Complemento , Proteínas del Sistema Complemento/fisiología , Femenino , Humanos , Proteína Cofactora de Membrana/metabolismo , Trastuzumab
10.
Gastroenterol Hepatol ; 43(1): 34-45, 2020 Jan.
Artículo en Inglés, Español | MEDLINE | ID: mdl-31810796

RESUMEN

Despite unique immunoregulatory properties pointing toward tolerance, the liver allograft can be negatively impacted by humoral alloreactivity, with immediate as well as long-term harmful consequences. With regard to the unmet need of long-term outcomes improvement after liver transplantation, donor-specific antibodies have recently been the matter of intense study in this context. We review here recent advances regarding the understanding of the impact of preformed as well as de novo anti-human leukocyte antigen donor-specific antibodies in liver transplantation and discuss potential strategies to overcome this problem.


Asunto(s)
Aloinjertos/inmunología , Anticuerpos/inmunología , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Trasplante de Hígado/efectos adversos , Donantes de Tejidos , Anticuerpos/análisis , Humanos , Terapia de Inmunosupresión , Inmunología del Trasplante
11.
Gastroenterol Hepatol ; 43(9): 526-536, 2020 Nov.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32921478

RESUMEN

OBJECTIVE: To evaluate the performance of the quantitative markers of hepatitis B core-related antigen (HBcrAg) and anti-hepatitis B core antigen antibodies HbcAb versus hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA) in predicting liver fibrosis levels in chronic hepatitis B patients. METHODS: Two hundred and fifty hepatitis B e antigen (HBeAg)-positive and 245 HBeAg-negative patients were enrolled. With reference to the Scheuer standard, stage 2 or higher and stage 4 liver disease were defined as significant fibrosis and cirrhosis, respectively. A receiver operating characteristic (ROC) curve was used to evaluate the performance of the HBV markers investigated. RESULTS: The areas under the ROC curves (AUCs) of HBcrAg in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.577 and 0.700) were both close to those of HBsAg (0.617 and 0.762) (both P> 0.05). In HBeAg-negative patients (0.797 and 0.837), they were both significantly greater than those of HBV DNA (0.723 and 0.738) (P=0.0090 and P=0.0079). The AUCs of HBcAb in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.640 and 0.665) were both close to those of HBsAg. In HBeAg-negative patients (0.570 and 0.621), they were both significantly less than those of HBcrAg (P <0.0001 and P=0.0001). Specificity in predicting significant fibrosis and sensitivity in predicting cirrhosis in HBeAg-positive patients, using a single cut-off of HBsAg ≤5,000 IU/ml, were 76.5% and 72.7%, respectively. In HBeAg-negative patients, using a single cut-off of HBcrAg>80kU/ml, they were 85.9% and 81.3%, respectively. CONCLUSIONS: HBsAg has good performance in predicting liver fibrosis levels in HBeAg-positive and HBeAg-negative patients, and HBcrAg has very good performance in predicting liver fibrosis levels in HBeAg-negative patients.


Asunto(s)
ADN Viral/sangre , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Biomarcadores/sangre , Humanos , Valor Predictivo de las Pruebas
12.
Gac Med Mex ; 156(3): 228-235, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32538994

RESUMEN

Therapeutic antibodies are recombinant proteins used in the treatment of cancer. There is a new generation of monoclonal antibodies with activity against cancer cells, known as antibody-drug conjugates. These molecules are made up of three elements: a monoclonal antibody, a highly potent cytotoxic drug, and a chemical linker that binds them together. The antibody recognizes tumor antigens, thereby allowing targeted delivery of the cytotoxic agent to cancer cells. After recognizing its antigen, the antibody-drug conjugate is endocytosed by the target cells, where the protein fraction is degraded into lysosomes, releasing the cytotoxic drug. This article reviews antibody-drug conjugates general characteristics and describes the clinical evidence of efficacy and safety of the first four approved by regulatory agencies in the United States and Europe.


Los anticuerpos terapéuticos son proteínas recombinantes empleadas en el tratamiento del cáncer. Existe una nueva ­generación de anticuerpos monoclonales con actividad contra las células cancerosas, conocidos como anticuerpos conjugados a fármacos. Estas moléculas están integradas por tres elementos: un anticuerpo monoclonal, un fármaco citotóxico con alta potencia y un enlazador químico que los une. El anticuerpo reconoce antígenos tumorales, por lo que permite la entrega dirigida del agente citotóxico hacia las células cancerosas. Tras el reconocimiento de su antígeno, el anticuerpo conjugado a fármaco es endocitado por las células blanco, donde se induce la degradación lisosomal de la fracción proteica y se libera el fármaco citotóxico. En el presente artículo se revisan las características generales de los anticuerpos conjugados a fármacos y se describe la evidencia clínica de la eficacia y seguridad de los primeros cuatro aprobados por las agencias reguladoras de Estados Unidos y Europa.


Asunto(s)
Antineoplásicos/administración & dosificación , Inmunoconjugados/administración & dosificación , Neoplasias/tratamiento farmacológico , Antígenos de Neoplasias/inmunología , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Biotecnología , Humanos , Inmunoconjugados/efectos adversos , Inmunoconjugados/farmacología , Neoplasias/inmunología
13.
Actas Dermosifiliogr ; 108(8): 721-728, 2017 Oct.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28388991

RESUMEN

Metastatic or locally advanced unresectable melanoma carries a high morbidity and mortality. However, notable advances have been made in recent years in the systemic treatment of this disease, with the appearance of targeted therapy using tyrosine kinase inhibitors that block the mitogen activated protein kinase pathway, and of modern immunotherapy with immune-modulating monoclonal antibodies. In this paper, we provide an update of available data on new immune therapies and we review the clinical development that led to their approval for use in routine clinical practice.


Asunto(s)
Inmunoterapia/métodos , Melanoma/terapia , Terapia Molecular Dirigida/métodos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antígenos de Neoplasias/inmunología , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Ensayos Clínicos como Asunto , Predicción , Humanos , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Melanoma/inmunología , Melanoma/secundario , Proteínas de Neoplasias/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Terapia Recuperativa , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Escape del Tumor/efectos de los fármacos , Escape del Tumor/inmunología
14.
Actas Dermosifiliogr ; 108(10): 902-910, 2017 Dec.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28801011

RESUMEN

Paraneoplastic pemphigus (PNP), a subset of pemphigus, is a unique autoimmune blistering condition that can affect multiple organs other than the skin. It is a life-threatening disease associated with an underlying malignancy, most commonly of lymphoproliferative origin. The clinical picture may resemble pemphigus, pemphigoid, erythema multiforme, graft-versus-host disease, or lichen planus. The earliest and most consistent finding is a painful, severe, chronic and often recalcitrant stomatitis. Treatment of PNP is difficult. Immunosuppressive agents are required to decrease blistering, and treating the underlying tumor may control autoantibody production. In this review, we included essential diagnostic aspects of PNP and the most useful treatment options in the dermatologist practice.


Asunto(s)
Síndromes Paraneoplásicos/etiología , Pénfigo/etiología , Antígenos de Neoplasias/inmunología , Autoanticuerpos/biosíntesis , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Bronquiolitis Obliterante/etiología , Enfermedad de Castleman/complicaciones , Enfermedad de Castleman/inmunología , Diagnóstico Diferencial , Humanos , Inmunidad Celular , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/tratamiento farmacológico , Síndromes Paraneoplásicos/epidemiología , Pénfigo/diagnóstico , Pénfigo/tratamiento farmacológico , Pénfigo/epidemiología , Pronóstico , Rituximab/uso terapéutico , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Estomatitis/diagnóstico , Estomatitis/tratamiento farmacológico , Estomatitis/etiología
15.
Actas Dermosifiliogr ; 108(5): 445-456, 2017 Jun.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28267955

RESUMEN

BACKGROUND: The induction of antinuclear antibodies (ANA) and the onset of autoimmune diseases have been reported after treatment with tumor necrosis factor (TNF) inhibitors, though controversy persists. OBJECTIVES: To determine the frequency of onset of autoimmune diseases and of the appearance of autoantibodies in psoriasis patients administered TNF inhibitors (adalimumab and etanercept) subcutaneously and to correlate this with the effectiveness of treatment, adverse effects, and the order of use of TNF inhibitors. We also tried to identify any factors that might predict the appearance of ANA and autimmune diseases. METHODS: We performed a retrospective study of a cohort of 121 patients monitored over an 11-year period. ANA were measured at baseline and at 3, 6, and 12 months; positive results were followed up by study of antibodies to double-stranded DNA. Extractable nuclear antigen (ENA) antibodies were also studied at baseline and at 3, 6, and 12 months. Patients with a baseline assay of ANA and ENA at least one more assay during the first year were included in the study, and these antibodies were measured annually thereafter. Psoriasis area severity index was calculated and adverse effects were recorded at each visit. RESULTS: A significant increase in ANA positivity was observed during treatment of moderate-to-severe psoriasis with adalimumab and etanercept, but this was not associated with the onset of autoimmune diseases. No correlation was observed with treatment efficacy, the order of use of TNF inhibitors, or the appearance of adverse effects. No predictive factors for the appearance of ANA were identified, except for the body mass index. CONCLUSIONS: We recommend ANA measurement and screening for autoimmune diseases prior to treatment with TNF inhibitors, but not routine serial measurements of ANA during follow-up except in patients with signs or symptoms suggestive of autoimmune disease.


Asunto(s)
Adalimumab/efectos adversos , Anticuerpos Antinucleares/biosíntesis , Antirreumáticos/efectos adversos , Enfermedades Autoinmunes/inducido químicamente , Etanercept/efectos adversos , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Adolescente , Adulto , Anciano , Anticuerpos Antinucleares/sangre , Antígenos Nucleares/inmunología , Antirreumáticos/uso terapéutico , Autoantígenos/inmunología , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/tratamiento farmacológico , ADN/inmunología , Etanercept/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
17.
Trop Med Int Health ; 21(5): 687-90, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26847641

RESUMEN

OBJECTIVE: The emergence of West Nile virus (WNV) in several European countries increases the risk of its introduction to Germany. This study evaluated a new method for WNV surveillance by testing for maternal antibodies in chicken eggs. METHODS: A total of 1,990 eggs were collected in 35 sampling sites in the south-west of Germany and tested for WNV-specific antibodies. RESULTS: The results did not indicate evidence for WNV circulation in the study area. CONCLUSION: This work serves as a proof-of-concept that such a method is useful and a potential alternative to use of sentinel chicken for regular WNV surveillance.


Asunto(s)
Anticuerpos Antivirales/aislamiento & purificación , Huevos/virología , Vigilancia de Guardia , Virus del Nilo Occidental/inmunología , Animales , Pollos/inmunología , Pollos/virología , Ensayo de Inmunoadsorción Enzimática , Femenino , Alemania
18.
Trop Med Int Health ; 21(12): 1545-1551, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27699992

RESUMEN

OBJECTIVE: Autoantibodies cross-reacting with the ß1 adrenergic receptor (anti-ß1AR and anti-p2ß) and cardiac myosin antigens (anti-B13) have been related to the pathogenesis of chronic Chagas heart disease (CCHD). Studies exploring their levels in different stages are scarce. We aimed to evaluate the relationship of these autoantibodies with the clinical profile of chronic patients, especially regarding their classificatory accuracy in severe presentation with heart failure. METHODS AND RESULTS: We conducted a cross-sectional study of 155 T. cruzi-seropositive patients and 26 age- and gender-matched healthy controls. They were categorised in three stages of CCHD. Serum antibodies were measured by specific immunoassays. Symptomatic individuals showed increased levels of anti-ß1AR and anti-B13, while anti-p2ß antibodies were similar between groups. A composite logistic regression model including anti-B13, anti-ß1AR antibody levels and age was able to predict systolic heart failure yielding an area under the curve of 83% (sensitivity of 67% and specificity of 89%). CONCLUSIONS: In our study, anti-ß1AR and anti-B13 antibodies were higher in individuals with chronic Chagas heart disease stage III, mainly in those with dilated cardiomyopathy associated with systolic heart failure. Logistic regression analysis showed that both antibodies were good predictors of severe CCHD. As well as being involved in disease progression, anti-ß1AR and anti-B13 antibodies may be used as a serum marker of poor prognosis in terms of heart compromise.


Asunto(s)
Autoanticuerpos/sangre , Miosinas Cardíacas/inmunología , Cardiomiopatía Chagásica/inmunología , Insuficiencia Cardíaca/etiología , Receptores Adrenérgicos beta 1/inmunología , Trypanosoma cruzi/inmunología , Adulto , Anciano , Área Bajo la Curva , Cardiomiopatía Chagásica/sangre , Cardiomiopatía Chagásica/parasitología , Enfermedad de Chagas , Estudios Transversales , Progresión de la Enfermedad , Femenino , Insuficiencia Cardíaca/inmunología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la Enfermedad
19.
Gastroenterol Hepatol ; 39(10): 656-662, 2016 Dec.
Artículo en Inglés, Español | MEDLINE | ID: mdl-27417563

RESUMEN

INTRODUCTION: The estimated seroprevalence of hepatitis C virus (HCV) in Spain is 1.7%, but is much higher in the at-risk population. The most efficient national screening strategy is unclear. AIMS: To estimate the prevalence of HCV among the at-risk population seen in primary care (PC), and to determine their epidemiological profile. MATERIALS AND METHODS: Cross-sectional descriptive prevalence study that included adult patients with risk factors for HCV infection seen in PC in the southwest Madrid region between 2010 and 2012. RESULTS: A total of 158 patients (men=51.3%), mean age 46 years (SD=16.6), were included. The most common risk factors were hypertransaminasaemia (44.3%) and major surgery (13.3%). Immigration, unsafe sexual practices, and tattoos or body piercing were more prevalent in patients younger than 45 years of age. Fifteen patients (9.5%) were positive for anti-HCV; 9 of these (5.7%) were HCV-ARN positive. Of the positive patients, 4 (44.4%) had significant fibrosis at diagnosis (F3-F4). Male patients had a higher rate of positive anti-HCV results (13.8 vs. 5.3%; P=.072), as did patients older than 45 years of age (12.8 vs. 6.3%; P=.167). Intravenous and intranasal drug use were associated with a higher rate of positive anti-HCV results (50 vs. 8.5%; P=.005 and 66.7 vs. 8.4%; P=.001, respectively). CONCLUSIONS: Patients with risk factors for HCV infection have high seroprevalence. Screening programmes must therefore be implemented to detect HCV infection in this population in PC.


Asunto(s)
Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Adulto , Anciano , Comorbilidad , Estudios Transversales , Femenino , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Atención Primaria de Salud , ARN Viral/sangre , Factores de Riesgo , Asunción de Riesgos , Estudios Seroepidemiológicos , España/epidemiología , Población Urbana , Viremia/epidemiología
20.
Rev Chil Pediatr ; 87(6): 487-493, 2016.
Artículo en Español | MEDLINE | ID: mdl-27476614

RESUMEN

INTRODUCTION: Subacute anti-NMDA receptor encephalitis was recognised in 2007 as a clinical entity, and was first described in young women with ovarian teratoma. The first paediatric series unrelated with tumours was reported in 2009. OBJECTIVE: To present the clinical features, treatment, and prognosis of 13 patients with anti-NMDA receptor encephalitis in Chile. PATIENTS AND METHOD: A description is presented of 13 children, 9 males, aged between 1 and 16 years, diagnosed between 2009 and 2016 in 7 hospitals. All patients were evaluated with cerebral magnetic resonance and electroencephalogram. Cytochemical, oligoclonal bands and virus studies (PCR and antibodies) were performed in cerebrospinal fluid. All patients were evaluated in search of anti NMDA receptor in serum and cerebrospinal fluid. Tumor imaging studies were performed in all children. RESULTS: All children began the disease with psychiatric symptoms, and 11/13 had seizures. All of them subsequently presented with psychomotor agitation, dystonia, and bucolingual dyskinesias, with 11/13 loss of language and 6/13 autonomic disorders. All of them (13/13) had positive anti-NMDA receptor antibodies. CSF was normal in 12/13 children, positive oligoclonal bands in 6/10 patients, normal brain resonance in 13/13 children, EEG changes in 11/13 children, and abnormal SPECT in 6/6 children. A methylprednisolone bolus of 30mg/kg was given for 3-5 days to 12/13 children, and 6 received immunoglobulin 2g/kg. The large majority (12/13) of children recovered 1-4 months after disease onset. One child had a recurrence one year later, and recovered quickly. CONCLUSIONS: Subacute encephalitis due to NMDA anti-receptor antibodies should be suspected in children with psychiatric disorders and abnormal movements. Functional studies, such as EEG and SPECT are valuable diagnostic support. Early detection of this encephalitis leads to a faster recovery of patients.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Electroencefalografía , Imagen por Resonancia Magnética/métodos , Convulsiones/etiología , Adolescente , Encefalitis Antirreceptor N-Metil-D-Aspartato/fisiopatología , Niño , Preescolar , Chile , Femenino , Humanos , Inmunoglobulinas/uso terapéutico , Lactante , Masculino , Metilprednisolona/uso terapéutico , Pronóstico , Recurrencia , Convulsiones/epidemiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA