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Factores clínicos de riesgo para el desarrollo de la vitreorretinopatía proliferante (VRP) postquirúrgica: Estudio prospectivo Clinical risk factors for postoperative proliferative vitreoretinopathy (PVR): A prospective study  [cached]
E Rodríguez de la Rúa,V Martínez,J Aragón,RM Sanabria
Archivos de la Sociedad Espa?ola de Oftalmología , 2003,
Abstract: Objetivo: Identificar los factores de riesgo de VRP, la incidencia y el momento de aparición de esta complicación en una serie prospectiva de desprendimientos de retina regmatógenos (DR). Métodos: Se ha realizado un estudio multicéntrico y prospectivo de 223 casos de DR. Se han incluido 83 variables referentes a características preoperatorias, intraoperatorias y postquirúrgicas. Se ha efectuado un análisis de regresión logística. Resultados: De los 223 casos de DR, 22 desarrollaron una VRP (incidencia 9,9%, intervalo de confianza al 95%: 5,9-13,9). Se han detectado 4 factores con una odds-ratio superior a 1,0 (la existencia de un DR de 4 cuadrantes, el empleo de crioterapia, la afaquia o pseudofaquia y la necesidad de utilizar cerclaje). Ninguno de estos factores ha presentado una p<0,05. El 77,2% de los VrP aparecieron en el primer mes tras la cirugía. Conclusiones: Este estudio ha permitido establecer la incidencia de la VRP, y su tiempo de aparición, aunque no ha resultado efectivo para establecer asociaciones positivas con los factores de riesgo. Purpose: To identify clinical risk factors for development of postoperative PVR, to determine the incidence of this complication and its time of onset by a prospective multicentric study. Methods: A multicentric and prospective study of 223 patients with rhegmatogenous retinal detachment (RD) was conducted. Logistic regression analysis was used to identify risk factors for PVR among 83 variables related to preoperative, intraoperative and postoperative characteristics. Results: 22 out of 223 RD developed PVR (incidence 9.9%, confidence interval 95%: 5.9-13.9). After logistic regression analysis, four variables showed an odds ratio higher than 1.0 (RD affecting 4 quadrants, cryopexy, aphakia/pseudophakia and those RD in which an encircling band was implanted). None of these factors showed a p value lower than 0.05. Most of postoperative PVR (77.2%) appeared in the first month after surgery. Conclusions: This study establishes the incidence of PVR, and its time of onset, but it was not effective to identify clinical risk factors with a high level of confidence.
Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor
Alejandro Balsa, Arancha Cabezón, Gisela Orozco, Tatiana Cobo, Eugenia Miranda-Carus, Miguel ángel López-Nevot, José Luis Vicario, Emilio Martín-Mola, Javier Martín, Dora Pascual-Salcedo
Arthritis Research & Therapy , 2010, DOI: 10.1186/ar2975
Abstract: We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined.We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found.HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.Rheumatoid arthritis (RA) is a complex autoimmune disease that develops from the combined effects of genetic and environmental factors. It is estimated that the heritability of RA accounts for about 50% to 60%, and the most important genetic risk factors are the HLA class II molecules, which contribute to one third of the total genetic susceptibility [1,2]. There is extensive evidence for the association between certain HLA-DRB1 alleles with a conserved amino acid sequence (Q/RK/RRAA) at residues 70 to 74 in the third hypervariable region of the DRβ1 chain, the so-called shared epitope (SE), and susceptibility to and severity of RA [3,4].Autoimmunity in RA is characterized by the presence of autoantibodies. Rheumatoid factor (RF) is not specific to RA as it may be present in other diseases and in healthy older individuals [5]. In contrast, anti-citrullinated protein antibodies (ACPAs) seem to play a pivotal role in the pathogene
Journal of Research in Medical Sciences , 2001,
Abstract: Introduction: Leishmania recidivans, also known as Lupoid Leishmaniasis is one of the uncommon clinical picture of cutaneous Leishmaniasis occurs in 5-7 percent of patients. In this clinical picture the lesions reactivate after a few months or years. The reason for reactivation is not clear, yet. The most popular hypothesis is the impairment of cell mediated immunity. It may be relate on HLA antigens of the patients. Methods: We selected 30 Lupoid Leishmaniasis patients (18 females and 12 males, aged between 4 to 70 years old). One hundred healthy peoples were matched to patients according to standardized criteria. Results: HLA A3, A11, A24 and A30 were more frequent in patients (P < 0.05). Discussion: Our study demonstrate a significant association between Lipoid Leishmaniasis and HLA antigen.
El Fibrinógeno: Factor de Riesgo Cardiovascular
Espinosa,Raúl A;
Investigación Clínica , 2002,
Abstract: this paper demonstrate that plasmatic fibrinogen is a risk factor for ischaemic cardiovascular disease. apart from its hemostatic functions, it has an important role in the atherothrombotic process. prospective studies in a normal population and on patients with pre-existent cardiovascular disease demonstrate that fibrinogen is a predictor of cardiovascular events, either as first episode or recurrence. it is also reviewed a epidemiological study which is been carried out in venezuela as a pilot study for latinamerica because our population is different from those where the studies have been performed up to now. it is also mentioned the factors that influence the fibrinogen levels, some of them can be modified which could be useful for the prevention of the disease. it is considered the necessity of further studies to evaluate the benefit of the control of the fibrinogen level.
Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity  [PDF]
Stephanie Ascough,Rebecca J. Ingram,Karen K. Chu,Catherine J. Reynolds,Julie A. Musson,Mehmet Doganay,G?khan Metan,Yusuf Ozkul,Les Baillie,Shiranee Sriskandan,Stephen J. Moore,Theresa B. Gallagher,Hugh Dyson,E. Diane Williamson,John H. Robinson,Bernard Maillere,Rosemary J. Boyton,Daniel M. Altmann
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004085
Abstract: Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.
HLA-DRB1 as a risk factor in children with autoimmune hepatitis and its relation to hepatitis A infection
Amel AM Elfaramawy, Reham M Elhossiny, Amal A Abbas, Heba Aziz
Italian Journal of Pediatrics , 2010, DOI: 10.1186/1824-7288-36-73
Abstract: 25 children with AIH were subjected to HLA-DRB 1 typing performed by sequence specific oligonucleotide probe technique and compared to HLA-DRB1 found in 548 normal populations.The most frequent alleles found in our children with AIH were HLA-DRB1*13 (36%), HLA-DRB1*04 (18%) and HLA-DRB1*03 (14%). HLA-DRB1*13 was significantly more frequent in AIH patients compared to controls. In type I AIH patients HLA-DRB1*13 was the most frequent allele (32.4%), followed by HLA-DRB1*04 in (20.6%) and HLA-DRB1*03 in (14.7%), While in type II, the most frequent alleles were HLA-DRB1*13 in (40%), HLA-DRB1*07 (20%) and HLA-DRB1*15 in (20%). HLA-DRB1*12 was significantly more frequent in AIH patients with positive Hepatitis A IgM than in patients with negative hepatitis A IgM. No statistically significant difference between partial responders and complete responders to treatment as regards HLA-DRB1 subtypes.It is concluded from the previous study that HLA-DRB1*13 may be a susceptibility allele for the occurrence of autoimmune hepatitis in our population. HLA-DRB1*07 and HLA-DRB1*15 may be susceptibility alleles for occurrence of autoimmune hepatitis type 2. HLA-DRB1*12 association with AIH in patients triggered by hepatitis A needs further studies.Auto-immune hepatitis (AIH) is a chronic liver disorder of unknown cause that leads to cirrhosis and liver failure when untreated. The disease usually affects females and is characterized by the presence of circulating auto antibodies and by severe interface hepatitis on liver biopsy [1].Two types of AIH have been proposed on the basis of serologic markers, type 1-AIH is the most common form worldwide while type 2-AIH occurs mainly in children and in Europe [2].Although the etiology of AIH is unknown, both genetic and environmental factors are involved in its expression [3]. Strong evidence suggests that defects in immunologic control of auto reactivity play a role in AIH pathogenesis [4].HLA antigens are the major determinants used by the b
HLA-E-Restricted Cross-Recognition of Allogeneic Endothelial Cells by CMV-Associated CD8 T Cells: A Potential Risk Factor following Transplantation  [PDF]
Mathilde Allard, Pierre Tonnerre, Steven Nedellec, Romain Oger, Alexis Morice, Yannick Guilloux, Elisabeth Houssaint, Béatrice Charreau, Nadine Gervois
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050951
Abstract: Although association between CMV infection and allograft rejection is well admitted, the precise mechanisms involved remain uncertain. Here, we report the characterization of an alloreactive HLA-E-restricted CD8 T cell population that was detected in the PBL of a kidney transplant patient after its CMV conversion. This monoclonal CD8 T cell population represents a sizable fraction in the blood (3% of PBL) and is characterized by an effector-memory phenotype and the expression of multiple NK receptors. Interestingly, these unconventional T cells display HLA-E-dependent reactivity against peptides derived from the leader sequences of both various HCMV-UL40 and allogeneic classical HLA-I molecules. Consequently, while HLA-E-restricted CD8 T cells have potential to contribute to the control of CMV infection in vivo, they may also directly mediate graft rejection through recognition of peptides derived from allogeneic HLA-I molecules on graft cells. Therefore, as HLA-E expression in nonlymphoid organs is mainly restricted to endothelial cells, we investigated the reactivity of this HLA-E-restricted T cell population towards allogeneic endothelial cells. We clearly demonstrated that CMV-associated HLA-E-restricted T cells efficiently recognized and killed allogeneic endothelial cells in vitro. Moreover, our data indicate that this alloreactivity is tightly regulated by NK receptors, especially by inhibitory KIR2DL2 that strongly prevents TCR-induced activation through recognition of HLA-C molecules. Hence, a better evaluation of the role of CMV-associated HLA-E-restricted T cells in transplantation and of the impact of HLA-genotype, especially HLA-C, on their alloreactivity may determine whether they indeed represent a risk factor following organ transplantation.
Limited Promiscuity of HLA-DRB1 Presented Peptides Derived of Blood Coagulation Factor VIII  [PDF]
Simon D. van Haren, Aleksandra Wroblewska, Eszter Herczenik, Paul H. Kaijen, Aleksandra Ruminska, Anja ten Brinke, Alexander B. Meijer, Jan Voorberg
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080239
Abstract: The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4+ T cell-dependent process. Activation of FVIII-specific CD4+ T cells is dependent on the presentation of FVIII-derived peptides on MHC class II by antigen-presenting cells. Previously, we have shown that FVIII-pulsed human monocyte-derived dendritic cells can present peptides from several FVIII domains. In this study we show that FVIII peptides are presented on immature as well as mature dendritic cells. In immature dendritic cells half of the FVIII-loaded MHC class II molecules are retained within the cell, whereas in LPS-matured dendritic cells the majority of MHC class II/peptide complexes is present on the plasma membrane. Time-course studies revealed that presentation of FVIII-derived peptides was optimal between 12 and 24 hours after maturation but persisted for at least 96 hours. We also show that macrophages are able to internalize FVIII as efficiently as dendritic cells, however FVIII was presented on MHC class II with a lower efficiency and with different epitopes compared to dendritic cells. In total, 48 FVIII core-peptides were identified using a DCs derived of 8 different donors. Five HLA-promiscuous FVIII peptide regions were found – these were presented by at least 4 out of 8 donors. The remaining 42 peptide core regions in FVIII were presented by DCs derived from a single (30 peptides) or two to three donors (12 peptides). Overall, our findings show that a broad repertoire of FVIII peptides can be presented on HLA-DR.
Tabaquismo como factor de riesgo del infarto agudo al miocardio
Manrique Leal-Mateos,Teresita Solano- Chinchilla
Acta Médica Costarricense , 2006,
Abstract: Justificación: El tabaquismo es la principal causa de enfermedad, discapacidad y muerte prematura prevenible mundialmente; actualmente, es aceptado como un factor de riesgo para el desarrollo de enfermedades cardiovasculares. Sin embargo, aunque el tabaco es conocido como una causa directa de IAM, en el país es limitado el conocimiento de su fracción atribuible. Objetivo: Este estudio tiene como propósito evaluar el impacto que provoca el tabaquismo sobre los pacientes con IAM, por medio de su fracción atribuible. Así, pretende estimar la proporción de personas que podrían prevenir su desarrollo, si se evitara la exposición a este factor de riesgo. Métodos: Se realizó un estudio de casos y controles en los servicios de medicina interna y cirugía del Hospital San Juan de Dios, en el periodo comprendido entre el 1 de abril y el 23 de septiembre de 2005. Se definió como fumador aquel paciente que hubiera fumado al menos un cigarro por día, durante un a o. De acuerdo con el hábito de fumar, se clasificaron en: No fumadores (quienes nunca habían fumado), fumadores (quienes fumaran actualmente) y exfumadores. La magnitud de las asociaciones entre la exposición y el riesgo de la enfermedad se evaluó mediante la razón de probabilidades (Odds Ratio en inglés) para datos apareados 2:1, definiendo como no expuestos aquellos pacientes clasificados como no fumadores. Los exfumadores con más de 15 a os de haber abandonado el hábito fueron clasificados como no fumadores (dados los beneficios que representa esta situación a largo plazo) y aquellos con menos de 15 a os de haberlo abandonado, fumadores. Con el fin de medir el impacto del tabaquismo sobre los pacientes que padecen de infarto agudo al miocardio se utilizó el indicador de fracción atribuible. Para todo lo anterior se utilizó Epitable, del programa EpiInfo 6. Resultados: La Razón de Probabilidades para datos apareados 2:1 mostró una asociación positiva entre el fumado y del desarrollo de un IAM, de 2,58 (IC95% 1,17-5,70). La fracción atribuible en los expuestos fue del 64,7% (IC 95% 14,6-82,5). Discusión: Se puede concluir que un poco más de la mitad los casos que se diagnosticaron con IAM en el HSJD, durante el periodo de estudio obedecen a la exposición activa de los pacientes al tabaquismo. Rationale: Cigarrette smoking is the main, preventable cause of premature illness, disability and death worldwide. At present, is widely recognized as a risk factor for the development of cardiovascular disease. Nevertheless, even though tobacco is generaly accepted as a direct cause of acute myocardial infarction, in o
Análisis de la asociación de HLA DRB1-DQB1 y autoanticuerpos en familias con Síndrome Poliendocrino Autoinmune (APS) An analysis of the relationship between HLA DRB1-DQB1 and autoantibodies, in families with autoinmune polyendocrine syndrome (APS)
Silvia Botta,Silvana Roveto,P. Galarza,A. Perusco
Revista Argentina de Endocrinología y Metabolismo , 2008,
Abstract: El APS es la asociación de enfermedades endocrinas autoinmunes, con otros desórdenes autoinmunes no endocrinos, denominados componentes mayores y menores. Este síndrome se clasificó en 4 tipos. Las alteraciones de la respuesta inmune provocan fallas regulatorias de la misma; y polimorfismos de HLA, entre otros, sumado a factores adquiridos o permanentes, representan gatillos disparadores de la autoinmunidad. Nuestro objetivo fue buscar la asociación de HLA-DRB1*-DQB1* en individuos pertenecientes a dos familias, con diagnóstico en uno o más de ellos de APS, o con enfermedades autoinmunes aisladas. Determinar los anticuerpos séricos: a21-OH, aGAD y aTPO y observar la asociación con el haplotipo HLA. Estudiamos padres e hijos de dos familias, dos integrantes padecían APS tipo 2 y 3; y otros con enfermedades autoinmunes. Buscamos HLA-DRB1*-DQB1* y cuantificamos a21-OH, aTPO y aGAD. Los pacientes con APS 2 y 3 presentaron el HLA-DRB1*0301-DQB1*0201. De los individuos estudiados, 5/9 tenían este haplotipo HLA y al menos un autoanticuerpo positivo. Hallamos el factor genético en 2/3 de los integrantes con enfermedades autoinmunes correspondientes a componentes mayores. La relación observada, entre APS y HLA-DRB1*0301-DQB1*0201, aumenta la posibilidad de identificar personas en riesgo de contraer afecciones autoinmunes en grupos familiares, en los cuales algún integrante padece APS. The APS is the association of autoimmune endocrine diseases, with other non-endocrine autoimmune disorders, named mayor and minor components. This syndrome was classified in 4 types. The alterations of the immune response cause regulatory faults; and HLA polymorphisms, among others; taken in conjunction with acquired or permanent factors, these represent triggers of autoimmunity. Our objective was to find out the association of HLA-DRB1*-DQB1* in individuals belonging to two families, with diagnosis in at least one of them APS, or with isolated autoimmune diseases. To determine serum antibodies: a21-OH, aGAD and aTPO and to observe the association with HLA haplotype. We have studied parents and offspring of two families, two members who suffered APS type 2 and 3, and others with autoimmune diseases. We have looked for HLA-DRB1*-DQB1* and quantified a21-OH, aTPO and aGAD. Patients with APS 2 and 3 showed HLA-DRB1*0301-DQB1*0201. Among the population we have studied, 5/9 had this HLA haplotype and at least one positive auto antibody. We have found the genetic factor in 2/3 of the members with autoimmune diseases corresponding to greater components. The observed relation between APS a
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