Cracking the immune fingerprint of metal-organic frameworks.

The human body is in a never-ending chess game against pathogens. When the immune system, our natural defence tool, is weakened, these organisms are able to escape, overcoming the body's contingency plan, which results in the body going into a pathological state. To overcome this checkmate status, emerging nanomedicines have been successfully employed as one of the best tactics for boosting the immune response, manipulating the body's defence tools for the specific recognition/elimination of pathological cells via the active ingredient delivery. However, the vast majority of these drug-delivery systems (DDS) are considered to be exclusively passive vehicles, with nanoscale metal-organic frameworks (nanoMOFs) attracting a great deal of attention due to their versatility and ability to carry and deliver exceptional drug payloads and to modulate their biological bypass. Nonetheless, their intrinsic immunogenicity character has been never addressed. Considering the immense possibilities that nanoMOFs offer as a treatment platform, the present study aimed to unveil the immunological fingerprint of MOFs, including an in-deep evaluation of the cellular oxidation balance, the inflammation and recruitment of immune cells and the precise Th1/Th2 cytokine profile that is triggered. This study aims to gain insights that will make more feasible the design of customized immune-active MOF nanoplatforms according to targeted diseases, as the next ace up immune system sleeve.

Pronóstico global de los pacientes con isquemia crítica de las extremidades inferiores / Overall prognosis of patients with lower-limb critical ischaemia

Objetivo: Estudiar los factores que influyen en el pronóstico vital y funcional global de los pacientes con isquemia crítica de extremidades inferiores (IC), englobando cualquier sector afectado y modalidad de tratamiento. Material y métodos: Estudio de cohortes prospectivo en pacientes con IC. Se registraron: datos demográficos, factores de riesgo cardiovascular, comorbilidad, parámetros analíticos, cuestionario Mini Nutritional Assesment, tratamiento realizado y evolución. Se estudiaron las tasas de mortalidad, salvamento de extremidad y tiempo libre de reingreso y el impacto de los parámetros descritos sobre estas variables resultado mediante las curvas de Kaplan-Meier y la regresión de Cox. Resultados: Incluimos 133 pacientes, 103 (77,4%) hombres, con edad media de 74,8 años (DS 10,4; rango 52-93). En 97 casos (72,9%) presentaban lesiones tróficas. Se revascularizaron 87 pacientes (65,4%), 48 mediante técnicas abiertas y 39 endovasculares, 5 (3,8%) sufrieron una amputación mayor primaria, tratándose 41 (30,8%) de forma conservadora o mediante amputación menor. La supervivencia fue 85% y 81% a los 6 y 12 meses, con tasas de salvamento de extremidad de 84% y 82% y tiempo libre de reingreso de 52% y 31% para los mismos tiempos. La hipoalbuminemia aumentó el riesgo de mortalidad (p = 0,024) y una puntuación baja en el Mini Nutritional Assesment incrementó el riesgo de amputación mayor (p = 0,021). Hubo más reingresos en pacientes revascularizados mediante técnicas endovasculares (p = 0,001) y en los que presentaban lesiones tróficas (p = 0,001). Conclusiones: La malnutrición es un factor muy prevalente, potencialmente tratable, y determinante en el pronóstico, vital y funcional, de los pacientes con isquemia crítica de extremidades inferiores

Objetive: To study the factors that affect the vital and overall functional prognosis of patients with lower limb critical ischaemia (LLCI), including any diseased sector and treatment methods. Material and methods: A prospective cohort study was conducted on patients with LLCI. A record was made of their demographic data, cardiovascular risk factors, comorbidity, blood test parameters, Mini Nutritional Assessment (MNA) questionnaire, treatment, and outcome. An analysis was made on the mortality, limb salvage, and freedom from re-admission (FRR) rates, as well as the impact of the described parameters on these outcome variables, using Kaplan-Meier curves and Cox regression. Results: A total of 133 patients were included, 103 (77.4%) men, with a mean age of 74.8 years (SD 10.4; range 52-93). There was tissue loss in 97 (72.9%) cases. A total of 87 (65.4%) patients were revascularised, 48 using open techniques and 39 endovascular. A primary major amputation was performed on 5 (3.8%) patients, and 41 (30.8%) were treated conservatively, with or without minor amputation. Survival rates were 85% and 81% at 6 and 12 months, respectively, with limb salvage rates of 84% and 82% and FRR of 52% and 31%, respectively, for the same time periods. Hypoalbuminaemia increased the risk of death (P = .024) and a low score in the MNA questionnaire was associated with increased risk of limb loss (P = .021). More re-admissions were observed among patients revascularised with endovascular techniques (P = .001) and those with initial tissue loss (P = .001). Conclusions: Malnutrition is a very prevalent and potentially treatable factor, which has great impact on the vital and functional prognosis of patients with lower limb critical ischaemia

Chitosan-coated mesoporous MIL-100(Fe) nanoparticles as improved bio-compatible oral nanocarriers.

Nanometric biocompatible Metal-Organic Frameworks (nanoMOFs) are promising candidates for drug delivery. Up to now, most studies have targeted the intravenous route, related to pain and severe complications; whereas nanoMOFs for oral administration, a commonly used non-invasive and simpler route, remains however unexplored. We propose here the biofriendly preparation of a suitable oral nanocarrier based on the benchmarked biocompatible mesoporous iron(III) trimesate nanoparticles coated with the bioadhesive polysaccharide chitosan (CS). This method does not hamper the textural/structural properties and the sorption/release abilities of the nanoMOFs upon surface engineering. The interaction between the CS and the nanoparticles has been characterized through a combination of high resolution soft X-ray absorption and computing simulation, while the positive impact of the coating on the colloidal and chemical stability under oral simulated conditions is here demonstrated. Finally, the intestinal barrier bypass capability and biocompatibility of CS-coated nanoMOF have been assessed in vitro, leading to an increased intestinal permeability with respect to the non-coated material, maintaining an optimal biocompatibility. In conclusion, the preservation of the interesting physicochemical features of the CS-coated nanoMOF and their adapted colloidal stability and progressive biodegradation, together with their improved intestinal barrier bypass, make these nanoparticles a promising oral nanocarrier.

Characterization of the autoimmune response against the nerve tissue S100ß in patients with type 1 diabetes.

Type 1 diabetes results from destruction of insulin-producing beta cells in pancreatic islets and is characterized by islet cell autoimmunity. Autoreactivity against non-beta cell-specific antigens has also been reported, including targeting of the calcium-binding protein S100ß. In preclinical models, reactivity of this type is a key component of the early development of insulitis. To examine the nature of this response in type 1 diabetes, we identified naturally processed and presented peptide epitopes derived from S100ß, determined their affinity for the human leucocyte antigen (HLA)-DRB1*04:01 molecule and studied T cell responses in patients, together with healthy donors. We found that S100ß reactivity, characterized by interferon (IFN)-γ secretion, is a characteristic of type 1 diabetes of varying duration. Our results confirm S100ß as a target of the cellular autoimmune response in type 1 diabetes with the identification of new peptide epitopes targeted during the development of the disease, and support the preclinical findings that autoreactivity against non-beta cell-specific autoantigens may have a role in type 1 diabetes pathogenesis.

Ictiosis arlequín / Harlequin ichthyosis

No disponible

Rapid isolation of single-chain antibodies by phage display technology directed against one of the most potent marine toxins: Palytoxin.

Several recombinant antibodies against one of the most potent marine toxins, Palytoxin (PlTX), were obtained using two naive human semi-synthetic phage display libraries (Tomlinson I and J) as an effective method for generating specific anti-toxin single-chain variable fragment (scFv) antibodies. After four rounds of panning and selection on free palytoxin adsorbed immunotubes, individual clones were isolated, sequenced and characterized by Enzyme-Linked Immunosorbent Assay (ELISA). Four phage-antibody clones specifically recognized the toxin. A competitive ELISA assay was optimized with one of these phage antibodies giving a very reproducible standard curve with a linear regression (R(2)=0.9945), showing a working range of 0.0005-500ngmL(-1). Several spiked shellfish samples were analysed by competitive ELISA to determine the accuracy of the assay, with a mean recovery rate of 90%. This study demonstrates that phage display libraries provide a valuable system for the easy and rapid generation of specific antibody fragments directed against difficult antigenic targets, such as free small molecules. Large-scale, low-cost production of anti-palytoxin scFv antibodies in Escherichia coli (E. coli) is an exciting prospect for the development of rapid and simple detection methods. Our results suggest that anti-palytoxin phage antibodies could be a valuable tool with competitive ELISA to detect palytoxin in natural shellfish samples.

[Thyroid disorders and childhood rheumatic diseases]. / Alteraciones tiroideas y enfermedades reumáticas infantiles.

INTRODUCTION: The relationship between thyroid dysfunction and autoimmune diseases has mainly been described in adults. The aim of this study was to analyse the prevalence and characteristics of thyroid abnormalities in children with rheumatic diseases. PATIENTS AND METHOD: One hundred and forty-five patients (109 girls and 36 boys) from a rheumatology paediatric unit were studied for two years. The diagnoses were: juvenile idiopathic arthritis (JIA) (n=115), lupus (n=17), juvenile dermatomyositis (n=5), scleroderma (n=4), and one case each of the following: mixed connective mixed disease, CINCA syndrome (chronic infantile neurological, cutaneous and articular), TRAPS (tumour necrosis factor receptor-associated periodic syndrome), and familial mediterranean fever. T4 and TSH levels were carried out, and if these showed abnormalities, antithyroid antibodies (ATA) were determined. RESULTS: Six girls aged between 2 and 17 years old had thyroid abnormalities. Three had JIA and three had lupus. Five were diagnosed with autoimmune hypothyroidism, with high ATA levels, and there was one case of hyperthyroidism. All of the patients with thyroid dysfunction had positive antinuclear antibodies (ANA), compared to 34.5% of the rest of the patients (p=0.003). CONCLUSIONS: The prevalence of thyroid abnormalities in children with rheumatic disease was 4.14% to 7.9% in JIA patients with positive ANA, and up to 17.6% with lupus. The majority of patients were asymptomatic. Thyroid hormones should be determined when rheumatic disease is diagnosed and periodically afterwards.

Alteraciones tiroideas y enfermedades reumáticas infantiles / Thyroid Disorders and Childhood Rheumatic Diseases

Introducción: la asociación de trastornos tiroideos y enfermedades autoinmunitarias ha sido descrita en adultos y, en menos ocasiones, en niños. El objetivo de este trabajo es analizar la prevalencia y las características de las alteraciones tiroideas en niños con enfermedades reumáticas. Pacientes y método: se estudió a 145 pacientes (109 mujeres y 36 varones) atendidos en una unidad de reumatología pediátrica durante 2 años. Los diagnósticos fueron: artritis idiopática juvenil (AIJ) (n=115), lupus (n=17), dermatomiositis juvenil (n=5), esclerodermia (n=4) y 1 caso de cada uno de los siguientes: enfermedad mixta del tejido conectivo, síndrome CINCA (chronic infantile neurologic cutaneous and articular), TRAPS (tumor necrosis factor receptor-associated periodic syndrome) y fiebre mediterránea familiar. En todos se determinaron las concentraciones de T4 y TSH, y si estaban alterados, se determinaban los anticuerpos antitiroideos (ATA). Resultados: 6 niñas tuvieron alteración tiroidea, con edades de 2 a 17 años; 3 tenían AIJ y 3, lupus; 5 fueron diagnosticadas de hipotiroidismo autoinmunitario, con ATA elevados, y 1 caso, de hipertiroidismo. El 100% de los pacientes con alteración tiroidea tenían anticuerpos antinucleares (ANA) positivos, frente al 37,4% de los restantes (p=0,003). Conclusiones: La prevalencia de alteraciones tiroideas en niños con enfermedad reumática fue del 4,14%, y aumentó al 7,9% en AIJ con ANA positivos y al 17,6% en lupus. La mayoría estaban asintomáticos. La determinación de hormonas tiroideas debería realizarse al diagnóstico de enfermedad reumática y de forma periódica después (AU)

Introduction: The relationship between thyroid dysfunction and autoimmune diseases has mainly been described in adults. The aim of this study was to analyse the prevalence and characteristics of thyroid abnormalities in children with rheumatic diseases. Patients and method: One hundred and forty-five patients (109 girls and 36 boys) from a rheumatology paediatric unit were studied for two years. The diagnoses were: juvenile idiopathic arthritis (JIA) (n=115), lupus (n=17), juvenile dermatomyositis (n=5), scleroderma (n=4), and one case each of the following: mixed connective mixed disease, CINCA syndrome (chronic infantile neurological, cutaneous and articular), TRAPS (tumour necrosis factor receptor-associated periodic syndrome), and familial mediterranean fever. T4 and TSH levels were carried out, and if these showed abnormalities, antithyroid antibodies (ATA) were determined. Results: Six girls aged between 2 and 17 years old had thyroid abnormalities. Three had JIA and three had lupus. Five were diagnosed with autoimmune hypothyroidism, with high ATA levels, and there was one case of hyperthyroidism. All of the patients with thyroid dysfunction had positive antinuclear antibodies (ANA), compared to 34.5% of the rest of the patients (p=0.003). Conclusions: The prevalence of thyroid abnormalities in children with rheumatic disease was 4.14% to 7.9% in JIA patients with positive ANA, and up to 17.6% with lupus. The majority of patients were asymptomatic. Thyroid hormones should be determined when rheumatic disease is diagnosed and periodically afterwards (AU)

Inmunotecnología aplicada al campo marino / Immunotechnology applied to the marine field

Gracias a sus innumerables aplicaciones, la innovadora técnica de producción de anticuerpos monoclonales (AcsMo) diseñada por los Dres. Köhler y Milstein en 1975 ha revolucionado no sólo el campo biomédico, sino a diversos ámbitos científicos. Aquí mostramos algunos ejemplos de su aplicación en los campos de la Biología y Ecología marinas. España es una potencia mundial en cuanto a producción mejillonera, y cuenta con importantes explotaciones de otras especies de bivalvos. Con el fin de optimizar el rendimiento de esta actividad existen al menos tres aspectos en los que la Inmunotecnología promete ser una herramienta de gran utilidad: 1) Los problemas asociados a las toxinas marinas producidas por floraciones de microalgas tóxicas, obligando al cese de la extracción de bivalvos. Los riesgos podrían ser minimizados mediante una mejora en la monitorización de estos episodios con ayuda de los AcsMo. 2) Detección de toxinas en los bivalvos. El método más utilizado internacionalmente es el bioensayo (inyección de ratones con extractos de bivalvos), pero se están buscando métodos alternativos utilizando AcsMo frente a algunas de las toxinas. 3) Desarrollo de técnicas inmunológicas que permitan la discriminación rápida y fiable de las larvas de mejillón y las larvas de otras especies de bivalvos (muy semejantes morfológicamente). Esto permitiría asesorar al sector mejillonero para optimizar la obtención de cría de mejillón. Así, la Inmunotecnología abre enormes posibilidades en el campo marino, como son la discriminación de especies, mejora de la acuicultura, control de toxinas, estudios ecológicos, o el estudio del sistema inmune de diversos organismos marinos

Thanks to its innumerable applications, the innovative technique of monoclonal antibodies (mAbs) developed by Köhler and Milstein in 1975 has revolutionized not only the biomedical field, but also other sciences. Here, we show some examples of its potential application in Marine Biology and Ecology, especially in the mussel sector and with marine toxins. Spain is an important world producer of mussels and other bivalves, such as oysters and clams. There are at least three aspects in which immunology promises to be a powerful tool for helping to optimize the yield of this activity. These are related to: 1) The problems associated with the marine toxins produced during blooms of toxic microalgae species, which force a halt in the production of bivalves. The use of mAbs to improve the monitoring of toxic algae blooms could minimize such problems. 2) The detection of toxins in the bivalves. Although the most commonly used method, internationally, is a bioassay (injection of mice with bivalve extracts), immunoassays using mAbs against the toxins may be an alternative method. 3) The development of immunological techniques for an accurate identification of mussel larvae: the mAbs can distinguish mussel larvae from other bivalve larvae (very similar in morphology), allowing analysis of the spatio-temporal distribution of the larvae with the aim of optimizing the production of mussels. Moreover, the use of immunological techniques is helping to improve species discrimination, fishing control, the handling of aquaculture, toxin controls and ecological studies, such as those about the immune system of diverse marine organisms

Informe sobre el 16 Congreso Europeo de Inmunología/1ª Reunión Conjunta de las Sociedades Europeas Nacionales de Inmunología / The 16th European Congress of Immunology/1st Joint Meeting of European National Societies of Immunology: a report

En estos comentarios se analizan algunos aspectos organizativos y de contenido del 16 Congreso Europeo de Inmunología/ 1ª Reunión Conjunta de las Sociedades Europeas Nacionales de Inmunología, celebrado en París del 6 al 9 de Septiembre de 2006. En particular, se describe la evolución de la inmunología europea en la última década a partir de la comparación de las características y contenidos de este 16 Congreso con el 12 Congreso Europeo de Inmunología de 1994, y se resumen algunas aportaciones relevantes del congreso referidas a procesamiento y presentación de antígeno, señales activadoras intracelulares, subpoblaciones de células T reguladoras, inmunodeficiencias primarias, o el impacto del envejecimiento en el sistema inmune analizado en el simposio satélite sobre «Aging research in immunology: The impact of genomics»

Some aspects concerning the organization and contents of the 16th European Congress of Immunology/1st Joint Meeting of European National Societies of Immunology held in Paris between the 6th and 9th of September are analyzed. Particularly, the evolution of European Immunology in recent years is dissected by comparing the numbers of participants and the topics raised in this congress with those of the 12th European Congress held in 1994. Furthermore, some relevant data on the contents of the Congress are reviewed concerning antigen processing and presentation, intracellular activation signals, regulatory T cell subpopulations, primary immunodeficiencies, or the satellite symposium on «Aging research in immunology: The impact of genomics »

Somatic hypermutation of Ig genes is affected differently by failures in apoptosis caused by disruption of Fas (lpr mutation) or by overexpression of Bcl-2.

The effects of the two main apoptotic pathways on the somatic hypermutation process were analysed. Transgenic mice carrying the V(kappa)Ox1-J(kappa)5 rat transgene were crossed with Fas-deficient lpr mice or with mice overexpressing the Bcl-2 protein. The transgenic V(kappa)Ox1 segment and the endogenous JH4-C(micro) Ig intron from Peyer's patches germinal centre B cells were sequenced to study the intrinsic somatic hypermutation process without the skewing effects of specific antigen selection. The lpr/ox mice displayed, in both regions, a high level of mutations with a normal pattern of substitutions. On the contrary, the bcl-2/ox mice displayed a lower level of mutations with an altered pattern, showing a decreased mutational rate in the intrinsic hotspots of the V(kappa)Ox1 gene. Our results suggest that the lpr mutation does not have a direct effect on the somatic hypermutation process, but rather on the negative selection of B cells in the germinal centres, leading to the accumulation of recurrent mutations. In contrast, Bcl-2 overexpression might influence the somatic hypermutational process either by altering the incorporation of mutations or by enhancing the repair mechanism(s). The present work supports the hypothesis that both apoptotic pathways, Fas and Bcl-2, play distinct roles in the germinal centre reactions.

H24, un anticuerpo monoclonal humano obtenido de un ratón transgénico portador de genes de Igs humanas, reconoce leucemias mieloides y linfomas no Hodgking CD5- humanos / H24: a human monoclonal antibody obtained from mice carrying human Ig genes, recognises human myeloid leukaemia and CD5- Non-Hodgkin's lymphoma

El anticuerpo monoclonal humano H24 fue obtenido de un ratón transgénico portador de los genes para IgM/kappa/lambda humanos, tras ser inmunizado con la línea celular humana U937. H24 es un anticuerpo completamente humano de isotipo IgM/lambda que reconoce específicamente a una proteína de 80 kDa expresada en granulocitos y monocitos humanos, pero ausente en linfocitos en reposo, hematíes, plaquetas o células progenitoras de médula ósea. El anticuerpo monoclonal H24 reconoce a todas las leucemias mieloides (tanto agudas como crónicas) y síndromes mielodisplásicos analizados, siendo capaz de lisar específicamente a las células en presencia de complemento de conejo. Es interesante destacar que H24 no reconoce leucemias de células B tanto agudas, como linfocíticas crónicas o de células plasmáticas, pero sin embargo se une a células de nódulo linfoide de pacientes con linfoma no Hodgking (NHL) CD5-. Así, este anticuerpo parece ser específico de granulocitos, monocitos y células CD5- de NHL, lo que le hace ser un candidato de potencial utilidad clínica en el tratamiento de procesos linfoproliferativos malignos como leucemias mieloides y algunos linfomas no Hodgking (AU)

[Hematological abnormalities in patients with systemic lupus erythematosus]. / Manifestaciones hematológicas en el lupus eritematoso sistémico.

Haematological abnormalities are frequently encountered in patients with systemic lupus erythematosus (SLE). Anaemia is the most common hematological abnormality in SLE, it is multifactorial. The most common form of anaemia is that of chronic disease, and it is relate with inflammatory cytokines. Other tips of anaemia are: iron deficiency anaemia, autoimmune haemolytic anaemia, pure red cell aplasia. Leucopenia is related to neutropenia and/or lymphopenia. Thrombocytopenia is common, autoimmune and associated with a decreased survival. The presence of antiphospholipid antibodies increase risk of thrombosis in patients with SLE.

Manifestaciones hematológicas en el lupus eritematoso sistémico / Haematological abnormalities in patients with systemic lupus erythematosus

Las alteraciones hematológicas son frecuentes en el lupus eritematoso sistémico (LES). La anemia es la más común y es de naturaleza multifactorial. El tipo más frecuente es la anemia de las enfermedades crónicas, que está en relación con las citoquinas de la inflamación; otros tipos son: la anemia ferropénica, anemia hemolítica autoinmune, aplasia pura de glóbulos rojos. La leucopenia está en relación a la neutropenia y/o linfopenia. La trombocitopenia es común, su causa es autoinmune y se asocia a disminución de la sobrevida. La presencia de anticuerpos antifosfolípidos (AAF) incrementa el riesgo de trombosis en el LES (AU)

Production of antigen-specific human monoclonal antibodies: comparison of mice carrying IgH/kappa or IgH/kappa/lambda transloci.

Here we compare human monoclonal antibody (MAb) production from mouse strains that carry disruptions of their endogenous mouse IgH/IgK loci and harbor human IgM + Igkappa(BABkappa) or human IgM + Igkappa + IgA transloci (BABkappa,lambda). We found that whereas both strains proved effective for the isolation of antigen-specific IgM antibodies, many of the IgM MAbs elicited from BABkappa comprise human mu chains that are associated with mouse lambda chains. In contrast, BABkappa,lambda mice gave rise to fully functional, polymeric human IgM antibodies comprising both human IgH and human IgL chains. Therefore, the inclusion of a human Iglambda translocus (in addition to the human IgH + Igkappa transloci) not only diminishes problems of endogenous mouse Iglambda expression but also provides a strain of mice that yields fully human MAbs to a wide range of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor cell lines, and an immunoglobulin idiotype.

The response in old mice: positive and negative immune memory after priming in early age.

To analyze the effect of age in both B and T cell compartments of the immune system, we have studied the anti-dextran (Dx) B512 humoral immune response in aged C57BL/6 mice. We have used Dx in its native form, which induces a thymus-independent (TI) response, or conjugated to chicken serum albumin (CSA), which induces a thymus-dependent (TD) response. We have also analyzed the adjuvant effect of cholera toxin (CT) in both types of responses. Our results show that the B cell compartment is not greatly affected by age as demonstrated in the TI responses and that CT is a powerful adjuvant despite the age of the animals. However, we found a severe age-associated impairment of TD responses. We conclude that the first antigenic challenge deeply influences further antigenic responses in a positive or negative manner. Priming in early life with native Dx (TI) inhibited late TD responses in aged mice, even when the primary immunization had occurred a long time ago. This negative memory affects posterior TD responses both in the quantity and in the affinity of the response. However, immunization at an early age with TD priming (CSA-Dx) provoked a long-lasting immune memory that abolished in part the age-associated impairment of the response. Our results suggest that protocols of vaccination with TI antigens may not be a convenient strategy, because the development of further optimal immune responses to the same antigen can be impaired.

Mejorando la supervivencia en el trasplante de órgano sólido. De la irradiación total a la utilización de anticuerpos monoclonales / Improving solid organ transplant survival. From total irradiation to the use of monoclonal antibodies

Desde que se realizaran los primeros trasplantes de órganos a seres humanos a primeros de los años 50, el número de trasplantes se ha incrementado de forma muy significativa en muchos países, destacando especialmente España como el primer país del mundo en cuanto a trasplantes de riñón e hígado. Si bien los aspectos quirúrgicos y tecnológicos han avanzado extraordinariamente, el gran reto del trasplante sigue constituyendo la pérdida del mismo por rechazo, mediado por la respuesta inmunológica del receptor. Una parte muy importante del éxito de la aceptación de los trasplantes se encuentra en la utilización de terapia inmunosupresora, que ha experimentado un gran desarrollo desde sus orígenes. En este trabajo se realiza una revisión de las drogas inmunosupresoras que han sido utilizadas para evitar el rechazo de transplantes de órgano sólido, incluyendo también el uso de anticuerpos monoclonales dirigidos frente a distintos componentes de la respuesta inmunitaria (AU)