Clinical management strategies for recipients with renal graft loss / 器官移植

With the maturity of kidney transplantation, introduction of new immunosuppressive drugs and improvement of immunosuppressive regimen, the short-term survival rate of kidney transplant recipients has been significantly improved, whereas the long-term survival rate has not been significantly elevated. Kidney transplant recipients may have the risk of renal graft loss. Clinical management after renal graft loss is complicated, including the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy. These management procedures directly affect clinical prognosis of patients with renal graft loss. Nevertheless, relevant guidelines or consensuses are still lacking. Clinical management of patients after renal graft loss highly depend upon clinicians’ experience. In this article, the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy were reviewed, aiming to provide reference for prolonging the survival and improving the quality of life of these patients.

Pharmacogenetic testing improves treatment responses in patients with PLA2R-related membranous nephropathy / 南方医科大学学报

OBJECTIVE@#To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients.@*METHODS@#A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment.@*RESULTS@#Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05).@*CONCLUSION@#Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.

Risk factors associated with diabetes after liver transplant

ABSTRACT Objective: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after liver transplant that negatively affects a recipient's survival and graft function. This study aims to identify risk factors associated with diabetes after liver transplant. Materials and methods: This is a cross-sectional study conducted from September to November 2019. Data collection was performed by chart review, and patients were divided into 3 groups: patients without diabetes mellitus (DM), patients with pre-transplant diabetes mellitus, and patients with PTDM. Results: Two hundred and forty-seven patients' medical charts were screened, and 207 patients were included: 107 without DM, 42 with pre-transplant DM, and 58 with PTDM. The leading cause for liver transplant was hepatitis C, followed by hepatocellular carcinoma secondary to alcohol. There was a higher exposure to tacrolimus in patients without DM ( P = 0.02) and to ciclosporin in patients with pre-transplant DM, compared to others ( P = 0.005). Microscopic interface inflammatory activity was more severe in patients without DM as well as those with PTDM ( P = 0.032). There was a higher prevalence of steatosis in recipients with pre-transplant DM than there was in others ( P < 0.001). Multivariate logistic regression identified the following independent risk factors for DM: cirrhosis due to alcohol, hepatitis C, and triglycerides. For PTDM, these independent risk factors were cirrhosis due to alcohol, hepatitis C, and prednisone exposure. Conclusion: Alcoholic cirrhosis is a risk factor for PTDM in liver recipients. Liver transplant recipients with a pre-transplant history of cirrhosis due to alcohol, hepatitis C, and prednisone exposure deserve more caution during PTDM screening.

Polimorfismos em genes envolvidos na farmacodinâmica de tacrolimo e everolimo e sua relação com a resposta ao tratamento imunossupressor, em receptores de transplante renal / Polymorphisms in pharmacodynamics-related genes of tacrolimus and everolimus and their relationship with the response to immunosuppressant treatment, in kidney transplant recipients

O monitoramento de imunossupressores, como os inibidores de calcineurina ou de mTOR, é essencial para evitar desfechos clínicos desfavoráveis, em receptores de transplante renal. Polimorfismos em genes envolvidos na farmacocinética têm sido associados com variabilidade na resposta a imunossupressores, porém o papel de polimorfismos em genes envolvidos na farmacodinâmica é pouco conhecido. O objetivo deste estudo foi investigar a influência de polimorfismos de MTOR, PPP3CA, FKBP1A, FKBP2 e FOXP3, genes envolvidos na farmacodinâmica de imunossupressores, sobre a resposta clínica a tacrolimo e everolimo, em receptores de transplante renal. Foram incluídos 269 pacientes do ensaio clínico original (NCT01354301), realizado no Hospital do Rim e Hipertensão da UNIFESP, e randomizados em três esquemas imunossupressores: tacrolimo 0,05 mg/kg/dia com everolimo 1,5 mg/dia (TAC5/EVR); tacrolimo 0,1 mg/kg/dia com everolimo 1,5 mg/dia (TAC10/EVR); e tacrolimo 0,1 mg/kg/dia com micofenolato de sódio (TAC10/MFS). Foram coletados dados clínicos e laboratoriais, tais como o monitoramento de imunossupressores e desfechos de eficácia de segurança. Os polimorfismos nos genes MTOR (c.4731G>A, c.1437T>C, c.2997C>T); PPP3CA (c.249G>A); FKBP1A (n.259+243936T>C); FBKP2 (c.-2110G>T) e FOXP3 (c.-23+2882A>C, c.-22-902A>G) foram analisados por PCR em tempo real. As frequências alélicas dos polimorfismos estudados foram similares às da população global do projeto 1000genomes. O tratamento com everolimo e tacrolimo em maior dose (TAC10/EVR) foi associado com menor taxa de filtração glomerular estimada (TFGe) e maior creatinina sérica. Enquanto que o tratamento com tacrolimo e micofenolato de sódio (TAC10/MFS) foi associado com maior número de episódios de infecção por citomegalovirus, no 1° ano pós-transplante. Com relação aos desfechos de eficácia, os portadores do genótipo CC de MTOR c.1437T>C e FOXP3 c-23+2882A>C apresentaram maiores concentrações de creatinina sérica, no 12° mês (p<0,05). O polimorfismo FOXP3 c.-23+2882A>C foi associado com maior probabilidade de creatinina sérica aumentada (OR=1,75; IC95%=1,07-2,86; p=0,025). Os resultados da análise de regressão logística mostraram que o alelo MTOR c.4731G (genótipos AG+GG) foi associado com maior risco de rejeição aguda (OR=3,37; IC95%=1,10-10,30; p=0,033). Os portadores do alelo c.4731G apresentaram maior incidência cumulativa de episódios de rejeição, no 1° ano pós-transplante. Com relação aos desfechos de segurança, a variante FKBP2 c.-2110G>T (genótipo GG) foi associada com maior risco de leucopenia (OR=7,10; IC95%=1,81-27,87; p=0,025). O polimorfismo FKBP1A n.259+24936T>C (alelo C) foi associado com maior risco de constipação (OR=2,52; IC95%=1,13 - 5,61; p=0,024), enquanto que os polimorfismos FOXP3 c.-22-902A>G (alelo A) e c.-23+2882A>C (alelo A) foram associados, respectivamente, com maior risco de epigastralgia (OR=2,15; IC95%=1,01-4,56; p=0,047) e náuseas e/ou vômitos (OR=2,38; IC95%=1,05-5,38; p=0,038). O risco de apresentar dislipidemia foi maior nos portadores dos genótipos FKBP2 c.-21110GG (OR=1,92; IC95%=1,01-3,69; p=0,049) e FOXP3 c.-22-902GG (OR=2,06; IC95%=1,08-3,92; p=0,028). Em conclusão, os polimorfismos de genes MTOR, FKBP1A, FKBP2 e FOXP3 influenciam na função renal do enxerto e estão associados com risco de rejeição aguda e de eventos adversos, em receptores de transplante renal

The monitoring of immunosuppressive drugs, such as calcineurin and mTOR inhibitors, is essential to avoid undesirable kidney transplant outcomes. Polymorphisms in pharmacokinetics-related genes have been associated with variability in the response to immunosuppressive drugs, but the role of polymorphisms in pharmacodynamics-related genes is little known. The aim of this work was to investigate the influence of polymorphisms in MTOR, PPP3CA, FKBP1A, FKBP2 and FOXP3, genes involved in the pharmacodynamics of immunosuppressive drugs, on the clinical response to tacrolimus and everolimus in kidney transplant recipients. Two-hundred seventy-five kidney transplant recipients were included in this study, among the enrolled in the original clinical trial (NCT01354301) carried out at the Hospital do Rim e Hipertensão/UNIFESP, and randomized in three immunosuppressive treatments: tacrolimus 0.05 mg/kg/day with everolimus 1.5 mg/day (TAC5/EVR); tacrolimus 0.1 mg/kg/day with everolimus 1.5 mg/day (TAC10/EVR); and tacrolimus 0.1 mg/kg/day with sodium mycophenolate (TAC10/MFS). Clinical and laboratory data, including immunosuppressive drug monitoring, efficacy and safety outcomes, were recorded. Polymorphisms on the MTOR (c.4731G>A, c.1437T>C, c.2997C>T); PPP3CA (c.249G>A); FKBP1A (n.259+243936T>C); FBKP2 (c.-2110G>T) and FOXP3 (c.-23+2882A>C, c.-22-902A>G) genes were analyzed by real-time PCR. Allelic frequencies of the studied polymorphisms were similar to those of the global population reported by the 1000genomes project. Treatment with everolimus and high-dose tacrolimus (TAC10/EVR) was associated with lower estimated glomerular filtration rate (eGFR) and higher serum creatinine. Meanwhile treatment with tacrolimus and sodium mycophenolate (TAC10/MFS) was associated with higher number of cytomegalovirus infections, at 1-year post-transplantation. With regard to the kidney efficacy outcomes, the carriers of the CC genotype of MTOR c.1437T>C and FOXP3 c.-23+2882A>C had higher serum creatinine, at month 12 (p<0.05). The FOXP3 c.-23+2882A>C polymorphism was associated with high likelihood of increased serum creatinine (OR=1.75, 95%IC=1.07-2.86, p=0.025). The results of the logistic regression analysis showed that the allele MTOR c.4731G (AG+GG genotypes) was associated with higher risk of acute rejection (OR=3.37, 95%IC=1.10-10.30, p=0.033). The carriers of the c.4731G allele showed higher cumulative incidence of acute rejection episodes at 1-year post-transplantation. With regard to kidney safety outcomes, the FKBP2 c.-2110G>T variant (GG genotype) was associated with higher risk of leucopenia (OR=7.10, 95%IC=1.81-27.87, p=0.025). The FKBP1A n.259+24936T>C (C allele) polymorphism was associated with higher risk of constipation (OR=2.52, 95%IC=1.13-5.61, p=0.024), whilst FOXP3 c.-22 902A>G (A allele) and c.-23+2882A>C (A allele) were associated, respectively, with higher risk of epigastric pain (OR=2.15, 95%IC=1.01-4.56, p=0.047) and nausea and/or vomiting (OR=2.38, 95%IC=1.05-5.38, p=0.038). The risk of developing dyslipidemia was higher in carriers of the genotypes FKBP2 c.-21110GG (OR=1.92, 95%CI=1.01-3.69, p=0.049) and FOXP3 c.-22-902GG (OR=2.06, 95%CI=1.08-3.92, p=0.028). In conclusion, the polymorphisms in the MTOR, FKBP1A, FKBP2 and FOXP3 genes influence renal graft function and are associated with risk of acute rejection and adverse events in renal transplant recipients

Establishment of an allogenetic skin transplant model in mice for evaluating immunosuppressive drugs / 中国药理学通报

Aim To establish an allogenetic mouse skin trans-plant model,in order to provide a research model for immunosup-pressive drugs. Methods Skins from the ears of C57BL/6 mice were transplanted to the back of BALB/c mice and skin isografts ( BALB/c mice to BALB/c mice) were used as control. Cyclos-porin A( CsA) was used as a model compound to test the imm-nosuppresive effect on allogenetic graft rejection. Following the transplation and CsA treatment, the graft rejection score and graft skin survival rate were quantified. Four and nine days after transplantation,serum IL-4,IL-12 and IFN-γ levels were meas-ured using ELISA kits. Twelve days after transplantation, mice were sacrificed. The weight of spleen and thymus was obtained, and CD4 + and CD8 + population of spleenic T cells were ana-lyzed using flow cytometer. Histological features were assessed by hematoxylin-eosin( HE) staining of formalin-fixed, paraffin-em-bedded graft skins. Results After transplantion, the graft rejec-tion score increased and graft skin survival rate decreased gradu-allly. Serum IL-12 and IFN-γ levels of allograft mice increased markedly. Compared with those of isograft mice, mice with skin allograft displayed a significant increase in the percentage of the CD8 + T cell subpopulation. Remarkable inflammation, such as edema, inflammatory cell infiltration were observed in allograft mice. Compared with saline treated mice, CsA significantly re-duced the graft rejection score and improved survival rate of skin grafts. And also, CsA treated mice had smaller spleen and thy-mus. Mice that received high doses of CsA had significantly less CD8 + T cells than those treated with saline. Moreover, allograft skins in mice that received CsA had less inflammation. Conclu-sions Allogenetic mouse skin transplantation exhibits acute graft rejection. CsA can inhibit the rejection in a dose dependent manner.

Líquen plano hipertrófico: uma proposta terapêutica / Hyperthrofic lichen planus: another therapeutic approach

O líquen plano hipertrófico é uma variante do líquen plano. Clinicamente, caracterizam-se por placas hiperceratósicas, simétricas, de coloração cinza-violácea, com predileção pela região pré-tibial. O objetivo deste trabalho é apresentar um caso clínico de líquen plano hipertrófico que evoluiu com resposta clínica satisfatória.

Progress in Pharmacogenomics Research on Immunosuppressive Drugs / 中国药师

Immunosuppressive drugs used in organ transplantation are highly effective in preventing acute rejection. However,the clinical use of the drugs is complicated by the fact that they display highly variable pharmacokinetics and pharmacodynamics among in-dividual patients. The influence of genetic variation on the interindividual variability in immunosuppressive drug disposition,efficacy and toxicity has been explored in recent years. The review summarized all kinds of immunosuppressants and their relationship with ge-netic polymorphisms,including the SNPs of related enzymes about pharmacokinetics and pharmacodynamics,the SNPs of donor and tar-get site. The review focused on the current situation and progress in the related research areas.

Prevalência de doenças neoplásicas em pacientes com artrite reumatoide / Prevalence of neoplasic diseases in patients with rheumatoid arthritis

Justificativa: A artrite reumatoide (AR) é uma doençainflamatória progressiva responsável por altas taxas demorbidade e mortalidade além de diminuir a qualidadede vida dos pacientes. Estudos relatam maior prevalênciade neoplasias em pacientes com AR. Objetivo:Investigar a prevalência de doenças neoplásicas empacientes com artrite reumatoide, bem como verificarsua associação com medicamentos imunossupressores.Métodos: Foram revisados 535 prontuários de pacientescom diagnóstico de AR em acompanhamento porum ambulatório de reumatologia. Todos os pacientesincluídos preenchiam critérios classificatórios para artritereumatoide do Colégio Americano de Reumatologiade 1987. Coletaram-se dados demográficos dos pacientes,de medicamentos utilizados no tratamento daAR e de prevalência de neoplasias. Resultados: Há umaprevalência de tumores em pacientes com artrite reumatoidede 10,1% (n=36/336) existindo tumores malignosem 7,7% (26/336) deles. Os tumores malignosmais comuns foram os de mama, útero e linfoproliferativos. Pode ser verificado que a artrite reumatoide surgeem idade mais precoce no paciente que desenvolveutumor maligno. Embora apenas 5% dos pacientes comAR utilizaram azatioprina, esta droga esteve associadoao aparecimento de neoplasia maligna em 16,6% daamostra estudada (p=0,05). Conclusão: O risco de neoplasiasé elevado em pacientes com artrite reumatoide.O uso de imunossupressores tem influência limitada noseu aparecimento exceto pela azatioprina.

Background: Rheumatoid arthritis is a progressiveinflammatory disease responsible for high rates ofmorbidity and mortality besides decreasing the qualityof life of patients. Autoimmune diseases have higherprevalence of tumors. Objective: This study aims atinvestigating the prevalence of neoplasic diseases inpatients with rheumatoid arthritis and its associationwith immunosuppressive drugs. Methods: This is aretrospective study. The charts of 535 patients whowere being assisted by a rheumatologic clinic werereviewed. All patients included fulfilled the fourclassification criteria for rheumatoid arthritis of theAmerican College of Rheumatology. Demographic andserologic data, as well as information concerning themedicines used to treat rheumatoid arthritis and theprevalence of tumors were collected. Results: Thereis a prevalence of malignant tumors in patients withrheumatoid arthritis of 10.1% (n=36/336) and 7.7%(26/336) of them were malignant . The most commonmalignant tumors were breast and uterus cancer andlymphoproliferative diseases. It can be verified that therheumatoid arthritis arises at an earlier age when thepatient develops tumor. The use of azathioprine wasassociated with malignancy in 16.6% of the sample(p=0.05). Conclusion: The risk of cancer is elevated inpatients with rheumatoid arthritis. Immunosuppressivedrugs have limited influence in the appearance ofmalignant tumors except azathioprine.

Terapia de hepatitis autoinmune no respondedora a esteroides / Autoimmune hepatitis with no response to steroids

Autoimmune hepatitis refractory to corticod therapy is infrequent. Generally, it occurs in severe cases and in young patients. There are several treatment options, including higher doses of the regular medications and, eventually, the use of other immunosuppressive drugs with higher potency, such as mycophenolate, cyclosporin, tacrolimus, among others.

La hepatitis autoinmune refractaria a terapia corticoidal afortunadamente es poco frecuente. Generalmente ocurre en casos de presentación más grave y en pacientes jóvenes. Existen varios esquemas para su enfrentamiento, incluyendo mayores dosis de terapia habitual y, eventualmente, el uso de otros fármacos inmunosupresores de mayor potencia como micofenolato, ciclosporina, tacrolimus y otros.

Imnunosupresión tras el trasplante hepático: más nefrones, menos hepatocarcinoma / Immunosupression after liver transplant: more nephrons, less hepatocellular carcinoma

Following liver transplantation, immunosuppressive drugs are responsible for a significant proportion of the morbidity and mortality. Thus, renal failure and hepatocellular carcinoma recurrence are critically related to the use of immunosuppressive drugs. In this article, the immunosuppressive strategies that allow preservation of the renal function and minimization of the recurrence rate of hepatocellular carcinoma are detailed.

Tras el trasplante hepático, la inmunosupresión es responsable de buena parte de la morbi-mortalidad asociada. El deterioro de la función renal y la recurrencia del hepatocarcinoma son ámbitos donde la inmunosupresión tiene un impacto significativo. En el presente artículo se abordan las estrategias inmunosupresoras que permiten preservar la función renal y minimizar la recurrencia del hepatocarcinoma tras el trasplante hepático.

Líquen plano hipertrófico disseminado: relevante resposta à acitretina / Disseminated hypertrophic lichen planus: relevant response to acitretin

O líquen plano hipertrófico é uma variante do líquen plano, com pronunciada hiperplasia epidérmica em resposta à coçadura persistente. Clinicamente, caracterizam-se por placas hiperceratósicas, simétricas, de coloração cinza-violácea, com predileção pela região pré-tibial. O prurido intenso, a refratariedade aos tratamentos convencionais e a possibilidade de associação de um carcinoma epidermoide às lesões de longa duração impõem um tratamento eficaz. Os corticoides são considerados o tratamento de primeira linha e podem ser aplicados topicamente ou empregados de forma sistêmica. Outras modalidades terapêuticas propostas são a fototerapia com UVB-NB ou PUVA, imunossupressores e retinoides sistêmicos, com destaque para a acitretina. Relatamos um caso com apresentação clínica exuberante e excelente resposta à acitretin, totalizando um seguimento de nove meses.

Hyperthrofic lichen planus is considered a variant of lichen planus with marked epidermal hyperplasia in response to persistent itch. It is clinically, characterized by symmetric hyperkeratotic plaques, of purplish-grey color, often located in the pretibial region. Intense pruritus, refractoriness to conventional treatments and the possibility of association of the long-term injuries with squamous cell carcinoma requires an effective treatment. The first-line treatment is corticosteroids which can be applied either topically or systemically. Other therapeutic modalities proposed are: NB-UVB phototherapy or PUVA, immunosuppressive drugs and systemic retinoids, notably acitretin. We report a case with exuberant clinical presentation of hyperthrofic lichen planus with excellent response to acitretin after nine months of treatment.

Microencapsulación de células y tejido para terapia celular / Cellular and tissue microencapsulation for cellular therapy

Microencapsulation is a technique that protects viable cells in semi-permeable membranes, which allow passage of essential molecules while stopping larger molecules, such as antibodies, involved in the death of transplanted cells. This allows the avoidance of immunosuppressive drugs. Several substances have been used for this purpose, and alginate is one of the most studied and validated. Alginate is extracted from algae present in African and Chilean coasts; different algae can be mixed in variable proportions to produce alginate with distinct characteristics. Commercial alginate evokes an inflammatory response that results in the death of transplanted cells. High purity alginate has already been developed to avoid this issue. There are several applications to this technique, as there are a large number of pathologies that result from the destruction or extraction of tissues, with the consequent loss of function (diabetes mellitus or post-surgical hypoparathyroidism, for example). Finally, there is an additional interest in alginate microencapsulation in this country, given that it can be easily obtained from national algae.

La microencapsulación es una técnica que protege células viables en membranas semi-permeables, que permite el paso de moléculas que son esenciales para la célula y a la vez impide el paso de otras, como los anticuerpos, involucradas en la destrucción celular. Esto permite evitar el uso de drogas inmunosupresoras. Variadas biomacromoléculas pueden ser utilizadas con este fin, siendo el alginato uno de los biopolímeros más validados y estudiados. El alginato es un polisacárido amónico formado por unidades acidas b-L-manurónicas y a-L-gulorónicas, extraído desde algas presentes en costas africanas y chilenas. Así, diferentes algas pueden ser mezcladas en proporciones variables para producir alginatos de distintas características. El alginato comercial produce una respuesta inflamatoria que causa la muerte de las células trasplantadas; ya se han desarrollado alginatos de alta pureza para evitar este problema. Existen varias aplicaciones para esta técnica, ya que existen diversas patologías caracterizadas por una pérdida de función por destrucción o extracción de tejido (por ejemplo, diabetes mellitus o hipoparatiroidismo post-quirúrgico). Esta técnica representa un especial interés en Chile, ya que el alginato puede ser obtenido fácilmente a partir de algas chilenas.

Application of population pharmacokinetics in the rational usage of immunosuppressive drugs / 中国药理学通报

Population pharmacokinetics(PPK),which is based on the principle of statistics,can be used to estimate various inter- and intra-individual factors which affect pharmacokinetics.By using Bayesian estimator,PPK can predict individual pharmacokinetic parameters accurately.PPK is widely used in the immunosuppressive therapy with cyclosporine,tacrolimus,mycophenolic acid and sirolimus.

Mecanismos moleculares de acción de algunas drogas inmunosupresoras / Molecular mechanisms of action of some immunosuppresive drugs

Los tratamientos utilizados para desordenes inmunológicos son de origen empírico, utilizando drogas inmunosupresoras identificadas a través de la selección de un gran número de compuestos naturales y sintéticos. Las drogas inmunosupresoras son ampliamente utilizadas en tratamientos clínicos de desordenes autoinmunes, en la prevención de rechazo a transplantes así como también en desordenes de carácter no autoinmune tales como las alergias. El diseño de las terapias inmunosupresoras está basado en controlar una respuesta inmune exacerbada. La base fisiopatológica de este concepto es en modular la acción de células mononucleares, siendo el principal punto de control las células T. Estas drogas inhiben la función normal de protección del sistema inmune llevando a la aparición de complicaciones en las terapias de inmunosupresión. Las drogas inmunosupresoras tienen diferentes blancos en el proceso de inmunidad celular. Según su modo de acción pueden clasificarse en cuatro categorías: drogas antinflamatorias de la familia de los corticosteroides, inmunosupresoras específicas inhibidoras de la calcineurina, citotóxicas o antiproliferativas y anticuerpos específicos. En este trabajo describimos el mecanismo de acción molecular de agentes inmunosupresores tales como, esteroides, ciclosporina, tacrolimo, azatioprina, ciclofosfamida, sirolimus, mofetil mecofenolato, leflunomida y anticuerpos específicos, para contribuir a la comprensión de cómo utilizar y mejorar estos agentes.

A number of natural and synthetic substances are used in the treatment of immunological disorders. The immunosuppressive drugs are widely utilized in clinical treatments of autoimmune disorders, in the prevention of transplant rejection as well as in non-autoimmune diseases such as allergy. The design of immunosuppressive therapies is based on the control of the exacerbated immune response. The pathophysiologic mean of this concept is to modulate the action of mononuclear cells, being T cells the main targets. Immunosuppressive agents have different molecular targets, and an important drawback in their use is that they also inhibit the normal immune system response. Depending on their mode of action, immunosuppressive drugs can be classified in four different groups: antinflammatory drugs of the corticosteroid family, inhibitors of the calcineurin pathway, cytototoxic or antiproliferative drugs and specific antibodies. In this article, we focus on the molecular action of immunosuppressive drugs such as steroids, cyclosporine, tacrolimus, azathioprine, cyclophosphamide, sirolimus, mycophenolate mofetil, leflunomide and specific antibodies, providing data to characterize and improve the use of these agents.