Targeted therapies for lupus nephritis: Current perspectives and future directions / 中华医学杂志(英文版)

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

Preparation of mouse monoclonal antibodies against the ectodomain of Western equine encephalitis virus E2 (E2ecto) protein / 细胞与分子免疫学杂志

Objective To prepare mouse monoclonal antibodies against the ectodomain of E2 (E2ecto) glycoprotein of Western equine encephalitis virus (WEEV). Methods A prokaryotic expression plasmid pET-28a-WEEV E2ecto was constructed and transformed into BL21 (DE3) competent cells. E2ecto protein was expressed by IPTG induction and presented mainly as inclusion bodies. Then the purified E2ecto protein was prepared by denaturation, renaturation and ultrafiltration. BALB/c mice were immunized with the formulated E2ecto protein using QuickAntibody-Mouse5W as an adjuvant via intramuscular route, boosted once at an interval of 21 days. At 35 days post-immunization, mice with antibody titer above 1×104 were inoculated with E2ecto intraperitoneally, and spleen cells were fused with SP2/0 cells three days later. Hybridoma cells secreting specific monoclonal antibodies were screened by the limited dilution method, and ascites were prepared after intraperitoneal inoculation of hybridoma cells. The subtypes and titers of the antibodies in ascites were assayed by ELISA. The biological activity of the mAb was identified by immunofluorescence assay(IFA) on BHK-21 cells which were transfected with eukaryotic expression plasmid pCAGGS-WEEV-CE3E2E1. The specificity of the antibodies were evaluated with E2ecto proteins from EEEV and VEEV. Results Purified WEEV E2ecto protein was successfully expressed and obtained. Four monoclonal antibodies, 3G6G10, 3D7G2, 3B9E8 and 3D5B7, were prepared, and their subtypes were IgG2c(κ), IgM(κ), IgM(κ) and IgG1(κ), respectively. The titers of ascites antibodies 3G6G10, 3B9E8 and 3D7G2 were 105, and 3D5B7 reached 107. None of the four antibody strains cross-reacted with other encephalitis alphavirus such as VEEV and EEEV. Conclusion Four strains of mouse mAb specifically binding WEEV E2ecto are successfully prepared.

Neumonía por Pneumocystis jirovecii asociada a hemorragia alveolar difusa en un paciente con trasplante renal / Pneumocystis jirovecii pneumonia associated with diffuse alveolar hemorrhage in a renal transplant patient. Case report

La neumonía por Pneumocystis jirovecii es una enfermedad fúngica oportunista descrita principalmente en pacientes con VIH, sin embargo, tras la introducción de la TARV, ha incrementado su incidencia en pacientes con inmunosupresión no asociada a VIH, como neoplasias hematológicas y trasplantes de órganos sólidos. Presentamos el caso de un varón de 17 años, receptor de un trasplante renal, con inmunosupresión prolongada con corticoesteroides, con cuadro clínico de tos, disnea y fiebre. La TC mostró micronódulos pulmonares centrolobulillares y vidrio esmerilado. El LBA fue compatible con hemorragia alveolar difusa (HAD), con RPC positiva para P. jirovecii. Se descartaron otras infecciones y enfermedades autoinmunes. Recibió tratamiento con cotrimoxazol con buena evolución clínica y mejoría radiológica. Si bien las causas más frecuentes de HAD son etiologías autoinmunes como enfermedades reumatológicas o vasculitis, es prioritario descartar causas infecciosas, incluyendo P. jirovecii, ya que el tratamiento dirigido puede tener un impacto significativo en la mortalidad en este grupo de pacientes.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection, described mainly in HIV patients, however, after the introduction of ART, its presentation has increased in patients with non-HIV immunosuppression, such as hematological cancers, solid or hematopoietic stem cell transplantation. We report the case of a 17-year-old male, kidney transplant patient, with prolonged immunosuppression with corticoesteroids, with history of cough, dyspnea, and fever. Chest CT evidences centrilobular pulmonary micronodules with ground glass. BAL was performed compatible with diffuse alveolar hemorrhage, with positive PCR for P. jirovecii. Other infections and autoimmune disease were ruled out. He received treatment with cotrimoxazole with clinical improvement of the patient, and follow up chest CT at the end of treatment showed decrease of pulmonary infiltrates. Although the most frequent causes of DAH are autoimmune etiologies such as rheumatic diseases or vasculitis, it is a priority to rule out infectious causes, including P. jirovecii, since targeted treatment could have a significant impact on mortality outcomes in this group of patients.

Caracterización clínica de la Nefropatía por Poliomavirus BK en pacientes trasplantados renales / Clinical characterization of Polyomavirus BK nephropathy in kidney transplanted patients

INTRODUCCIÓN. La nefropatía por poliomavirus BK resulta un problema emergente en el trasplante renal, pues contribuye a la pérdida temprana de los injertos renales. OBJETIVO. Caracterizar clínicamente a los pacientes trasplantados renales con nefropatía por poliomavirus BK. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, realizado en el Hospital de Especialidades Carlos Andrade Marín en el período 2013-2022, se obtuvo una base de datos anonimizada, 479 pacientes trasplantados renales, de estos se identificaron 37 pacientes que corresponde a un 7,7% con nefropatía por poliomavirus BK, se realizó un análisis con el programa estadístico SPSS v26®. RESULTADOS. La población estuvo caracterizada por pacientes del sexo masculino (56,8%), con una edad media de 48,2 años, el donante cadavérico fue el más frecuente (94,5%), la mayor parte del tratamiento de la nefropatía por poliomavirus BK consistió en cambio de micofenolato sódico a everolimus y se mantuvo con 50% de Tacrolimus y Prednisona (40,5%); al valorar el cambio de los valores de creatinina, los niveles más elevados fueros a los 12 meses cuando la pérdida renal fue temprana (p: 0,042), y de la misma manera a los 12 meses, fueron más elevados los niveles de creatinina cuando el diagnóstico histopatológico fue Nefropatía por Poliomavirus Clase 3 (p: 0,01). DISCUSIÓN. La prevalencia de la nefropatía se mantuvo por debajo del 10% reportado a nivel global, la creatinina empeoró en pacientes con pérdida temprana del injerto renal y con una clase patológica avanzada, hecho reportado en la fisiopatología de la enfermedad. CONCLUSIÓN. La pérdida del injerto renal temprano presentó una creatinina más alta que la tardía. Es recomendable un tamizaje adecuado para la detección temprana del virus BK siendo crucial para prevenir el deterioro de la función renal y limitar la posterior pérdida del injerto.

INTRODUCTION: BK polyomavirus nephropathy is emerging as a significant concern in kidney transplantation, as it contributes to the early loss of renal grafts. OBJECTIVE: The aim of this study was to clinically characterize renal transplant recipients with BK polyomavirus nephropathy. MATERIALS AND METHODS: An observational and descriptive study was conducted at Carlos Andrade Marín Specialties Hospital during the period of 2013 to 2022. An anonymized database comprising 479 renal transplant patients was utilized. Among these, 37 patients, constituting 7.7%, were identified with BK polyomavirus nephropathy. Data analysis was performed using the statistical program SPSS v26®. RESULTS: The study population was predominantly composed of male patients (56.8%) with a mean age of 48.2 years. Deceased donors accounted for the majority (94.5%) of cases. The primary approach for managing BK polyomavirus nephropathy involved transitioning from mycophenolate sodium to everolimus, alongside maintaining a regimen of 50% tacrolimus and 40.5% prednisone. When assessing changes in creatinine values, the highest levels were observed at 12 months, coinciding with early renal loss (p: 0.042). Similarly, at the 12-month mark, elevated creatinine levels were associated with a histopathological diagnosis of Polyomavirus nephropathy Class 3 (p: 0.01). DISCUSSION: The prevalence of nephropathy remained below the globally reported threshold of 10%. Creatinine levels worsened in patients experiencing early graft loss and an advanced pathological classification, aligning with established disease pathophysiology. CONCLUSION: Early renal graft loss was associated with higher creatinine levels compared to delayed loss. Adequate screening for early detection of BK virus is recommended, as it plays a crucial role in preventing renal function deterioration and limiting subsequent graft loss.

Mortalidad de la sepsis en la unidad de cuidados intensivos / Mortality from sepsis in intensive care unit

INTRODUCCIÓN. La sepsis es un estado de disfunción multisistémica, que se produce por una respuesta desregulada del huésped a la infección. Diversos factores influyen en la gravedad, manifestaciones clínicas y progresión de la sepsis, tales como, heterogeneidad inmunológica y regulación dinámica de las vías de señalización celular. La evolución de los pacientes depende del tratamiento oportuno, las escalas de puntuación clínica permiten saber la mortalidad estimada. OBJETIVO. Evaluar la mortalidad en la unidad de cuidados intensivos; establecer el manejo y la utilidad de aplicar paquetes de medidas o "bundlers" para evitar la progresión a disfunción, fallo multiorgánico y muerte. METODOLOGÍA. Modalidad de investigación tipo revisión sistemática. Se realizó una búsqueda bibliográfica en bases de datos como Google académico, Mendeley, ScienceDirect, Pubmed, revistas como New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. Se obtuvo las guías "Sobreviviendo a la sepsis" actualización 2021, 3 guías internacionales, 10 estudios observacionales, 2 estudios multicéntricos, 5 ensayos aleatorizados, 6 revisiones sistémicas, 5 metaanálisis, 1 reporte de caso clínico, 4 artículos con opiniones de expertos y actualizaciones con el tema mortalidad de la sepsis en UCI con un total de 36 artículos científicos. RESULTADOS. La mortalidad de la sepsis en la unidad de cuidados intensivos, fue menor en el hospital oncológico de Guayaquil, seguido de Australia, Alemania, Quito, Francia, Estados Unidos de Norteamérica y Vietnan, La mortalidad más alta se observa en pacientes con enfermedades del tejido conectivo. DISCUSIÓN. La aplicación de los paquetes de medidas o "bundlers" en la sepsis, se asocia con una mejor supervivencia y menores días de estancia hospitalaria. CONCLUSIÓN. Las escalas SOFA, APACHE II y SAPS II ayudan a predecir la mortalidad de forma eficiente, en la detección y el tratamiento temprano en pacientes con enfermedades agudas y de alto riesgo.

INTRODUCTION. Sepsis is a state of multisystem dysfunction, which is caused by a dysregulated host response to infection. Several factors influence the severity, clinical manifestations and progression of sepsis, such as immunological heterogeneity and dynamic regulation of cell signaling pathways. The evolution of patients depends on timely treatment, clinical scoring scales allow to know the estimated mortality. OBJECTIVE. To evaluate mortality in the intensive care unit; to establish the management and usefulness of applying bundlers to prevent progression to dysfunction, multiorgan failure and death. METHODOLOGY. Systematic review type research modality. A bibliographic search was carried out in databases such as Google Scholar, Mendeley, ScienceDirect, Pubmed, journals such as New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. We obtained the guidelines "Surviving Sepsis" update 2021, 3 international guidelines, 10 observational studies, 2 multicenter studies, 5 randomized trials, 6 systemic reviews, 5 meta-analyses, 1 clinical case report, 4 articles with expert opinions and updates on the subject of sepsis mortality in ICU with a total of 36 scientific articles. RESULTS. The mortality of sepsis in the intensive care unit, was lower in the oncological hospital of Guayaquil, followed by Australia, Germany, Quito, France, United States of America and Vietnam, The highest mortality is observed in patients with connective tissue diseases. DISCUSSION. The application of bundlers in sepsis is associated with better survival and shorter days of hospital stay. CONCLUSIONS. The SOFA, APACHE II and SAPS II scales help to predict mortality efficiently in the early detection and treatment of patients with acute and high-risk disease.

Prevalencia de Complicaciones clínicas y quirúrgicas en el postrasplante renal inmediato y su impacto a corto plazo en la función renal / Prevalence of clinical and surgical complications in immediate post-renal transplantation and their short-term impact on renal function

INTRODUCCIÓN. La enfermedad renal crónica es definida como la pérdida progresiva, permanente e irreversible de la función renal, uno de los tratamientos es el trasplante renal el mismo que aumenta la calidad de vida de los pacientes que presentan esta patología, sin embargo, a pesar de ser uno de las mejores terapias no está exento de complicaciones especialmente las que se presentan posterior al acto quirúrgico ya que afectan al buen funcionamiento del injerto y afecta la supervivencia del mismo. OBJETIVO. Determinar la prevalencia de complicaciones clínicas y quirúrgicas en el postrasplante renal inmediato con el fin de identificar las principales complicaciones que ocasionan mayor deterioro en la función renal a corto plazo. MATERIAL Y MÉTODOS. Estudio Observacional descriptivo transversal, de pacientes trasplantados que se encuentran en seguimiento desde enero del 2015 hasta diciembre del 2018 en el servicio de Trasplante renal del Hospital de Especialidades Carlos Andrade Marín. La muestra será los 211 pacientes trasplantados de donante cadavérico. Los análisis se realizaron con el paquete estadístico IBM SPSS versión 25, para lo cual se empleó estadísticas descriptivas, utilizando tablas y representando los valores absolutos y relativos de las variables cualitativas, así como medidas de tendencia central y de variabilidad para las variables cuantitativas. RESULTADOS. Se estudiaron 193 pacientes trasplantados de los cuales el 49.66% tuvieron complicaciones, de los mismos el 33.16% fueron complicaciones clínicas y 16,5% complicaciones quirúrgicas; de las clínicas la infección de tracto urinario fueron las más prevalentes con 15%, seguida por el rechazo agudo 6,7%, las infecciones por virus poliomavirus BK fueron un porcentaje de 6,2%, la necrosis tubular aguda el 3,16% terminando con el rechazo hiperagudo en el 1,5% y la toxicidad por calcineurínicos 1,04%. Mientras tanto las complicaciones quirúrgicas las urológicas son las más prevalentes 8,8% seguida por las colecciones liquidas con el 6,74% finalmente la trombosis vascular con el 1,04%. CONCLUSIONES. Las complicaciones más prevalentes son las clínicas vs las quirúrgicas, afectando de igual forma la función renal al año sin diferencia estadísticamente significativa.

INTRODUCTION. Chronic kidney disease is defined as the progressive, permanent and irreversible loss of renal function, one of the treatments is renal transplantation, which increases the quality of life of patients with this pathology, however, despite being one of the best therapies, it is not free of complications, especially those that occur after surgery, since they affect the proper functioning of the graft and affect its survival. OBJECTIVE. To determine the prevalence of clinical and surgical complications in immediate post-renal transplantation in order to identify the main complications that cause greater deterioration in short-term renal function. MATERIAL AND METHODS. Cross-sectional descriptive observational study, of transplanted patients under follow-up from January 2015 to December 2018 in the Renal Transplant service of the Hospital de Especialidades Carlos Andrade Marín. The sample will be the 211 cadaveric donor transplanted patients. The analyses were performed with the IBM SPSS version 25 statistical package, for which descriptive statistics were used, using tables and representing the absolute and relative values of qualitative variables, as well as measures of central tendency and variability for quantitative variables. RESULTS. We studied 193 transplanted patients of whom 49.66% had complications, of which 33. Of the clinical complications, urinary tract infection was the most prevalent with 15%, followed by acute rejection 6.7%, polyomavirus BK infections were 6.2%, acute tubular necrosis 3.16%, ending with hyperacute rejection in 1.5% and calcineurin toxicity 1.04%. Meanwhile, urological surgical complications are the most prevalent 8.8% followed by liquid collections with 6.74% and finally vascular thrombosis with 1.04%. CONCLUSIONS. The most prevalent complications are clinical vs. surgical, affecting renal function at one year with no statistically significant difference.

Coriorretinopatia de Birdshot: relato de caso e perspectivas sobre o tratamento / Birdshot chorioretinopathy: a case report and perspectives on its treatment

RESUMO A coriorretinopatia de Birdshot é uma uveíte posterior bilateral crônica rara que acomete, preferencialmente, mulheres de meia-idade. O quadro clínico é composto de pouco ou nenhum processo inflamatório de segmento anterior, associado a vitreíte e lesões coriorretinianas ovoides branco-amareladas de característica hiperfluorescente na angiofluoresceinografia e hipofluorescente na angiografia com indocianina verde. O tratamento se dá por meio de corticoides e outras drogas imunossupressoras. Todavia, em alguns casos, a doença é refratária a tal terapêutica, sendo necessário lançar mão de outras drogas, como os agentes biológicos. O presente artigo busca relatar um caso de coriorretinopatia de Birdshot em ajuste de terapia imunossupressora que evoluiu com má resposta às drogas iniciais e bom controle após uso de imunobiológico e discutir as opções terapêuticas disponíveis atualmente.

ABSTRACT Birdshot chorioretinopathy is a rare chronic bilateral posterior uveitis that preferentially affects middle-aged women. The clinical picture is composed of little or no anterior segment inflammatory process, associated with vitritis and yellowish-white ovoid chorioretinal lesions with hyperfluorescent characteristics on fluorescein angiography and hypofluorescent characteristics on green indocyanine green angiography. Treatment is with corticosteroids and other immunosuppressive drugs. However, in some cases, the disease is refractory to such therapy, making it necessary to resort to other drugs such as biological agents. The present article seeks to report a case of Birdshot chorioretinopathy in an adjustment of immunosuppressive therapy that evolved with poor response to the initial drugs and good control after the use of immunobiologicals and discuss the currently available therapeutic options.

Drug-drug interactions of immunosuppressants and other drugs in kidney post-transplant recipients

Introduction: Immunosuppressants (ISS) are the most crucial tools used in the therapeutic regimens of transplant recipients. Nevertheless, these drugs are not the only ones adopted by patients; therefore, knowing the possible drug-drug interactions (DDIs) between immunosuppressants and other drugs commonly used in kidney transplant recipients is essential to ensure the effectiveness and safety of treatments. In this way, the objective is analyzing the DDIs between the immunosuppressants and other commonly used medications on kidney transplant adult recipients with active medical records undergoing post-transplant follow-up for 4.4 years (mean). Methods: First, we performed a cross-sectional study based on patients' records, in which the patient's profile and drugs used were examined, and after we analyzed DDIs by the Micromedex Drug Interactions® database. Results: We analyzed 176 patients with a mean age of 47.6(± 12.5); most were male (67.7%), and the majority received a kidney from a deceased donor (81.4%). Patients were exposed to 15.0 (± 5.4) different medicines after the transplantation, and 7.4 (± 4.0) of these medicines were simultaneous. After analyzing the DDIs according to the severity of interaction, documentation quality interaction effect, clinical management and probable interaction mechanism, the most frequent interaction was with tacrolimus, classified as moderate, and the 3 major causes of interaction occurred with azathioprine according to the Micromedex database. The primary medicines involved with immunosuppressant interactions were proton pump inhibitors, ranitidine, domperidone, amlodipine, enalapril, allopurinol, cyclobenzaprine, amitriptyline, fluoxetine, and ciprofloxacin. These DDIs' effects were related to, mainly, increase their immunosuppressant activity. Conclusion: Although the immunosuppressants analyzed lacked many clinical DDIs significance with other medicines, the healthcare team needs to monitor their DDIs' effects to prevent and minimize side effects in transplanted recipients.

Anemia aplásica: un nuevo reto farmacológico en la práctica clínica / Aplastic anemia: a new pharmacological challenge in clinical practice

Introducción: la anemia aplásica (AA) es una enfermedad poco frecuente, caracterizada por presentar una insuficiencia en la médula ósea y una pancitopenia, sin rastro de procesos mieloproliferativos o fibróticos. Objetivo: conocer los diversos tratamientos farmacológicos usados en la terapia inmunosupresora (IST) en la AA; adicionalmente, se profundizará en la respuesta de los pacientes frente a la IST y los mecanismos de acción de los fármacos utilizados. Metodología: se realizó una búsqueda sistemática en las bases de datos de literatura médica como PUBMED, British Medical Journal, New England Journal, entre otros. Se incluyeron artículos tanto en inglés como en español. Conclusiones: el manejo de la anemia aplásica continúa representando un reto para la medicina moderna; no obstante, se ha desarrollado un gran número de nuevas opciones terapéuticas para tratar a los pacientes.

Introduction: Aplastic anemia (AA) is a rare disease characterized by presenting bone marrow failure and pancytopenia, with no trace of myeloproliferative or fibrotic processes. Objective: To present the different pharmacological treatments used in immunosuppressive therapy (IST) in AA, in addition, the response of patients to IST and the mechanisms of action of the drugs used will be studied in depth. Methodology: A systematic search was carried out in medical literature databases such as PUBMED, British Medical Journal, New England Journal, among others. Articles in both English and Spanish were included. Conclusions: The management of aplastic anemia continues to represent a challenge for modern medicine; however, a large number of new therapeutic options have been developed to treat patients.

Value of Improved Mayo Endoscopic Score for evaluating treatment efficacy for active ulcerative colitis / 南方医科大学学报

OBJECTIVE@#To assess the value of Improved Mayo Endoscopic Score (IMES) for evaluation of treatment efficacy for active ulcerative colitis (UC).@*METHODS@#We retrospectively analyzed the clinical and endoscopic data of 103 patients diagnosed with active UC in Beijing Tsinghua Changgung Hospital from January, 2015 to December, 2020. The severity of endoscopic lesions was determined by Mayo Endoscopic Score and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and the area of the endoscopic lesions was evaluated based on the Montreal classification system. The IMES was established by combining the MES with the Montreal classification.@*RESULTS@#Univariate analysis suggested that young patients (<40 years old), patients with extensive disease type (E3), patients with high endoscopic scores (MES=3, UCEIS>4, and IMES>4), and patients receiving advanced drug therapy (with systemic hormones, immunosuppressants, immunomodulators, and biological agents, etc.) had lower clinical and endoscopic remission rates. COX survival analysis showed that IMES≤4 was an independent risk factor for clinical and endoscopic remission. ROC curve indicated that the predictive value of IMSE≤4 for clinical and endoscopic remission (AUC=0.7793 and 0.7095, respectively; P<0.01) was better than that of Montreal (AUC=0.7357 and 0.6847, respectively; P<0.01), MES=2 (AUC=0.6671 and 0.5929, respectively; P<0.01), and UCEIS≤4 (AUC=0.6823 and 0.6459, respectively; P<0.01); IMES=5 had a better predictive value for patients with active UC undergoing colectomy tham E3 and MES=3.@*CONCLUSION@#IMES has good value in evaluating treatment efficacy for active UC.

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.

Medical visit status and clinical features in patients with IgG4 related disease / 北京大学学报(医学版)

OBJECTIVE@#To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments.@*METHODS@#A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized.@*RESULTS@#A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%).@*CONCLUSION@#IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.

Comparison of clinical and immunological characteristics between primary Sjögren's syndrome patients with positive and negative anti-SSB antibody / 北京大学学报(医学版)

OBJECTIVE@#To analyze the differences of clinical manifestations and laboratory features between primary Sjögren's syndrome (pSS) patients with positive and negative anti-Sjögren's syndrome type B (SSB) antibody.@*METHODS@#The clinical data of pSS patients hospitalized in Department of Rheumato-logy and Immunology, Peking University Third Hospital were retrospectively analyzed to investigate the differences of clinical and laboratory features between anti-SSB positive and negative groups. The t test, Mann-Whitney U test, Chi-square test and Fisher's exact probability were used for analysis.@*RESULTS@#A total of 142 pSS patients were enrolled in this study, including 137 females and 5 males with a mean age of (54.8±13.3) years. The anti-SSB positive group included 44 patients accounting for 31.0% of the pSS patients. The anti-SSB positive pSS patients were younger at disease onset and at visit [age at visit: (50.9±14.5) years vs. (56.5±12.4) years; age at onset: (42.2±14.8) years vs. (49.5±15.3) years, P < 0.05]. The patients with anti-SSB positive more frequently presented with rash (29.5% vs. 14.3%, P < 0.05), enlargement of parotid glands (27.3% vs. 8.2%, P < 0.05), renal tubular acidosis (15.9% vs. 4.2%, P < 0.05), immune thrombocytopenia (9.1% vs. 1.0%, P < 0.05), rheumatoid factor (RF) positive (85.0% vs. 49.4%, P < 0.05), higher RF and antinuclear antibody (ANA) titers (median: 89.8 IU/mL vs. 20.5 IU/mL; median: 320 vs. 160, P < 0.05), anti-Sjögren's syndrome type A (SSA) antibody positive (97.7% vs. 64.3%, P < 0.05), elevation of γ globulin (71.4% vs. 38.5%, P < 0.05), higher levels of IgG (median: 21.0 g/L vs. 15.6 g/L, P < 0.05), higher proportions of CD3-CD19+ cells [(21.0±11.9)% vs. (13.7±9.6)%, P < 0.05] and lower proportions of CD3+ cells [(67.2±14.4)% vs. (76.6%±13.1)%, P < 0.05] than those negative. However, the anti-SSB positive group was less likely to show anti-mitochondrial antibodies (AMA)-M2 positivity (10.5% vs. 35.6%, P < 0.05). Glucocorticoids (90.9% vs. 73.5%, P < 0.05) and immunosuppressants (54.5% vs. 36.7%, P < 0.05) were more frequently used in anti-SSB positive pSS patients than those negative.@*CONCLUSION@#The anti-SSB positive pSS patients were younger at disease onset while more frequently presenting with various symptoms, higher levels of other antibodies and activation of B cells than those negative. Glucocorticoids and immunosuppressants were more frequently used, indicating that anti-SSB positive group presented with a more severe clinal phenotype.

Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome / 中华儿科杂志

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.

Advances of the novel immunosuppressant brasilicardin A / 生物工程学报

Brasilicardin A (BraA) is a natural diterpene glycoside isolated from the pathogenic actinomycete Nocardia brasiliensis IFM 0406 with highly potent immunosuppressive activity (IC50=0.057 μg/mL). BraA potently inhibits the uptake of amino acids that are substrates for amino acid transport system L of T cells, which is different from the existing clinical immunosuppressants. BraA is more potent in a mouse mixed lymphocyte reaction and less toxic against various human cell lines compared with the known clinical immunosuppressants, such as cyclosporin A, ascomycin and tacrolimus. Therefore, BraA attracted more attention as a new promising immunosuppressant. However, the development of this promising immunosuppressant as drug for medical use is so far hindered because BraA has the unusual and synthetically challenging skeleton and shows the low-yield production in the natural pathogenic producer. This review introduces the molecular structure of BraA, its activity, mechanism of action, chemical synthesis of BraA analogs, heterologous expression of gene cluster, and an application of combining microbial and chemical synthesis for production of BraA, with the aim to facilitate the efficient production of BraA and its analogs.

Biosynthesis of immunosuppressant tacrolimus: a review / 生物工程学报

Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.

Evidence-based recommendations for the treatment of rheumatic and immunologic diseases with calcineurin inhibitors: a consensus statement / 中华内科杂志

Calcineurin inhibitors (CNI), including oral cyclosporin A and tacrolimus, are intensive immunosuppressants that are extensively used in the treatment of rheumatic and immunologic diseases in China. CNI selectively inhibit the activation and proliferation of T lymphocytes and the transcription of cytokines [such as tumor necrosis factor-α, interleukin (IL)-6, and IL-17] through inhibiting the activation of calcineurin in cells and reducing the release of IL-2. To standardize the use of CNI in the field of rheumatic and immunologic diseases, this consensus statement was developed by the National Clinical Research Center for Dermatologic and Immunologic Diseases (Peking Union Medical College Hospital), in conjunction with the Chinese Association of Rheumatology and Immunology Physicians, the Chinese Research Hospital Association, the Rheumatology and Immunology Professional Committee, and the Chinese Association of Rehabilitation Medicine. The 2011 Oxford Centre for Evidence-Based Medicine Levels of Evidence was used to rate the quality of the evidence and the strength of the recommendations, and the RIGHT (Reporting Items for practice Guidelines in HealThcare) checklist was followed to report the consensus. The consensus offers recommendations addressing nine clinical challenges to Chinese clinicians. The primary objective of this consensus is to deliver scientific and detailed guidance on CNI for Chinese clinicians, and to improve the quality of patient-centered medical services.

Hemosiderosis pulmonar idiopática, caso clínico en México. Importancia de un diagnóstico y tratamiento oportuno / Idiopathic pulmonary hemosiderosis, clinical case in Mexico. The relevance of performed an early diagnosis and treatment

La hemosiderosis pulmonar idiopática (HPI) es una patología poco frecuente; su distribución geográfica, su incidencia y prevalencia se desconocen de manera exacta a nivel mundial. Tiene una fuerte asociación con condiciones autoinmunes y una adecuada respuesta al tratamiento inmunosupresor. A pesar de ser una patología grave, presenta una tasa de morbilidad y mortalidad mediana, siempre que se realice un diagnóstico y tratamiento precoz. Se presenta el caso clínico de una paciente femenina con diagnóstico de HPI quien cursó con la triada clásica de esta enfermedad: hemoptisis, anemia ferropénica e infiltrados pulmonares difusos. Se descartaron otras causas de hemorragia pulmonar difusa y se realizó el diagnóstico por biopsia pulmonar. Se trató con esteroides sistémicos e inhalados y azatioprina. Tras casi 2 años después del diagnóstico, estando sin tratamiento por 3 meses, presentó una exacerbación con hemorragia pulmonar masiva ocasionando el fallecimiento de la paciente.

Idiopathic pulmonary hemosiderosis (IPH) is a rare pathology; its geographic distribution, incidence and prevalence are not accurately known worldwide. It has a strong association with autoimmune conditions and has an adequate response to immunosuppressive treatment. Despite being a serious pathology, it has a medium morbidity and mortality rate, provided that early diagnosis and treatment is performed. We present the clinical case of a female patient diagnosed with IPH who presented with the classic triad of this disease: hemoptysis, iron deficiency anemia and diffuse pulmonary infiltrates. Other causes of diffuse pulmonary hemorrhage were ruled out and the diagnosis was made by lung biopsy. She was managed with systemic and inhaled steroids and azathioprine. After almost 2 years before the diagnosis, being without treatment for 3 month she had a massive pulmonary hemorrhage, causing the death of the patient.

Approaches in the treatment of perianal fistula in Crohn disease

Perianal fistula is a common complication of Crohn disease, and it is a great burden on the life and psychology of patients, but its treatment is still a difficult problem to face. In recent years, progress in the treatment of Crohn disease has progressed rapidly due to the advent of biological agents, but there has been a lack of research on perianal fistula in Crohn disease, and the direction of research has been scattered; therefore, the author reviews the traditional treatment of perianal fistula in Crohn disease in the context of the available literature and discusses emerging and potential therapeutic approaches. (AU)

Estado nutricional de pacientes submetidos ao transplante renal / Nutritional status of patients submitted to kidney transplantation

No período de pós Transplante Renal (TxR) o uso de imunossupressores é indicado. Seu uso crônico se associa a alterações endocrinometabólicas e do estado nutricional. Objetivo: Avaliar o estado nutricional de pacientes com Doenças Renais Crônicas (DRC) submetidos ao transplante renal. Método: Trata-se de um estudo transversal, realizado com pessoas que vivem com a DRC, submetidas ao TxR, no período mínimo de 6 (seis) meses. Coletou-se dados socioeconômicos, demográficos, antecedentes clínicos e antropométricos. Feita análise estatística dos dados e determinada a média e desvio padrão das variáveis numéricas. Verificou-se a normalidade dos dados pelo teste de Shapiro Wilk. Para variáveis não-paramétricas, foi aplicado teste de U-Mann-Whitney. Para variáveis categóricas, foi realizada análise descritiva. A comparação foi feita por Qui-quadrado de Pearson ou teste Exato de Fisher. Foi adotado p<0,05. Resultados: Ao avaliar 52 pacientes observou-se interação significativa entre o sexo feminino e o ganho de peso (p=0,02). A eutrofia foi prevalente segundo o Índice de massa corporal IMC (48,08%), entretanto, a adequação da CB, CMB e AMBC apontou relevantes percentuais de desnutrição. Aumento da incidência de diabetes (5,77% vs 30,77%) e de dislipidemia (3,85% vs 17,31%) no período pós TxR. Conclusão: O ganho de peso se associou significativamente ao sexo feminino. Verificou-se que mesmo diante da prevalência de eutrofia ao avaliar o IMC, a desnutrição foi presente ao se classificar as adequações das circunferências corporais

In the period after Renal Transplantation (KTx) the use of immunosuppressants is indicated, their chronic use is associated with endocrine-metabolic alterations and nutritional status. Objective: Evaluate the nutritional status of patients with Chronic Kidney Diseases (CKD) after kidney transplantation. Method: This is a cross-sectional study, carried out with people living with CKD, submitted to KTx, for a minimum period of 6 (six) months. Data on socioeconomic, demographic, clinical and anthropometric background were collected. Statistical analysis of the data was performed and the mean and standard deviation of numerical variables were determined. Data normality was verified by the Shapiro Wilk test. For non-parametric variables, U-Mann-Whitney´s test was applied. For categorical variables, descriptive analysis was performed. Comparison was performed using Pearson's chi-square or Fisher's test. The results were discussed at the 5% level of significance. Results: When assessing 52 patients, a significant interaction was observed between female gender and weight gain. (p=0,02). Eutrophy was prevalent according to BMI(48,08%) However, the adequacy of the MAC, MAMC and AMA presented relevant percentages of malnutrition. Increased incidence of diabetes (5,77% vs 30,77%) and dyslipidemia (3,85% vs 17,31%) in the period after KTx. Conclusion: The weight gain was significantly associated with female gender. It was found that even in the face of the prevalence of eutrophy when assessing BMI, malnutrition was present when classifying the adequacy of body circumferences