ObjectiveTo summarize progress of immune response in severe acute pancreatitis (SAP) and to provide a basis for appropriate immunotheraphy.MethodThe relevant literatures about the effect of immune response in the SAP with infectious complications in recent years were reviewed.ResultsThe inflammatory cascade reaction occurred in the early stage of SAP. Subsequently, the compensatory anti-inflammatory response syndrome (CARS) arised and immune response of the organism was suppressed. At this stage, the rate of infection was higher than before.ConclusionsCARS is one of major reasons in SAP with infectious complications. At present, fluid infusion, fasting, parenteral nutrition and like are major therapies in SAP. If corresponding immunotherapy could be carried out according to immune mechanism of SAP infection, that is, early appropriate immunosuppressive therapy and dynamic monitoring of body’s immune system state should be performed, when it is found that immunosuppression is present, appropriate immunostimulus therapy will be possible to reduce mortality of SAP and improve its prognosis.
Objective To explore the effects of several immunosuppressants on the cell numbers of cultured rat macrophages and Schwann’s cells. Methods The macrophages and Schwann’s cells were cultured from the newborn Wistar rats. Different concentrations of methylprednisolone(10-3, 10－4,10－6 and 10－8 mol/L), CsA(10－5, 10－6, 10－7 and 10－8 mol/L) and FK506(10-6, 10－7, 10－8 and 10－9 mol/L) were administrated to the cells, while control group was given no drugs. Twentyfour, 48 and 72 hours after administration, the cells from different concentrations were measured with MTT methods respectively. Theresults were compared and analyzed statistically. Results Only high concentration methylprednisolone (10-4 mol/L) and a certain range of concentrations of CsA (10-6，10-7 and 10-8 mol/L) and FK506 (10-7,10-8 and 10-9 mol/L) can provide protection to culturedrat macrophages. Under most concentrations, CsA and FK506 had no effects onthe cell number of cultured rat Schwann’s cell. Only with high concentration CsA (10-5 mol/L) and methylprednisolone (10-3 mol/L) could significantly decreased the cell number of Schwann’s cell. Long time (72 hours) and low dosage (10-8 mol/L) administration of methylprednisolone could significantlyprotect Schwann’s cell. Conclusion High concentration methylprednisolone and some certain concentration CsA and FK506 can protect cultured rat macrophages. But high concentration CsA and methylprednisolone prohibit the proliferation of Schwann’s cells. Only long time and low dosage methylprednisolonecan protect cultured rat Schwann’s cells.
Human lymphocyte function-associated antigen 3 (hLFA3) has been identified as an important T cell accessory molecule. Rhesus monkeys (Macaca mulatta) have been widely used as animal models for human immune disorders. Due to the species-specificity of immune system, it is necessary to study M. mulatta LFA3 (mmLFA3). In this study, the gene encoding mmLFA3 CD2-binding domain (mmLFA3Sh) was amplified by polymerase chain reaction (PCR) and genetically fused to human IgG1 Fc fragment in pPIC9K to construct the expression plasmid pPIC9K-mmLFA3Sh-Ig. Approximately 3-4 mg mmLFA3Sh-Ig protein was recovered from 1 L of inductive media, and mmLFA3Sh-Ig produced by the P. pastoris can bind to the CD2 positive cells, and suppress the monkey and human lymphocytes proliferation induced by Con A and alloantigen in a dose-dependent manner. These results suggested that mmLFA3Sh-Ig might be used as a novel tool for pathogenesis and experimental immunotherapy of Rhesus monkey immune disorders.
Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the influence factors, as well as the early intervention measures. It is shown that multiple drugs, including chemotherapy drugs, immunotherapy drugs, directly acting antivirals, cell therapy, etc., can induce HBV-R by affecting host immunity or directly activating HBV transcription factors. HBV-R could cause severe liver damage, even interruption of treatment of original diseases, affecting the prognosis of patients. Through precisely identifying risk drugs, monitoring the influence factors, and prescribing preventive anti-HBV regimen if necessary, the incidence of HBV-R can be significantly reduced. It is also suggested that clinical physicians should not only pay attention to the early identification and intervention of HBV-R, but also further study the mechanism of HBV-R in depth, especially the underlying mechanism between host, HBV and risk factors. This will help to promote the discovery of more valuable markers for risk prediction and targets for early intervention, and to further reduce the risk of HBV-R and improve the prognosis of patients.
Objective To summarize the significance of CYP3A5 in individualized immunosuppressive treatment with tacrolimus (FK506) after liver transplantation. Methods Relevant literatures about the effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in liver transplant recipients, which were published recently domestic and abroad, were reviewed and analyzed. Results Tacrolimus was used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variation in pharmacokinetics made it difficultly to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters influenced the plasma concentration of tacrolimus. CYP3A5 genotype had an effect on the tacrolimus dose requirement in liver transplant recipients.Conclusion Genotyping for CYP3A5 may help optimal individualization of immunosuppressive drug therapy for patients undergoing liver transplantation
ObjectiveTo evaluate the effectiveness of preoperative immunosuppressive therapy combined with surgical intervention. MethodsA retrospective study was conducted on Behçet's disease patients who underwent cardiac surgery at Guangdong Provincial People's Hospital from 2012 to 2021. Patients were divided into immunosuppressive group and non-immunosuppressive group based on whether they received immunosuppressive therapy before surgery. The complications and long-term survival rates of the two groups were analyzed. ResultsA total of 28 patients were included, among which 2 patients underwent reoperation, a total of 30 surgeries were performed, including 16 males (53.3%), and the confirmed age was 37 (31, 45) years old. There were 15 surgeries in the immunosuppressive group and 15 surgeries in the non-immunosuppressive group. Compared with the non-immunosuppressive group, the incidence of complications during hospitalization in the immunosuppressive group was lower (13.3% vs. 53.3%, P=0.008). One patient died in hospital, and the rest were discharged and followed up, with a median follow-up time of 38.7 (15.1, 57.3) months, and there was no statistically significant difference in long-term survival rate between the two groups (26.7% vs. 6.7%, P=0.158). There was no statistically significant difference in the cumulative incidence of complications one month (20% vs. 53%, P=0.058) and one year (27% vs. 60%, P=0.065) after surgery between the immunosuppressive group and the non-immunosuppressive group, but there was a statistically significant difference in the cumulative incidence of complications three years after surgery (47% vs. 92%, P=0.002). ConclusionSurgical treatment can save lives in Behçet's disease patients with cardiovascular diseases, but the incidence of postoperative complications is high. Timely use of immunosuppressants before cardiovascular surgery can reduce the incidence of postoperative complications.
The corticosteroids are the firstline therapeutical agents for noninfectious uveitis patients, but systemic corticosteroids are ineffective for some chronic or recurrent patients, and have many long term usagerelated side effects; these patients may need treatment of immunosuppressive agents and/or biologic agents. However, the mechanism, indication, efficacy and sideeffects of each type of the immunosuppressive agents or biologic agents are not identical. In clinical practice, we should use different and sensitive immunosuppressive agents or biologic agents for different types of uveitis, and watch their efficacy and toxic effects closely. In order to improve the effectiveness of the treatment, the classification, efficacy and existing concerns of commonly used uveitis drugs need to be further clarified.
OBJECTIVE To study the immunosuppressive effect of combined therapy with FK506 and RS-61443 in rat limb allotransplantation. METHODS: A total of 101 male SD rats were randomly divided into seven groups and used as recipients, and 101 Wistar rats were used as donors. All SD rats were performed limb allotransplantation without using immunosuppressants in control group. In experimental groups (Groups 1-6), the recipients were immunosuppressed with various dosages of FK506, RS-61443 or FK506 + RS61443, after transplantation for 5 weeks. To evaluate the results, we observed circulation of the transplanted limb, the mean rejection time, the histologic grading of skin rejection of limb grafts and the survival time of limb grafts. RESULTS: The control group showed rejection signs (edema and erythema of the skin) after a mean time of 3.36 +/- 1.15 days, and the mean survival time of the allografts was only 7.00 +/- 0.78 days. In the groups only using FK506 or RS-61443, the survival time were prolonged to varying degrees, but rejection occurred even in the period of using drug. As dosage increased, the rejection could not be prevented and the damage to liver and kidney could be induced. In the group using FK506 in combination with RS-61443, only skin and muscle of limb allografts showed slight rejection sign, function of liver and kidney was not obviously affected, the mean survival time of limb allografts was prolonged to 58.76 +/- 6.81 days. CONCLUSIONS: A combination of FK506 and RS-61443 is a more potent immunosuppressive agent than FK506 oro RS-61443 in preventing the rejection of limb allografts, and it can obviously prolong the survival time of limb allografts.
ObjectiveTo investigate the diagnosis, clinical features, treatment and outcome of pure red cell aplasia (PRCA) caused by human parvovirus B19 (HPV-B19) infection in kidney recipients. Method The clinical courses of six patients with PRCA caused by HPV-B19 infection after renal transplantation in West China Hospital between May 2018 and April 2019 were retrospectively investigated. Results The six patients showed obvious anemia symptoms, lacking rash, joint pain and other clinical symptoms of viral infection. The hemoglobin level of five patients got totally remission from a course of intravenous immunoglobulin (IVIG) treatment, and anemia symptoms like fatigue, weakness got notable improvement. One patient had no improvement after two courses of IVIG treatment, and his anemia was significantly improved after the third IVIG course combined with immunosuppressant conversion(from tacrolimus to cyclosporine), and one patient with recurrence accepted a repeated course of IVIG treatment and obtained remission of severe anemia again. The median time of reticulocyte firstly rose to above 0.084×1012/L from the day of IVIG treatment ended was 3.50 (1.25, 5.00) days, and the median time required for a 30 g/L increase in hemoglobin to the end of IVIG treatment was 16.00 (9.25, 31.25) days. No serious adverse reactions occurred and all patients had stable graft function. Conclusions The main clinical manifestations of PRCA caused by HPV-B19 infection after kidney transplantation are anemia symptoms, lacking other clinical symptoms of viral infection. HPV-B19 DNA detection combined with blood routine examination, reticulocyte count and bone marrow cytology (or none) can diagnose HPV-B19 infection. High dose of IVIG is effective and safe, and a repeated course is still effective when the infection recurs. For refractory PRCA that IVIG monotherapy fail, a combination with conversion from tacrolimus to cyclosporine can effectively improve the anemia without graft dysfunction.