Fibrosis ; drug therapy ; metabolism ; Humans ; Immunosuppressive Agents ; therapeutic use ; Models, Biological ; Sirolimus ; therapeutic use

Deregulation of soluble apoptosis stimulating fragment (sFas) plays an important role in glomerulonephritis (GN). The study assed the influence of immunosuppressive treatment on serum and urine sFas in patients with proliferative (PGN) and non-proliferative (NPGN) GN, and evaluated the potential of sFas measurements in predicting outcomes. Eighty-four patients with GN (45 males and 39 females) were included. Serum concentration (ng/mL) and urinary excretion (ng/mg of urinary creatinine) of sFas were measured before and after the treatment. After 12 months of therapy with steroids and cyclophosphamide, patients were divided into two subgroups according to the treatment results: Responders (R) and Non-Responders (NR). The sFas urinary excretion was reduced after treatment in both PGN and NPGN (from 17.12 +/- 15 to 5.3 +/- 4.2, P = 0.008 and from 10.11 +/- 6.1 to 3.4 +/- 3.0, P = 0.039; respectively) whereas the sFas serum concentration remained unchanged. In PGN, pre-treatment urinary sFas concentration was significantly lower in the Responders than in Non-Responders (2.3 +/- 3.1 vs 19.4 +/- 14.1, P = 0.003), and was lower still than in both R (P = 0.044) and NR (P = 0.042) subgroups with NPGN. The immunosuppressive treatment reduced sFas urinary excretion in proliferative and non-proliferative GN and results suggest that the lower urinary sFas may be linked with favorable therapy outcomes in patients with PGN.
Adult ; Antigens, CD95/blood/*urine ; Cyclophosphamide/therapeutic use ; Female ; Glomerulonephritis/*drug therapy/metabolism/pathology ; Humans ; Immunosuppressive Agents/*therapeutic use ; Male ; Middle Aged ; Steroids/therapeutic use ; Treatment Outcome

OBJECTIVETo explore the therapeutic effect of Jiawu Mufangji Decoction (JMD) in treating rats with adjuvant arthritis (AA) and its mechanism.

METHODSAA model rats induced by Freund's complete adjuvant were treated with JMD by gastrogavage starting from 18 days after modeling. On the 39th day, body weight, spleen and thymus index, and swelling degree of paw of the AA rats were measured, pathological changes of the ankle joint tissue were observed using HE staining, and serum levels of interleukin-1beta (IL-1beta) and tumor necrosis factor a (TNF-alpha) were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTSJMD could relieve the symptoms of AA rats, decrease the paw swelling, improve the weight and spleen and thymus index, reduce the dropsy of joints and lymphocytes infiltration, inhibit the proliferation of synovium, and obviously lower the serum levels of interleukin-1beta and TNF-alpha.

CONCLUSIONThe therapeutic effect of JMD might be related to its action in down-regulating the serum levels of IL-1beta and tumor necrosis factor alpha.

Animals ; Arthritis, Experimental ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Immunosuppressive Agents ; therapeutic use ; Interleukin-1 ; blood ; Male ; Phytotherapy ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUNDAccording to the renal phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (iMN) could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN.

METHODSA total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence. Among these patients, 186 (80.5%) with complete baseline clinical data were used for further study. Urinary protein excretion, serum albumin, and creatinine were analyzed. For those patients with follow-up longer than 1 year, the relationship between PLA2R and response to immunosuppressants were analyzed. The t-test was used for parametric analysis and the Mann-Whitney U-test was used for nonparametric analysis. Categorical variables were described as frequencies or percentages, and the data were analyzed with Pearson's Chi-square test or Fisher's exact test.

RESULTSOf the 231 iMN patients, 189 showed renal detectable PLA2R expression (81.8%). The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated (n = 145) and non-PLA2R-associated iMN patients (n = 41). However, about 1/3 of the non-PLA2R-associated iMN had abnormal serological tests, significantly more common than PLA2R-associated iMN (31.7% vs. 8.3%, P = 0.000). The non-PLA2R-associated iMN had lower C4 levels compared with PLA2R-associated iMN (P = 0.004). The non-PLA2R-associated iMN patients also showed a better response to immunosuppressants (complete remission [CR] 42.9%; partial remission [PR] 14.3%) compared with PLA2R-associated iMN (CR 3.2%; PR 48.4%, P = 0.004) at the 3rd month.

CONCLUSIONSThere were no significant differences in serum creatinine, albumin, and urine protein excretion between PLA2R-associated and non-PLA2R-associated iMN, while the non-PLA2R-associated iMN patients showed more abnormal serological tests. The non-PLA2R-associated iMN seemed to respond more quickly to the immunosuppressive therapy compared with PLA2R-associated iMN.

Adult ; Autoantibodies ; metabolism ; Female ; Glomerulonephritis, Membranous ; drug therapy ; metabolism ; pathology ; urine ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, Phospholipase A2 ; metabolism ; Retrospective Studies

OBJECTIVETo evaluate the potential usefulness of a multivariable model, established mainly upon peripheral T-cell subsets, Th1/Th2, T-bet and GATA-3 gene expressions as well as TCM and Western medical diagnostic criteria, in predicting the selection of immunosuppressive therapy (IST) or androgens in treating patients with aplastic anemia (AA).

METHODSPeripheral blood T cell subsets in 85 patients with AA were serially analyzed by flow cytometry before and after treatment, and their T-bet and GATA-3 gene expressions were assessed meantime by Real-time PCR. Then analysis of Logistic regression equation and ROC curves were performed based on the cases responding to IST or androgens.

RESULTS(1) According to the logistic equation and ROC curve of SPSS, setting the false positive rate as 0.10, the P value was 0.832. When P> or =0.832, patients were judged in the immunosuppressive dominant state, IST should be applied; when P<0.832, it means patients in the bone marrow failure dominant state, androgens should be added. (2) A novel theory is raised by the above-mentioned analysis, which indicated that the genesis and development process of AA could be divided in 2 stages, the abnormal immune dominant stage and the bone marrow failure dominant stage. For treatment of patients in the two stages, IST and androgens is the preference respectively.

CONCLUSIONThe multivariable model could be used for indicating which stage the AA patient is in, the abnormal immune stage or the bone marrow failure stage, and thus to guide the proper selection of IST or androgens in clinical practice.

Adult ; Aged ; Androgens ; therapeutic use ; Anemia, Aplastic ; drug therapy ; immunology ; Cyclosporine ; therapeutic use ; Female ; GATA3 Transcription Factor ; metabolism ; Humans ; Immunosuppressive Agents ; therapeutic use ; Logistic Models ; Male ; Middle Aged ; T-Box Domain Proteins ; metabolism ; T-Lymphocyte Subsets ; immunology ; Young Adult

OBJECTIVE: To detect the correlation between survivin and rheumatoid arthritis (RA) to determine the possible mechanism of RA and multidrug resistance in refractory rheumatoid arthritis (RRA). METHODS: We collected 15 normal controls, 35 early untreated RA patients, 20 effectively treated RA patients and 25 RRA patients according to selection standard. The expression of survivin in the peripheral blood lymphocytes was detected by immunocytochemical method. RESULTS: There was significant difference in the survivin expression in the peripheral blood lymphocytes between the early untreated and normal control group (χ(2)=29.59, P<0.01). The survivin expression in the peripheral blood lymphocytes of effectively treated RA group slightly elevated, but had no significant difference with the normal control group (χ(2)=1.591, P>0.05). The survivin expression in the peripheral blood lymphocytes of the RRA group was significantly stronger than in the effectively treated RA group (χ(2)=24.35, P<0.01), and normal control group (χ(2)=26.53, P<0.01), with no significant difference compared with early untreated group (χ(2)=0.014,P>0.05). CONCLUSION Survivin has an influential role in the occurrence and development of rheumatism arthritis. Survivin might be involved in refractory multidrug resistance of RA and be one of the multidrug resistance mechanism of RRA.
Adult ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; metabolism ; Case-Control Studies ; Drug Resistance, Multiple ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Inhibitor of Apoptosis Proteins ; metabolism ; Lymphocytes ; metabolism ; Male ; Middle Aged ; Survivin ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of the combined therapy with leflunomide and methotrexate in the patients with juvenile rheumatoid arthritis (JRA).

METHODSForty patients with active polyarthritis JRA were divided into 2 groups. Group 1 (n = 21) received leflunomide tablet (1 mg/(kg x day) on days 1 - 3; then [(0.2 - 0.4) mg/kg per day] plus methotrexate (0.3 mg/kg i.v. every two weeks till clinical remission, then oral tablet 0.2 mg/kg weekly). Group 2 received the same doses of methotrexate in the same way. Permitted concomitant drugs included stable doses of NSAIDs and a low dose of prednisone during the course of treatments. The clinical assessments included the number of tender and swollen joints, tender articular index, swollen articular index, general articular function score, parents and physician's evaluation score, erythrocyte sedimentation rate, serum C-reactive protein and rheumatoid factor. Drug safety was assessed by observing the reaction of mucous membrane, skin, gastrointestinal tract, nervous system, hematologic changes, liver and renal function. Statistical comparison between two groups was performed by using analysis of variance, t test and chi(2) test.

RESULTSEfficacy and safety was assessed at 12th and 26th week. Average improvement rate of leflunomide plus methotrexate group at 12th week and 26th week was respectively 39.6% and 71.9%; while that of control group was 27.5% and 49.5%, i.e., there was significant difference between the two groups (P < 0.01). Average remission rate of leflunomide plus methotrexate group at 12th week and 26th week was respectively 4.76% and 38.10%; while that of control group (methotrexate only) was respectively 0, 0. The clinical improvement in the group treated with leflunomide plus methotrexate was significantly greater than control group (P < 0.01). There was no significant difference (9.5% v 5.3%) in occurrence rate of side effects between the two groups. Side effects included leucocytopenia and raised aminotransferase. They were mostly mild and tolerable.

CONCLUSIONThe effect of the leflunomide and methotrexate therapy in patients with active JRA was better than methotrexate alone. The combination therapy with leflunomide and methotrexate was safe and well tolerated.

Adolescent ; Arthritis, Juvenile ; drug therapy ; metabolism ; Child ; Child, Preschool ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Infant ; Isoxazoles ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Methotrexate ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome

This study was purpose to investigate the frequency of HLA-DRB1*15 expression in children with aplastic anemia (AA) and its relation to effect of immunosuppressive therapy. HLA-DR genotypes were detected by SSP-PCR in 40 patients with acquired aplastic anemia and 107 normal controls, and the expressions of HLA-DR gene in AA patients and normal controls were compared. 32 out of 40 patients were treated with immunosuppressive therapy, which included antilymphocyte globulin combining with cyclosporine or cyclosporine alone, the relation of HLA-DRB1*15 expression to efficacy of immunosuppressive therapy and relapse of AA was explored. The results showed that the mean age of the patients was 9.0 years with a ratio of male to female 1.5:1. The frequency of HLA-DRB1*15 genotype expression in patients with idiopathic aplastic anemia was 51.5% (17/33), which was markedly higher than that of healthy controls (20.6%, p<0.01). All of 7 patients with second acquired aplastic anemia showed negative expression of HLA-DRB1*15. The rates of all responses, including complete remission and partial remission (CR+PR), and CR to immunosuppressive therapy in 16 patients who bared HLA-DRB1*15 were 93.8% and 87.5% respectively, which were higher significantly than those of patients without bearing HLA-DRB1*15 (56.3% and 31.3%, p<0.01). Relapse occurred in 5 patients who bared HLA-DRB1*15 genotype. It is concluded that the frequency of HLA-DRB1*15 genotype expression in children with AA is significantly higher than that in normal controls, and the immunosuppressive therapy for patients bared HLA-DRB1*15 shows favourable effect with high incidence of complete remission.
Adolescent ; Anemia, Aplastic ; drug therapy ; genetics ; immunology ; Antilymphocyte Serum ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; therapeutic use ; Female ; Genotype ; HLA-DR Antigens ; metabolism ; HLA-DRB1 Chains ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male

BACKGROUNDLong-term use of steroid with large dosage might cause many adverse effects in kidney transplant patients; reducing steroid dosage to a low level for maintenance is helpful in avoiding the side-effects, but meanwhile, acute rejection may rise to be a main concern. The present research monitored the immune function changes and the incidence of acute rejection and infection after rapid steroid reduction to investigate the safety of this strategy.

METHODSA prospective trial was conducted, using tacrolimus and mycophenolate mofetil as the basic immunosuppressive regimen, in addition to antibody induction with basiliximab. Corticosteroid dosage was rapidly reduced to 10 mg/d seven days post-transplantation in the experimental group, and the standard corticosteroid therapy was employed in the control group. Patient immunity was monitored by the Immune Cell Function Assay pre- and two weeks post-transplantation. The incidence of acute rejection and infection were compared between the experimental and control group.

RESULTSComparison of intracellular adenosine triphosphate (iATP) values detected two weeks post-transplantation for the control group ((324 ± 45) ng/ml) and the experimental group ((345 ± 91) ng/ml) did not reveal a significant difference (P > 0.05). The incidence of acute rejection was analogous between groups (P > 0.05), while an increased incidence of infection was observed in the control group (53% (n = 16)) versus the experimental group (22% (n = 6), P < 0.05). Overall, recipients in the control group had longer and more recurrent infections than those in the experimental group (P < 0.05). Patients in the control group had a lower immune response ((235 ± 35) ng/ml) than those in the experimental group ((286 ± 16) ng/ml) when infection occurred (P < 0.05).

CONCLUSIONRapid reduction of steroid early after kidney transplantation does not lead to a significant rise in patient immunity. It is a safe and effective therapy for kidney transplant patients.

Adolescent ; Adrenal Cortex Hormones ; metabolism ; Adult ; Antibodies, Monoclonal ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Prospective Studies ; Recombinant Fusion Proteins ; therapeutic use ; Young Adult

Sphingosine-1-phosphate (S1P) is a lysophospholipid signaling molecule that regulates important biological functions in both intracellular and extracellular compartments. It interacts with five G protein-coupled receptors subtypes (S1PR(1-5)) to generate multiple downstream signaling. Activation of S1PR1 has been validated to be involved in the process of immune modulation. Fingolimod (FTY720), the novel S1PR1 agonist, has been approved for the treatment of multiple sclerosis in clinical trials. The study towards discovery of selective S1PR1 agonists has become hot spot for immunological diseases. This article summarized the research progress of S1PR1 agonists, emphasizing their structure types, structure-activity relationship and direction of development.
Animals ; Fingolimod Hydrochloride ; Humans ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Lysophospholipids ; physiology ; Multiple Sclerosis ; drug therapy ; Propylene Glycols ; pharmacology ; therapeutic use ; Receptors, Lysosphingolipid ; agonists ; classification ; metabolism ; physiology ; Sphingosine ; analogs & derivatives ; pharmacology ; physiology ; therapeutic use ; Structure-Activity Relationship