BACKGROUND/AIMS: Recurrent focal segmental glomerulosclerosis (FSGS) following renal transplantation is relatively common. However, the risk factors and optimal pretransplant treatment preventing recurrence of FSGS remain controversial. METHODS: We retrospectively reviewed 27 adult renal transplant recipients with FSGS over a period of 10 years. We first compared possible risk factors for FSGS recurrence between the recurrence and nonrecurrence groups. Then we evaluated the effect of pretransplant plasmapheresis (PP; n = 4) and PP with rituximab (PP + RTX; n = 5) on recurrence of FSGS after transplantation compared to control patients that were not treated with these modalities. RESULTS: There were seven recurrences in 27 patients (25.9%), but there were no significant differences in possible risk factors for FSGS recurrence between the two groups. Recurrence rates between patients with pretransplant PP or PP + RTX and control patients were not significantly different (22.2% vs. 27.7%, p > 0.05). There was also no significant difference in recurrence between the pretransplant PP and PP + RTX groups (25% vs. 20%, p > 0.05). CONCLUSIONS: Pretransplant PP or PP + RTX do not significantly decrease the recurrence of FSGS in adult renal transplant candidates.
Adult ; Antibodies, Monoclonal, Murine-Derived/*administration & dosage ; Female ; Glomerulosclerosis, Focal Segmental/diagnosis/immunology/*surgery ; Humans ; Immunosuppressive Agents/*administration & dosage ; *Kidney Transplantation/adverse effects ; Male ; Middle Aged ; *Plasmapheresis ; Recurrence ; Retrospective Studies ; Risk Factors ; Treatment Outcome

We report a case of cytomegalovirus (CMV) retinitis after intravitreal bevacizumab injection. A 61-year-old woman with diabetic macular edema developed dense vitritis and necrotizing retinitis 3 weeks after intravitreal bevacizumab injection. A diagnostic vitrectomy was performed. The undiluted vitreous sample acquired by vitrectomy was analyzed by polymerase chain reaction and culture. Polymerase chain reaction of the vitreous was positive for CMV DNA. Other laboratory results did not show evidence of other infectious retinitis and systemic immune dysfunction. Human immunodeficiency virus antibodies were also negative. After systemic administration of ganciclovir, retinitis has resolved and there has been no recurrence of retinitis during the follow-up period of 12 months. Ophthalmologists should be aware of potential risk for CMV retinitis after intravitreal bevacizumab injection.
Angiogenesis Inhibitors/administration & dosage/adverse effects ; Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects ; Cytomegalovirus/genetics ; Cytomegalovirus Retinitis/diagnosis/*etiology/immunology ; DNA, Viral/analysis ; Diagnosis, Differential ; Female ; Humans ; Immunocompetence/*drug effects ; Intravitreal Injections ; Macular Edema/diagnosis/*drug therapy ; Middle Aged ; Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A/antagonists & inhibitors

Adult ; Antibodies, Monoclonal ; pharmacology ; Bronchoalveolar Lavage Fluid ; cytology ; Cells, Cultured ; Cytokines ; biosynthesis ; blood ; secretion ; Fas Ligand Protein ; antagonists & inhibitors ; metabolism ; Humans ; Macrophages, Alveolar ; immunology ; metabolism ; Middle Aged ; Occupational Exposure ; analysis ; Signal Transduction ; Silicon Dioxide ; adverse effects ; Silicosis ; blood ; immunology ; fas Receptor ; antagonists & inhibitors ; metabolism

Liposoluble cape jasmine proteins were used to immunize BALB/C mice. Indirect ELISA was utilized to develop one monoclonal antibody by integrating SP2/0 cells and spleen cells from immunized BALB/C mice. The subclass of the monoclonal antibody was identified as IgG2b, with Kappa chain as its light chain. The ascite titer of 2H8 monoclonal antibody was 1:204 080. Western-blot analysis proved that 2H8 reacted with cape jasmine proteins to identify specific liposoluble protein with molecuar weight of around 58.5 kDa. Dot-ELISA was established with 2H8 ascites as the primary antibody, showing the minimum detectable amount of 19.5 ng. This study lays a foundation for the development of protein kits of Reduning injection.
Animals ; Antibodies, Monoclonal ; analysis ; immunology ; Antibody Specificity ; Drug Hypersensitivity ; immunology ; Drugs, Chinese Herbal ; adverse effects ; analysis ; Enzyme-Linked Immunosorbent Assay ; methods ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Plant Proteins ; analysis ; immunology ; Reagent Kits, Diagnostic

BACKGROUND/AIMS: The widespread use of cytotoxic chemotherapy and immunosuppressants has resulted in reactivation of hepatitis B virus (HBV) recently becoming an issue. Although rituximab (an anti-CD20 monoclonal antibody) has revolutionized the treatment of lymphoma, recent reports have suggested that rituximab therapy increases the risk of viral-mediated complications, and particularly HBV reactivation. This study analyzed real clinical practice data for rituximab-related HBV reactivation. METHODS: Between January 2005 and December 2011, 169 patients received treatment with rituximab. Screening status of the HBV infection and frequency of preemptive therapy were determined in these patients, and the clinical features of HBV reactivation were analyzed. RESULTS: Seventy-nine of the 169 patients with chronic or past HBV infection were selected for evaluation of HBV reactivation. Of the 90 patients who were excluded, 22 (13.0%) were not assessed for HBsAg and anti-HBc, and 14 (8.3%) were not assessed for anti-HBc due to seronegativity for HBsAg. The selected patients were divided into those with chronic HBV infection (n=12) and those with past HBV infection (n=67); six patients (7.6%) experienced HBV reactivation. Eight patients received preemptive therapy, but three patients (37.5%) underwent HBV reactivation. Although HBsAg seropositivity was an independent risk factor for HBV reactivation (P=0.038), of the six patients with HBV reactivation, two (33.3%) had past HBV infection and three (50%) died of liver failure. CONCLUSIONS: The findings of this study demonstrate that adherence to guidelines for screening and preemptive therapy for HBV reactivation was negligent among the included cohort. Attention should be paid to HBV reactivation in patients with past as well as chronic HBV infection during and after rituximab therapy.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies/blood ; Antibodies, Monoclonal, Murine-Derived/*adverse effects/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Child ; Child, Preschool ; Hepatitis B/etiology/mortality/virology ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*physiology ; Humans ; Lymphoma/*drug therapy ; Middle Aged ; Odds Ratio ; Retrospective Studies ; Risk Factors ; *Virus Activation ; Young Adult

OBJECTIVETo analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE).

METHODThe diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria: age ≤ 16 years, number of important organs involved > 1, SLEDAI score > 10 points and poor response to conventional immunosuppressive treatment. These patients received 2 doses of 375 mg/m(2) rituximab (RTX), 2 weeks apart. Clinical, laboratory findings and drug side effects were recorded at RTX initiation, 2 weeks, 1 month, 3, 6 and 12 months after infusion.

RESULTA total of 20 patients. Male to female ratio was 1:3, were enrolled. They were 5-16 years old. The course of disease was (3.0 ± 2.5) years (range: 1 month-7 years), patients were followed up for 12 - 36 months [median: (27.0 ± 7.8) months]. Delirium and cognitive disorders were significantly improved in 10 cases of lupus encephalopathy after 1 month. Lupus nephritis in children were eased slowly, 14/15 patients with lupus nephritis were improved after 2-3 months. Four cases of lupus pneumonia were significantly improved within 1 month. Decreased blood cells counts were relieved at 1 month in 16/18 cases. Cellular immune function was assessed 2 weeks after application of anti-CD20 monoclonal antibody; we found B-cell clearance in 19 patients (95%). B lymphocyte count of 18 patients (90%) was restored within one year. SLEDAI score was reduced obviously. Dose of corticosteroid ranged from (45.0 ± 4.7) mg/m(2) before drug use to (12.0 ± 2.7) mg/m(2) 12 months later (P < 0.001). After the drug use, 5 patients had pneumonia within 6 months; 2 cases who suffered from aspergillus pneumonia and Pneumocystis carinii pneumonia respectively were severe. They accepted mechanical ventilation and anti-inflammatory support after being transferred to the intensive care unit, and their conditions improved at last. No death occurred. In 2 patients the disease recurred with B-cell recovery after 15 months and 18 months. Administration of another cycle of rituximab resulted in remission again in one case but not in the other.

CONCLUSIONAnti-CD20 monoclonal antibody is effective and safe in treatment of severe PSLE. But severe infections may occur in some cases. Focusing on prevention and early treatment can reduce the probability of adverse reactions.

Adolescent ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; adverse effects ; therapeutic use ; B-Lymphocytes ; drug effects ; immunology ; Biomarkers ; blood ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Follow-Up Studies ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Immunologic Factors ; administration & dosage ; adverse effects ; therapeutic use ; Lupus Erythematosus, Systemic ; complications ; drug therapy ; immunology ; Lupus Nephritis ; etiology ; pathology ; Male ; Pneumonia ; etiology ; pathology ; Prednisolone ; administration & dosage ; therapeutic use ; Rituximab ; Severity of Illness Index ; Treatment Outcome

OBJECTIVETo explore the effect of CD40 blockade in suppressing acute rejection of renal graft in rats.

METHODSWith Wistar rats as the donor and male SD rats as the recipients, rat models of acute renal graft rejection was established. The rat models were divided into therapy group and control group, and in the former group, CD40 ligand (CD40L) monoclonal antibody was injected daily for 4 consecutive days starting on the next day following kidney transplantation. On day 5 after the transplantation, the renal graft was harvested for histological examination, and graft rejection was evaluated semiquantitatively.

RESULTSThe mean semiquantitative score of the renal graft was 0.63∓0.52 in the therapy group, significantly lower than that of the control group (3.72∓1.48, P<0.05).

CONCLUSIONCD40L monoclonal antibody can inhibit acute renal graft in rats.

Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; CD40 Antigens ; antagonists & inhibitors ; immunology ; CD40 Ligand ; immunology ; Female ; Graft Rejection ; drug therapy ; prevention & control ; Graft Survival ; drug effects ; Kidney Transplantation ; adverse effects ; Male ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar

BACKGROUNDThe number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients.

METHODSSeven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21-47 years). The duration of hemodialysis was 3-12 months, with a mean duration of 11 months. For 4 patients, this was the second transplant; the previous graft survival time was 2-11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25-37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg × kg(-1) × d(-1)) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m(2)) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery. Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored.

RESULTSNo patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post-surgery. Diagnosis of acute rejections was based on the clinical assessments and pathological biopsy results. According to the Banff 07 classification of renal allograft pathology, one of the patients was Ia and the other was IIa; the C4d staining was negative in both patients. One patient received methylprednisolone plus cyclophosphamide and the other received antithymocyte globulin (ATG) therapy, both leading to successful reversion of the acute rejection. All patients were discharged postoperatively and all had normal renal function during the 7th to 12th month follow-up. Pulmonary infection occurred in 1 patient 4 months after surgery and was successfully cured.

CONCLUSIONRituximab induction therapy can reduce the occurrence of postoperative humoral rejection in highly sensitized renal transplant recipients, suggesting that kidney transplantation may be safe and effective for these patients.

Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Female ; Graft Survival ; drug effects ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; adverse effects ; immunology ; methods ; Male ; Middle Aged ; Retrospective Studies ; Rituximab ; Young Adult

OBJECTIVEThe effect of chronic morphine treatment on the I(A) (transient outward K+ current) of prefrontal cortical neurons of newborn rat. On this basis, we use AGS3 antibody to inhibit the function of AGS3, for observing the impact of AGS3 on the I(A), thus further explore the mechanism of AGS3 protein in morphine addiction.

METHODSBy using whole-cell patch-clamp technique, I(A) was recorded. In the whole-cell configuration, observed the impact of morphine on the current density-voltage curve (I-V) of I(A) and the effect of AGS3 antibody with three different concentrations on the I(A) of morphine treated rat prefrontal cortical neurons.

RESULTSMorphine increased the I(A). When the test potential was + 55 mV, different concentrations of AGS3, 10(-3) microg/L, 10(-2) micdrog/L and 10(-1) microg/L acted on morphine treated rat prefrontal cortical neurons, the enhanced IA by morphine was inhibited.

CONCLUSIONMorphine increases the I(A), AGS3 protein may participate in signal transduction pathway involved with I(A).

Animals ; Animals, Newborn ; Antibodies, Monoclonal ; pharmacology ; Carrier Proteins ; immunology ; metabolism ; Female ; Male ; Morphine ; adverse effects ; Neurons ; metabolism ; Patch-Clamp Techniques ; Potassium Channels ; drug effects ; Prefrontal Cortex ; metabolism ; Rats ; Rats, Sprague-Dawley ; Substance-Related Disorders ; metabolism ; physiopathology

BACKGROUNDBlocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver transplantation.

METHODSThe orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase (AST), alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)-gamma in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope.

RESULTSIsotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver allografts, and a mean graft survival time (MST) of 10.9 days. Administration of anti 4-1BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-gamma. The histological grade of rejection on day 7 decreased and MST (17.3 days) increased substantially.

CONCLUSIONSThese results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.

4-1BB Ligand ; immunology ; Alanine Transaminase ; metabolism ; Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Aspartate Aminotransferases ; metabolism ; Bilirubin ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Graft Rejection ; immunology ; prevention & control ; Graft Survival ; drug effects ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Liver Transplantation ; adverse effects ; Male ; Rats ; Rats, Inbred Lew