Pemphigus is a life-threatening autoimmune blistering disease affecting the skin and mucosa. Patients with severe pemphigus require long-term treatment with corticosteroids and other immunosuppressive drugs, which can lead to serious adverse events. Rituximab, a monoclonal antibody directed against the CD20 antigen of B lymphocytes, has been demonstrated to be effective in recalcitrant and life-threatening pemphigus.
Antibodies, Monoclonal, Murine-Derived ; adverse effects ; therapeutic use ; Antigens, CD20 ; immunology ; Humans ; Pemphigus ; therapy ; Rituximab

Inhibitors of tumor necrosis factor-alpha (TNF-alpha) have been approved for treating rheumatoid arthritis. As one of the biological response modifiers, etanercept has also been used in the treatment of psoriatic arthritis and inflammatory bowel disease. While etanercept is effective, certain infectious complications, such as tuberculosis, fungus, and cytomegalovirus, have been reported. We report the first Korean case of adenoviral pneumonia in a 55-year-old female who developed disseminated adenoviral infection following etanercept treatment, which resolved after anti-TNF-alpha discontinuation.
Risk Factors ; Recombinant Fusion Proteins/immunology ; Receptors, Tumor Necrosis Factor/immunology ; Middle Aged ; Immunoglobulin G/*adverse effects/immunology ; Immunocompromised Host/drug effects ; Humans ; Female ; Arthritis, Rheumatoid/*drug therapy ; Antirheumatic Agents/*adverse effects/immunology ; Antibodies, Monoclonal/*adverse effects/immunology ; Adenovirus Infections, Human/*etiology/immunology

OBJECTIVETo investigate the safety and efficacy of basiliximab as induction agent in preventing early acute rejection post heart transplantation.

METHODSBasiliximab (20 mg, iv) was administered one hour before and 4 days post operation to patients (n = 47) underwent heart transplantation between June 2004 and Feb 2005 in our department. Intravenous methylprednisolone (500 mg at operation beginning and repeated immediately post operation, followed by 125 mg every 8 hours for the first day). Prednisone was then initiated at 1 mg.kg(-1).d(-1) tapered 10 mg every 3 days to 10 mg/d. Mycophenolate mofetil (MMF, 0.5 - 1.0 g twice daily) was also administered post intubation, oral Cyclosporine A (CsA, 3 to 6 mg.kg(-1).d(-1)) was prescribed after transplantation if serum creatinine was < 150 micromol/L. The dose of CsA was individually adjusted to achieve a target serum concentration of 180 - 300 ng/ml. Endomyocardial biopsies were performed 3 weeks (19.7 +/- 9.6) d post heart transplantation. Biopsy specimens were graded according to the standardized criteria of the International Society for Heart and Lung Transplantation (ISHLT). Echocardiograms were routinely performed weekly within the first 3 weeks post-operation.

RESULTSAll 47 consecutive patients [mean age (44.9 +/- 13.4) years, range 13 - 63 years, 38 men] survived the operation and the underlying diseases was idiopathic cardiomyopathy (42.5%), ischemic heart disease (25.5%), arrhythmogenic right ventricular cardiomyopathy (17.0%), hypertrophic cardiomyopathy (4.2%), heart tumor (4.25%), valve heart disease (2.1%), hypertensive cardiomyopathy (2.1%) and giant cell myocarditis (2.1%). There were 4 patients with pre-operation PRA > 10% and CDC was less than 5% in all patients. The grades of the acute rejection in biopsy specimens were as follow: Grade (G) 0 in 30 (63.8%), G IA in 11 (23.4%), G IB in 3 (6.3%) and GII in 3 (6.3%) patients. The average dose of MMF was (1.2 +/- 0.3) g/d. The initial time of receiving CsA was (3.4 +/- 2.1) day post operation. The average cumulative dose of CsA was (4.1 +/- 1.2) mg.kg(-1).d(-1) before endomyocardial biopsy. The average serum concentration of CsA was (237.0 +/- 76.2) ng/ml. Left ventricular ejection fraction assessed by echocardiogram was normal in all patients within the first 3 weeks. Five patients suffered from respiratory infections and recovered post antibiotic and symptomatic therapies.

CONCLUSIONBasiliximab as induction agent in combination with conventional triple immunosuppressive therapy is safe and effective in preventing acute rejection in Chinese cardiac transplantation receipts.

Adolescent ; Adult ; Antibodies, Monoclonal ; adverse effects ; therapeutic use ; Female ; Graft Rejection ; prevention & control ; Heart Transplantation ; adverse effects ; immunology ; Humans ; Male ; Middle Aged ; Recombinant Fusion Proteins ; adverse effects ; therapeutic use ; Young Adult

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

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

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

OBJECTIVETo investigate the effect and its mechanism of reducing graft-versus-host disease (GVHD) by in vitro blockade of CD(40)-CD(40)L pathway in vitro, the donor T lymphocytes cultured in vitro with anti-CD(40)L mAb were transfused in bone marrow transplantation (BMT) GVHD mouse model.

METHODSC57BL/6(H-2b) spleen T cells were isolated as responder cells, and BALB/c(H-2d) spleen cells as stimulator cells. They were cocultured with or without Anti-CD(40)L mAb as anti-CD(40)L mAb group and control group, respectively. At day 5, the mixed lymphocyte response (MLR)-culture cells mixed with bone marrow cells and transfused respectively into the TBI conditioned recipient mice. The mice were divided into two groups: group A, bone marrow cells (2 x 10(6)) and spleen T lymphocytes (2 x 10(6)) from MLR control group; group B, bone marrow cells (2 x 10(6)) and spleen T lymphocytes (2 x 10(6)) from MLR anti-CD(40)L mAb group. The GVHD incidence and hematopoietic reconstitution were observed. Peripheral blood sera and spleen cells of the recipients mice were harvested at scheduled time points for the measurement of cytokines and T cell immunophenotyping with flow cytometry.

RESULTSThe incidence of GVHD in group A was 100% (10/10), and in group B was 20% (2/10). The percentage of H-2D(b) positive cells in group B (n = 8) was (93.54 +/- 2.32)% at day 40 after transplantation. The levels of cytokines in serum from group B were significantly lower than those from group A (P < 0.05). The expressions of CD(4)(+), CD(8)(+), CD(4)(+)CD(25)(+), CD(8)(+)CD(25)(+), CD(4)(+)CD(69)(+), CD(8)(+)CD(69)(+) and CD(4)(+)CD(40)L(+) were lower in group B than in group A (P < 0.05). The expressions of CD(8)(+)CD(40)L(+) and CD(4)(+)CD(45)RA(+) were similar in the two groups (P > 0.05).

CONCLUSIONBlockade of CD(40)-CD(40)L interaction in vitro could induce immune tolerance in vivo, reduce aGVHD in aGVHD mice model and form chimerism, which was mediated by inhibiting the Th1 and Th2 cytokines production, inducing tolerance of CD(4)(+) and CD(8)(+) cells to alloantigens. The obstruction of T cells activation after tolerance happened mainly at the early and mature phase of T cells activation. These provided the experimental basis for the use of anti-CD(40)L mAb in the clinical transplantation to prevent aGVHD.

Animals ; Antibodies, Monoclonal ; therapeutic use ; Bone Marrow Transplantation ; adverse effects ; CD40 Antigens ; physiology ; CD40 Ligand ; immunology ; physiology ; Graft vs Host Disease ; prevention & control ; Interleukin-10 ; blood ; Interleukin-4 ; blood ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVE: To observe the effect of cyclosporine and simulect mono or combination therapy on cardiac allo-transplantation in rats. METHODS: Recipients with allografts were treated with different doses of cyclosporine and/or simulect after cardiac allo-transplantation. Graft survival time was observed; the histopathological examination of graft tissues was performed; and levels of serum IL-2 and IL-4 were determined. RESULTS: Mono or combination therapy with cyclosporine and/or simulect increased the survival of cardiac allografts. With the prolongation of survival time of the grafts, the rejection of grafts was moderated. The serum IL-2 level increased in acute rejected grafts; the serum IL-4 level increased evidently in long survival grafts. CONCLUSION Cyclosporine and simulect have an effect in the prolongation of cardiac allograft survival in rats, and the combination therapy shows an evident synergistic effect.
Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Basiliximab ; Combined Modality Therapy ; Cyclosporine ; pharmacology ; therapeutic use ; Female ; Graft Rejection ; immunology ; Heart Transplantation ; adverse effects ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Recombinant Fusion Proteins ; pharmacology ; therapeutic use