Recent reports have indicated that a significant number of immune complex glomerulonephritis (GN) cases are associated with antineutrophilic cytoplasmic antibody (ANCA). However, most of the reported cases were associated with underlying primary glomerular diseases. When primary glomerular diseases were not found, immune deposits tended to be non-specific and the level of ANCA is usually borderline. We report here upon a case of life-threatening pulmonary-renal syndrome manifested simultaneously with immune complex GN and myeloperoxidase (MPO)-ANCA seropositivity. A 29- year-old man was admitted with pulmonary hemorrhage and rapidly progressing renal dysfunction. On admission, ANCA revealed perinuclear staining with a titer of 1:160. The MPO-ANCA level was 59 IU by ELISA. Other serologic markers including ANA, anti-DS-DNA and anti-GBM Ab were negative. Renal biopsy showed cellular crescents in eight of 18 glomeruli. Immunofluorescence staining showed strong granular deposits of C3, C1q, IgG and IgM in the capillary loop and the mesangium. Electron microscopy showed multifocal electron dense deposits scattered in the mesangium, paramesangium, and the subendothelial and subepithelial areas. The patient initially responded to steroid and cyclophosphamide. MPO-ANCA decreased to less than 10 IU. Twenty three days after hospital discharge, the patient was re-admitted urgently with fever, generalized papulonodular skin lesions, and a recurrence of massive pulmonary hemorrhage and renal dysfunction. He died from uncontrolled pulmonary hemorrhage and respiratory insufficiency. P-ANCA titer and MPO-ANCA level at the second admission were 1:320 and 82 U/ml respectively. Interestingly, relapse was shown to be triggered by varicella zoster infection.
Adult ; Antibodies, Antineutrophil Cytoplasmic/*blood ; Antigen-Antibody Complex/*metabolism ; Glomerulonephritis/*etiology ; Hemorrhage/complications ; Human ; Lung Diseases/blood/*complications ; Male ; Peroxidase/*blood

OBJECTIVETo study the mechanism of spontaneous rupture of hepatocellular carcinoma (HCC).

METHODSThe specimens of 30 patients with ruptured HCC and 30 patients with non-ruptured HCC were collected. Immunofluorescence, immunohistochemical and flow cytometry techniques were used to detect the phagocytosis of macrophages and the deposition of immune complex (IC) on vascular wall.

RESULTSIn this study, the poor function of macrophage phagocytosis was found in patients with ruptured HCC, which could results in the cumulating of IC and deposition on vascular wall. The IC, which composed of hepatitis B virus e1 antigen (HBeAg/1), complement C1q and immunoglobulins, was found deposited in the elastic membrane of arteries. Likely as a result of IC deposition, vascular injury occurs mainly in the small arteries where the deposition of IC was present. As the small arteries were the blood vessels with predominant injury, they would likely to be the ones to split and cause hemorrhage and rupture of HCC during vascular load increase.

CONCLUSIONSWe would conclude that the poor function of macrophage phagocytosis, which lead to the IC deposition and vascular injury may be the factors involved in the pathogenesis of ruptured HCC.

Adult ; Antigen-Antibody Complex ; metabolism ; Carcinoma, Hepatocellular ; immunology ; pathology ; Complement C1q ; metabolism ; Female ; Flow Cytometry ; Hepatitis B e Antigens ; metabolism ; Humans ; Immunoglobulins ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; immunology ; pathology ; Macrophages ; immunology ; Male ; Middle Aged ; Rupture, Spontaneous ; immunology

OBJECTIVETo study the regulation of Fc receptor expression by immune complexes (ICs) on neutrophils and U937 cells.

METHODSIgA ICs, IgG1 ICs, IgG2 ICs, IgG3 ICs, IgG4 ICs, and IgM ICs were incubated with neutrophils or U937 cells for 1 h. Then their surface Fc receptors were stained by anti-Fc gammaR I, anti-Fc gammaR II , anti-Fc gammaR III, and anti-Fc alphaR I monoclonal antibodies and analyzed by fluorescent activated cell sorting (FACS).

RESULTSIgG1 ICs and IgG3 ICs up-regulated Fc gammaR II and Fc gammaR III on U937 cells, Fc gammaR I and Fc alphaR I on neutrophils. Almost all ICs down-regulated Fc gammaR II on neutrophils.

CONCLUSIONSICs can regulate Fc receptor expression on neutrophils and U937 cells, among which IgG1 ICs and IgG3 ICs are most effective.

Antibodies, Anti-Idiotypic ; immunology ; Antibodies, Monoclonal ; pharmacology ; Antigen-Antibody Complex ; immunology ; metabolism ; Antigens, CD ; immunology ; Humans ; Immunoglobulin A ; classification ; immunology ; Immunoglobulin G ; chemistry ; classification ; immunology ; metabolism ; Neutrophils ; metabolism ; Receptors, Fc ; biosynthesis ; genetics ; Receptors, IgG ; immunology ; U937 Cells ; immunology

Circulating immune complexes (ClC) were detected by platelet aggregation test (PAT) in 40.0% of 45 diabetics and by polyethylene glycol precipitation-complement consumption test (PEG-CC test) in 30.6% of 36 diabetics as compared to 5% and 10% of 20 normal control subjects for each test. The prevalence of CIC in diabetics was significantly higher than in the normal controls (P < 0.05%). There were no correlations between the presence of ClC detected by PAT and the duration of the disease, insulin treatment, or diabetic complications. Thus multiple factors must contribute to the increase of ClC in diabetics. The role of these various factors needs to be studied.
Antigen-Antibody Complex/metabolism* ; Diabetes Mellitus/complications ; Diabetes Mellitus/immunology* ; Diabetes Mellitus, Insulin-Dependent/drug therapy ; Diabetes Mellitus, Insulin-Dependent/immunology ; Diabetes Mellitus, Non-Insulin-Dependent/immunology ; Human ; Insulin/therapeutic use ; Platelet Aggregation ; Time Factors

OBJECTIVETo observe the effect of Shenfu Injection (SFI) on erythrocyte immunity function of patients undergoing cardiopulmonary bypass (CPB).

METHODSTwenty patients scheduled for valve replacement were randomly assigned to two groups, i.e. , the SFI group and the control group, 10 in each. SFI 1 mL/kg was intravenously dripped before induction of anesthesia and SFI 1 mL/kg administered in priming solution in the SFI group, while only normal saline was given to those in the control group. Venous blood samples (5 mL) were collected before induction of anesthesia (T1), 30 min CPB (T2), immediate by the end of CPB (T3), and postoperative 24 h (T4) respectively in all groups. The levels of the rosette rate of RBC-C3b receptor (RBC-C3bRR), the rosette rate of RBC-immune complex (RBC-ICR), plasma malondialdehyde (MDA), free hemoglobin (FHB), and interleukin-6 (IL-6) were detected.

RESULTSThere was no significant difference in the levels of RBC-C3bRR, RBC-ICR, plasma MDA, FHB, and IL-6 at T1 in both groups (P > 0.05). RBC-C3bRR at the rest time points was lower in the two groups than before induction of anesthesia. There was no statistical difference in FHB or IL-6 between T4 and T1 in the SFI group. The levels of RBC-ICR, MDA, FHB, and IL-6 increased in the two groups more than before induction of anesthesia at T2-4 ( P < 0.05). Besides, the RBC-C3b RR was lower, and levels of RBC-ICR, MDA, FHB, and IL-6 higher in the control group than in the SFI group, showing significant difference (P <0.05).

CONCLUSIONSFI could decrease the generation of inflammatory mediators during CPB, improve the erythrocyte immune function of patients during CPB, and reduce the risk of postoperative infection.

Adult ; Antigen-Antibody Complex ; blood ; Cardiopulmonary Bypass ; Drugs, Chinese Herbal ; pharmacology ; Erythrocytes ; drug effects ; immunology ; Female ; Hemoglobins ; analysis ; Humans ; Injections ; Interleukin-6 ; blood ; Male ; Malondialdehyde ; blood ; Middle Aged ; Receptors, Complement 3b ; metabolism

BACKGROUNDTo establish an immune complex induced rat liver fibrosis model by intraperitoneal injection of human serum albumin (HSA).

METHODSMale Wistar rats, weighting 110-120 g, were sensitized with HSA by subcutaneous injections at different sites for 4 shots at intervals of 14, 10 and 10 days. Ten days after the fourth injection, the peritoneal booster dose of HSA was administrated to rats twice weekly for 8 weeks with an initial dose of 5 mg, and progressive increase to 20 mg. Liver biopsy was performed at the beginning of HSA booster, 15, 30, 60 days after HSA booster, and 30, 60, 90, 120 days after discontinuation of HSA booster, respectively. Liver samples were examined for histological changes and liver hydroxyproline (HyP) was measured by biochemical method. Fibrosis serum markers hyaluronate acid (HA) and laminin (LN) were determined by RIA method.

RESULTSAfter intraperitoneal administration of HSA, the degree of liver pathological changes, the liver Hyp content and serum HA and LN increased (P<0.05). The longer the HSA administrated, the higher the liver pathological change degree (P<0.05) and the levels of liver Hyp and serum HA (P<0.01). After discontinuation of HSA, the levels of serum HA and liver Hyp decreased significantly (P<0.01) but were still significantly higher than those in the controls (P<0.01). The liver fibrosis formation rate was 100% and the fibrosis lasted more than 120 days.

CONCLUSIONIntraperitoneal administration of HSA to make rat immune complex induced liver fibrosis model is convenient with high liver fibrosis formation rate and long fibrosis lasting time. The model may be used to evaluate the therapeutic effect of antifibrotic drugs.

Animals ; Antigen-Antibody Complex ; administration & dosage ; toxicity ; Disease Models, Animal ; Fibrosis ; Humans ; Hyaluronic Acid ; metabolism ; Hydroxyproline ; metabolism ; Injections, Intraperitoneal ; Laminin ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; pathology ; Male ; Rats ; Rats, Wistar ; Serum Albumin ; administration & dosage ; toxicity

Astragalus heteropolysaccharides (AHPS) is obtained from the dried roots of Astragalus membranaceus (Fisch.) Bunge var. mongholious (Bunge) Hsiao. In the present study, we observed its effects on erythrocyte immune adherence function in mice with adjuvant-induced arthritis (AA). The mice were treated intragastrically with AHPS of 1 000, 500, and 250 mg x kg(-1) x d(-1) separately and treated with tripterygium glycosides (TG) of 60 mg x kg(-1) x d(-1) as positive control. The number of complement receptor type 1 (CR1) on erythrocyte, the concentration of circulating immune complex (CIC) in serum and the amount of immune complex (IC) deposition in synovium of knee joint were determined by flow cytometry, polyethylene glycol (PEG-6000) precipitation and ponceau S (P-S) staining and fluorescent immunohistochemistry respectively. The pathological change of knee joint was evaluated by histological section. The results showed that both AHPS and TG improved significantly the primary and secondary local or systemic symptoms of the mice with AA and reduced the synovium hyperplasia, inflammatory cell infiltrate, pannus and cartilage demolish of knee joint, and AHPS of 1 000, 500, and 250 mg x kg(-1) x d(-1) could significantly increase the number of CR1 on erythrocyte, improve the elimination of CIC in the peripheral blood and reduce the deposition of IC in joint synovium in a dose-dependent manner (P < 0.01 or P < 0.05). The results indicate that one of the therapeutic effective mechanisms of AHPS on mice with AA could be to increase gene expression of CR1 of mice with AA.
Animals ; Antigen-Antibody Complex ; blood ; metabolism ; Arthritis, Experimental ; metabolism ; pathology ; Astragalus Plant ; chemistry ; Dose-Response Relationship, Drug ; Erythrocytes ; immunology ; Knee Joint ; pathology ; Male ; Mice ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Polysaccharides ; administration & dosage ; isolation & purification ; pharmacology ; Random Allocation ; Receptors, Complement ; blood ; Synovial Membrane ; immunology

This study is to investigate the effects of paeoniflorin (Pae) on the levels of related serum antibodies and cAMP of splenocytes in rats with adjuvant arthritis. Complete Freund's adjuvant was used to induce AA in rats. The level of circulating immune complexes in serum was determined by PEG6000 assay, and the levels of anti-C II antibody and anti-TB antibody in serum were measured by enzyme-linked immunosorbent assay (ELISA), the level of cAMP in splenocytes was measured by radioimmunoassay, separately. Pae (25, 50, and 100 mg x kg(-1)) and GTW (40 mg x kg(-1)) were given by intragastric administration for 7 days from the 17th day after immunization. Pae (50 and 100 mg x kg(-1)) reduced the levels of circulating immune complexes, anti-C II antibody and anti-TB antibody in serum in rats with adjuvant arthritis. The inhibition ratios of Pae groups to AA model group were dosage-dependent; Pae (12.5, 62.5, and 312.5 mg x L(-1)) decreased the elevated levels of cAMP in splenocytes in vitro. Pae (ig) decreased the levels of related serum antibodies and elevated the level of cAMP in rats with adjuvant arthritis.
Animals ; Antibodies, Bacterial ; blood ; Antigen-Antibody Complex ; blood ; Arthritis, Experimental ; chemically induced ; immunology ; Benzoates ; isolation & purification ; pharmacology ; Bridged-Ring Compounds ; isolation & purification ; pharmacology ; Cyclic AMP ; metabolism ; Dose-Response Relationship, Drug ; Freund's Adjuvant ; Glucosides ; isolation & purification ; pharmacology ; Isoantibodies ; blood ; Monoterpenes ; Mycobacterium tuberculosis ; immunology ; Paeonia ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spleen ; cytology ; metabolism

OBJECTIVETo identify autoepitopes of E2 subunit of pyruvate dehydrogenase complex (PDC-E2) specific CD8+ CTL in primary biliary cirrhosis (PBC) patients.

METHODSAn online database SYFPEITHI was applied to predict HLA-A*0201 restricted epitopes which located in PDC-E2 30-50 aa and 150-190 aa where B-cell epitopes clustered with CD4+ T-cell epitopes. T2 cell line reconstitution and stabilization assay, induction of specific CTL lines from peripheral blood mononuclear cells (PBMCs) of patients with PBC and cytotoxicity of peptides-induced CTL were performed to screen the epitopes from those candidates.

RESULTSFive potential epitopes were predicted by database. Of the 5 candidates, two peptides 159-167 aa and 165-174 aa, with highly binding activity to HLA-A*0201 molecules, could stimulate PBMCs from most HLA-A*0201 positive PBC patients to proliferate and peptide-induced CTL lines showed specific cytotoxicity.

CONCLUSIONPeptides of KLSEGDLLA (159-167 aa) and LLAEIETDKA (165-174 aa) in the inner lipoyl domain of PDC-E2 are HLA-A*0201 restricted CD8+ CTL immunodominant epitopes in PBC.

Antibody-Producing Cells ; cytology ; Autoantigens ; immunology ; Autoimmunity ; CD8-Positive T-Lymphocytes ; cytology ; immunology ; metabolism ; Cell Line ; Dihydrolipoyllysine-Residue Acetyltransferase ; Epitope Mapping ; Epitopes, T-Lymphocyte ; immunology ; HLA-A Antigens ; immunology ; HLA-A2 Antigen ; Humans ; Liver Cirrhosis, Biliary ; enzymology ; genetics ; immunology ; Phenotype ; Protein Binding ; Pyruvate Dehydrogenase Complex ; genetics ; immunology ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology

DNA double-strand break (DSB) is the most severe form of DNA damage, which is repaired mainly through high-fidelity homologous recombination (HR) or error-prone non-homologous end joining (NHEJ). Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer. Nicotinamide phosphoribosyltransferase (Nampt), which is involved in nicotinamide adenine dinucleotide metabolism, is overexpressed in a variety of tumors. In this report, we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80, which are key factors in HR and NHEJ, respectively. Depletion of Nampt by small interfering RNA (siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair. Furthermore, the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining, indicating a delay in the onset of cellular senescence in normal human fibroblasts. Taken together, our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair, contributing to the acceleration of cellular senescence.
Antigen-Antibody Complex ; metabolism ; Antigens, Nuclear ; genetics ; metabolism ; Carrier Proteins ; genetics ; metabolism ; Cell Line ; Cell Proliferation ; Cellular Senescence ; DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; DNA Repair ; DNA-Activated Protein Kinase ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Fibroblasts ; cytology ; HeLa Cells ; Homologous Recombination ; genetics ; physiology ; Humans ; Ku Autoantigen ; Nicotinamide Phosphoribosyltransferase ; genetics ; metabolism ; physiology ; Nuclear Proteins ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; beta-Galactosidase ; metabolism