Systemic lupus erythematous (SLE) is a systemic autoimmune disease with multi-organ inflammation caused by the production of pathogenic autoantibodies and immune complexes reflecting a global loss of tolerance. Lupus nephritis (LN) is present in approximately 60% of SLE patients and is considered a major predictor of a poor prognosis. To date, many studies utilizing genomics, transcriptomics, epigenetics, metabolomics, and microbiome have been conducted on a range of animal models and lupus patients to understand the pathogenesis of SLE and LN. Collectively, these studies support the concept that LN is caused by increased cell death, which has not been properly dealt with; abnormal innate immunity; hyperactive adaptive immunity; and genetic variants triggered by a range of environmental factors. This review summarizes the results from studies that contributed strongly to elucidating the pathogenesis of SLE and LN, highlighting the immunological and non-immunological mechanisms.
Adaptive Immunity ; Allergy and Immunology ; Antigen-Antibody Complex ; Apoptosis ; Autoantibodies ; Autoimmune Diseases ; Cell Death ; Epigenomics ; Genomics ; Humans ; Immunity, Innate ; Inflammation ; Lupus Nephritis* ; Lymphocytes ; Metabolomics ; Microbiota ; Models, Animal ; Prognosis ; Wolves*

This study is to explore the interventional effects of fluvastatin on anti-beta2GPI/beta2GPI-induced activation in THP-1 mononuclear cells. In vitro, human mononuclear cells THP-1 were treated with fluvastatin, LPS and anti-beta2GPI/beta2GPI, then the TF expression on THP-1 cells was detected by real-time quantitative PCR (RT-qPCR) or TF activity was detected by kit. TNF-alpha mRNA and its protein expression were investigated by RT-PCR and ELISA kit. The expression of phospho-NF-kappaB p65 and inhibitory protein of NF-kappaB (IkappaB-alpha) were measured by Western blotting. The results suggested that the expression of TF and TNF-alpha on THP-1 cells was significantly up-regulated with treatment of anti-beta2GPI/beta2GPI complex (100 mg x L(-1)), compared with that of untreated cells (P < 0.05). Fluvastatin (50 mg x L(-1)) could decrease TF (mRNA and activity) expression and the level of TNF-alpha (mRNA and protein) in THP-1 cells with anti-beta2GPI/beta2GPI complex. The expression of TF and TNF-alpha was shown in a concentration-dependent manner. Moreover, anti-beta2GPI/beta2GPI complex could downregulate IkappaB-alpha levels and increase the levels of phospho-NF-kappaB p65. And these effects of anti-beta2GPI/beta2GPI complex could be blocked by fluvastatin. In conclusion, fluvastatin may interfere the expression and regulation of NF-kappaB signal transduction pathway, thereby inhibit the effects of anti-beta2GPI/beta2GPI on activation of THP-1 cells, by decreasing the expression of TF and TNF-alpha.
Antigen-Antibody Complex ; pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Fatty Acids, Monounsaturated ; administration & dosage ; pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; pharmacology ; I-kappa B Proteins ; metabolism ; Indoles ; administration & dosage ; pharmacology ; Monocytes ; cytology ; metabolism ; NF-KappaB Inhibitor alpha ; Phosphorylation ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; Thromboplastin ; genetics ; metabolism ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; beta 2-Glycoprotein I ; antagonists & inhibitors ; immunology

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

OBJECTIVETo investigate the significance of increasing circulating immune complex (CIC) in patients during the progression from chronic hepatitis B to hepatocellular carcinoma (HCC).

METHODSSerum levels of CIC from 20 hospitalized patients diagnosed by pathology with primary HCC, and 13 with hepatic hemangioma, and from 45 subjects with chronic HBV infection who finally developed into HCC (45 cases), and age- and gender-matched 45 subjects who kept the chronic HBV infection after consecutively followed up for 10 - 13 years by June of 2009 were quantified by ELISA. The serum levels of anti liver-kidney microsomal (anti LKM-1) antibodies were also measured by ELISA, and that of HBV-DNA were quantified by Taqman probe-based real time PCR in the followed up chronic HBV infection subjects. In the 45 chronic HBV subjects who finally developed into HCC and the 45 controls, serum samples were collected and determined at 3 time points: the baseline when the subjects were recruited, the middle point during the follow-up, and the end of follow-up.

RESULTSThe serum level of CIC was significantly higher in the 20 HCC patients than that in the 13 hemangioma cases (P < 0.001). When HCC was diagnosed, the CIC concentration was significantly higher than that in the baselines (P < 0.001) in the 45 chronic HBV subjects who finally developed into HCC after the consecutively follow-up for 5 - 13 years. Of them, 36 patients (80.0%) showed progressively increased CIC during the follow-up (P < 0.001). In the controls, the CIC levels were kept relatively stable during the follow-up. Among them, 17 patients (37.8%) showed CIC slightly increased (P = 0.046). Kaplan-Meier survival analysis indicated that elevated serum CIC during the follow-up increased cumulative HCC incidence (HR = 2.77, 95%CI 1.47 - 5.22). In addition, the serum levels of anti-LKM-1 and HBV-DNA were also significantly higher in the patients who finally progressed into HCC than that in the controls and maintained at a high level during the follow-up tested at all the 3 time points. Further analysis indicated that the serum level of CIC was correlated with that of serum HBV-DNA only when HCC was diagnosed (r = 0.344, P = 0.026).

CONCLUSIONProgressive increase of serum CIC level may be one of risk factors reflecting HCC development from chronic HBV infection.

Antigen-Antibody Complex ; blood ; Autoantibodies ; blood ; Carcinoma, Hepatocellular ; immunology ; virology ; DNA, Viral ; blood ; Disease Progression ; Female ; Follow-Up Studies ; Hemangioma ; immunology ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; complications ; immunology ; Humans ; Liver Neoplasms ; immunology ; virology ; Male ; Middle Aged ; Risk Factors

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

Animals ; Antigen-Antibody Complex ; therapeutic use ; DNA, Viral ; blood ; Dendritic Cells ; immunology ; Ducks ; Female ; Hepatitis B Antibodies ; blood ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; immunology ; therapeutic use ; Hepatitis B e Antigens ; blood ; immunology ; Hepatitis B virus ; immunology ; Hepatitis B, Chronic ; blood ; immunology ; therapy ; Humans ; Male ; Mice ; T-Lymphocytes

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated complication of heparin treatment that can lead to thrombosis and thromboembolism. HIT is mainly caused by immunoglobulin G (IgG) class among anti-heparin/platelet factor 4 antibodies that bind to epitopes on platelet factor 4 (PF4) released from activated platelets that developed when it forms complexes with heparin. Platelet aggregation and hypercoagulation status result from this process. Besides, the reactions between antibodies and vascular endothelial cells and monocytes are involved in HIT. Laboratory detection of anti-heparin/platelet factor 4 antibodies after heparin administration may help diagnose HIT early. Tests for detecting antibodies to the heparin/PF4 complex can be classified into functional platelet assays (which rely on the demonstration of platelet activation) and immunoassays (which detect the presence of an antibody without regard for its functional ability). But there is no simple and effective test available currently. In this article the anti-heparin/platelet factor 4 antibodies, pathogenesis of HIT, clinical laboratory assays and immunoassays are reviewed.
Antigen-Antibody Complex ; immunology ; Heparin ; adverse effects ; immunology ; Humans ; Immunoglobulin G ; immunology ; Platelet Aggregation ; Platelet Factor 4 ; immunology ; Thrombocytopenia ; chemically induced ; immunology

OBJECTIVETo study the correlation of erythrocyte immune function between normal neonates and their mothers and the influence of various obstetric factors on neonatal erythrocyte immune function.

METHODSThe adherent rate of complement 3b-receptor on the surface of red blood cells (RBC-C3bRR) and the immune complex adherent rate of red blood cells (RBC-ICR) were detected using the erythrocyte saccharomyces rosette test in 104 normal neonates and their mothers. The correlation of erythrocyte immune function between neonates and their mothers was evaluated by the maternal-infant paired test.

RESULTSThe levels of RBC-C3bRR (16.80 +/- 1.56% vs 16.23 +/- 1.63%; P < 0.05) and RBC-ICR (5.72 +/- 1.63% vs 5.02 +/- 1.38%; P < 0.01) in neonates were significantly higher than those in their mothers. There was a significantly positive correlation in RBC-ICR levels between neonates and their mothers (r = 0.28, P < 0.05). No correlation was found in RBC-C3bRR levels between the two groups. Neither RBC-C3bRR nor RBC-ICR levels of neonates were associated with various obstetric factors such as amniotic fluid, placenta, umbilical cord, parturient patterns, and puerperal anemia and pregnancy-induced hypertension syndrome.

CONCLUSIONSThe erythrocyte immune function in neonates has a relatively mature level and correlates with their mothers' erythrocyte immune function. Various obstetric factors have no influences on neonatal erythrocyte immune function.

Antigen-Antibody Complex ; immunology ; Erythrocytes ; immunology ; Female ; Fetal Blood ; immunology ; Humans ; Infant, Newborn ; immunology ; Linear Models ; Male ; Pregnancy ; Receptors, Complement 3b ; analysis ; Rosette Formation

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

OBJECTIVEThis study investigated the clinical manifestations and renal pathological findings of 95 children with Henoch-Schonlein purpura nephritis (HSPN) in order to explore the relationship between clinical manifestations and renal pathology in HSPN.

METHODSAccording to clinical manifestations, 95 HSP patients were classified into six clinical groups: 1) normal urine analysis; 2) isolated hematuria or proteinuria; 3) proteinuria with hematuria; 4) acute nephritis; 5) nephrotic syndrome; 6) acute nephritis with over 50 mg/(kg.d) of proteinuria. The severity of the renal pathological findings was determined based on the classification of the International Study of Kidney Disease (ISKDC), including grades I-VI. The relationship between clinical manifestations and the severity of renal pathological findings was studied.

RESULTSNephrotic syndrome was the most common clinical diagnosis (26 cases), followed by proteinuria with hematuria (23 cases), normal urine analysis (20 cases), isolated hematuria or proteinuria (15 cases), acute nephritis with over 50 mg/(kg.d) of proteinuria (7 cases) and acute nephritis (4 cases). Twenty-five out of 26 patients with nephrotic syndrome had an ISKDC classification of grade III-IV. All of the four patients with acute nephrits had a classification of grade IIIb. The 7 cases of acute nephritis with over 50 mg/(kg.d) of proteinuria had a classification of grade IIIa-V. The 20 patients with normal urine analysis had a classification of grade Iia- IIIb. There were no significant differences in ISKDC classification among the patients with normal urine analysis, isolated hematuria or proteinuria, and hematuria plus proteinuria. As the course progressed, the degree of renal pathological changes in patients with isolated hematuria or proteinuria and hematuria plus proteinuria became more serious. Of all the 95 patients, 58% had co-deposition of immunoglobulins A, G and M. The percentage of co-deposition of immunoglobulins A, G and M was related to the disease course and the severity of renal pathological findings.

CONCLUSIONSHSPN children with nephrotic syndrome or acute nephritis with or without proteinuria had relatively severe renal pathological changes. The clinical manifestations were not always in parallel with the severity of renal pathological findings in HSPN children. With the course progressing, the renal pathological changes tended to be serious. The severe renal pathological manifestations came with co-deposition of immunogolobulins A, G and M in the glomerulin.

Adolescent ; Antigen-Antibody Complex ; analysis ; Child ; Child, Preschool ; Female ; Humans ; Kidney ; pathology ; Male ; Nephritis ; complications ; immunology ; pathology ; Purpura, Schoenlein-Henoch ; complications ; immunology ; pathology