Home  About us  Contact
 

Immune Complexes (immune + complex)

Distribution by Scientific Domains
Medical Sciences86%
Life Sciences11%
Distribution within Medical Sciences
Immunology37%
Hematology10%

Terms modified by Immune Complexes

  • immune complex deposition
    		•
  • immune complex glomerulonephritis
    		•

    Selected Abstracts

    Selective Removal of Circulating Immune Complexes from Patient Plasma

    ARTIFICIAL ORGANS, Issue 2 2002
    Siegfried Kunkel
    Abstract: The principle of a patient-specific immunoadsorber (PsIA) is demonstrated. Studies with model systems (HSA/anti-HSA) on immobilization, stability, and leakage form the basis for the presented fast-performance liquid chromatography (FPLC) and batch experiments, which were conducted using two different protein A adsorbers and autologous and heterologous PsIA systems. Experiments to determine the binding capacity of protein A adsorbers and PsIAs are described. In all experiments, the adsorption of plasma IgG, total protein, and C1q and C3d circulating immune complexes were measured. Plasma of patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) was investigated. Analysis was performed in both the initial plasma and the flow-through or supernatant. Results of the investigations using FPLC and batch experiments were compared. Autologous PsIA systems are suitable for the selective removal of elevated levels of circulating immune complexes in the plasma. [source]

    Fc,RII expression on follicular dendritic cells and immunoreceptor tyrosine-based inhibition motif signaling in B,cells

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2004
    Yüksel Aydar
    Abstract Immune complexes (IC) initiate immunoreceptor tyrosine-based inhibition motif (ITIM) signaling and inhibit B,cell activation by coligating B,cell receptor for antigen (BCR) and Fc,RII. Nevertheless, IC on follicular dendritic cells (FDC) stimulate rapid germinal center (GC) B,cell proliferation suggesting that interactions between IC and FDC render IC capable of B,cell activation. Tounderstand this, we studied the kinetics of FDC Fc,RII and complement receptors,1 and,2 (CR1&2) expressions during the GC reaction and determined whether FDC Fc,RII could bind Fc in IC and block ITIM signaling. Mice were immunized with sheep red blood cells (SRBC), and CR1&2 and Fc,RII levels in FDC reticula were monitored. The role of FDC Fc,RII was studied using anti-BCR-stimulated A20 cells. Levels of FDC Fc,RII in spleens of SRBC-injected mice increased within 24,h and were dramatically increased (,50-fold) on days,3 and,5. In contrast, CR1&2 levels increased less than twofold. Addition of normal FDC, but not FDC lacking Fc,RII, reduced and reversed anti-BCR-induced SH2 domain-containing inositol phosphatase (SHIP)-1 phosphorylation in A20 cells. FDC wereable to induce normal recall responses even after overnight incubation of the lymphocytes with IC to stimulate ITIM signaling. Engagement of Ig Fc with numerous Fc,RII on FDC appears to minimize IC-induced ITIM signaling. Thus, rapid up-regulation of FDC Fc,RII may explain why poorly immunogenic IC are rendered highly immunogenic when presented by FDC in GC. [source]

    Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system

    CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2004
    A. TEJDE
    SUMMARY Immune complexes (IC) can induce cytokine production in vitro. While immune aggregates (IA) consisting of heat-aggregated gamma globulin (HAGG) as model IC increased interleukin (IL)-10 levels in cell cultures with native human serum, IL-12p40/p70 production was inhibited. Three series of experiments suggested that the effects of IA on IL-12 production depended on a functionally intact complement system: (1) heat-inactivation of serum inverted the inhibitory effect of IA on IL-12p40/p70 production; (2) IA-induced IL-12p40 production in a C4 deficient serum was lowered by addition of C4; and (3) addition of the peptide compstatin, which blocks C3 activation, mimicked the effects of heat inactivation on IL-12p40 levels. Neutralization of IL-12 resulted in modestly increased IL-10 levels, while neutralization of IL-10 had no effects on IL-12p40 production. IA-induced production of IL-10 was partially blocked by anti-Fc,,RII antibodies, whereas Fc,,R or CR blockade had no effect on IL-12p40 production. IC and local or systemic complement activation characterize rheumatoid arthritis, systemic lupus erythematosus and many malignancies. Different and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in these diseases, where control of the complement system might be a way to direct IC-induced cytokine production in either a type 1 or type 2 direction. [source]

    Heteropolymer-mediated clearance of immune complexes via erythrocyte CR1: mechanisms and applications

    IMMUNOLOGICAL REVIEWS, Issue 1 2001
    Margaret A. Lindorfer
    Summary: Opsonization of particulate pathogens by antibodies and complement can lead to their binding to the complement receptor (CR1), specific for C3b, on primate erythrocytes (E). This process of immune adherence may play a role in immunologic defense by immobilizing bacteria and viruses, thus preventing them from leaving the bloodstream to invade susceptible tissue and organs. Immune adherence of C3b-opsonized and immune complexed pathogens to E may also facilitate their transfer to, and destruction by, fixed tissue macrophages. We have used mAbs specific for CR1 crosslinked with pathogen specific mAbs to generate heteropolymers (HP) which can bind a wide range of substrates to primate erythrocytes. Both prototype and bonafide pathogens bound to primate E via HP are handled in the circulation of non-human primates in a manner which appears to be virtually identical to the mechanism by which C3b-opsonized substrates bound to E CR1 are cleared. In this process of focused phagocytosis, Fc receptors on the phagocytic cell engage the E-bound complex, CR1 is removed by proteolysis, and the entire immune complex and CR1 are internalized while sparing the E. It may be possible to use HP to target pathogens in the bloodstream in a wide range of therapeutic applications. [source]

    Lack of effect of a single injection of human C-reactive protein on murine lupus or nephrotoxic nephritis

    ARTHRITIS & RHEUMATISM, Issue 1 2010
    Francesco Carlucci
    Objective It has been reported that a single dose of human C-reactive protein (CRP) can prevent and reverse the renal damage in murine models of spontaneous lupus, as well as the rapid-onset immune complex disease induced in the accelerated nephrotoxic nephritis (ANTN) model. This study was undertaken to attempt to replicate these observations using a highly purified and fully characterized human CRP preparation. Methods (NZB × NZW)F1 (NZB/NZW) mice were treated with a single 200-,g subcutaneous injection of CRP or control reagents either before disease onset at 4 months of age or when high-grade proteinuria was present at 7 months of age. Mice were monitored at least monthly for proteinuria and autoantibody levels. ANTN was induced by preimmunizing C57BL/6 mice with sheep IgG, followed 5 days later by injection of sheep anti-mouse glomerular basement membrane antibody and CRP or control reagents. Renal disease was assessed by regular urinalysis and histologic evaluation. Results CRP treatment of NZB/NZW mice, either early or late in the disease, had no effect on proteinuria, autoantibody titers, or survival. CRP administration did not reduce renal injury or alter disease in the ANTN model. Human serum amyloid P component, a pentraxin protein that is very closely related to CRP, similarly had no effect. Conclusion Our completely negative observations do not confirm that human CRP has reproducible antiinflammatory or immunomodulatory effects in these murine models, nor do they support the suggestion that CRP might be useful for therapy of lupus or immune complex,mediated nephritis. [source]

    C1q inhibits immune complex,induced interferon-, production in plasmacytoid dendritic cells: A novel link between C1q deficiency and systemic lupus erythematosus pathogenesis

    ARTHRITIS & RHEUMATISM, Issue 10 2009
    Christian Lood
    Objective C1q deficiency is the strongest risk factor known for the development of systemic lupus erythematosus (SLE), since almost all humans with a genetic deficiency of C1q develop this disease. Low C1q serum concentration is also a typical finding in SLE during flares, emphasizing the involvement of C1q in SLE pathogenesis. Recent studies have revealed that C1q has a regulatory effect on Toll-like receptor,induced cytokine production. Therefore, we undertook this study to investigate whether C1q could regulate production of interferon-, (IFN,). Methods Peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) were stimulated with 3 known interferogenic stimuli and cultured with physiologic concentrations of C1q. IFN, production was determined by an immunoassay. Results C1q significantly inhibited PBMC IFN, production induced by RNA-containing immune complexes (ICs), herpes simplex virus (HSV), and CpG DNA. C1q also inhibited PDC IFN, production induced by ICs and CpG DNA but increased PDC IFN, production induced by HSV. The regulatory role of C1q was not specific for IFN, but was also seen for interleukin-6 (IL-6), IL-8, and tumor necrosis factor ,. We demonstrated binding of C1q to PDCs both by surface plasmon resonance interaction analysis and by flow cytometry, and we also demonstrated intracellular detection of 2 C1q binding proteins. Conclusion Our findings contribute to the understanding of why C1q deficiency is such a strong risk factor for SLE and suggest an explanation for the up-regulation of the type I IFN system seen in SLE patients. [source]

    Different amplifying mechanisms of interleukin-17 and interferon-, in Fc, receptor,mediated cartilage destruction in murine immune complex,mediated arthritis

    ARTHRITIS & RHEUMATISM, Issue 2 2009
    Lilyanne C. Grevers
    Objective Previously, we reported that interferon-, (IFN,) aggravates cartilage destruction in immune complex (IC),mediated arthritis via up-regulation of activating Fc, receptors (Fc,R). Recently, we found that interleukin-17 (IL-17) also aggravates cartilage destruction in arthritis models in which ICs are involved, but the underlying mechanism remains unknown. This study was undertaken to determine the role of IL-17 in Fc,R-mediated cartilage destruction in IC-mediated arthritis and to compare its effect with that of IFN,. Methods IC-mediated arthritis was passively induced in ,-chain,/, mice, which lack functional activating Fc,R, and in wild-type controls. AdIL-17 or a control vector was injected into the knee joints 1 day prior to induction of IC-mediated arthritis. Knee joints were isolated for histologic analysis, and synovium samples were obtained for reverse transcriptase,polymerase chain reaction (RT-PCR). Macrophage (RAW 264.7) cell lines and polymorphonuclear cell (PMN; 32Dcl3) lines were stimulated with IFN, or IL-17 for analysis of Fc,R expression using RT-PCR and fluorescence-activated cell sorting. Results IL-17 overexpression prior to induction of IC-mediated arthritis significantly aggravated cartilage destruction and inflammation, characterized by a massive influx of PMNs, which adhered to the cartilage surface. Although IL-17 overexpression increased Fc,R messenger RNA levels in the synovium, in vitro stimulation of macrophages and PMNs revealed that, in contrast to IFN,, IL-17 did not directly regulate Fc,R expression. Despite similar inflammation in AdIL-17,enhanced IC-mediated arthritis in ,-chain,/, mice and wild-type controls, severe cartilage destruction and PMN adherence were completely absent in ,-chain,/, mice. Conclusion Our findings indicate that IL-17,mediated aggravation of cartilage destruction in IC-mediated arthritis is Fc,R dependent. However, in contrast to IFN,, which directly up-regulates Fc,R expression on macrophages and PMNs, IL-17 enhances cartilage destruction by increasing the local amount of Fc,R-bearing neutrophils. [source]

    Increased expression of Fc, receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor , and matrix metalloproteinase

    ARTHRITIS & RHEUMATISM, Issue 4 2003
    Arjen B. Blom
    Objective To evaluate Fc, receptor (Fc,R) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor , (TNF,), interleukin-1, (IL-1,), IL-12, and matrix metalloproteinase 1 (MMP-1). We also sought to determine whether mature macrophages from RA patients express aberrant levels of Fc,RI, Fc,RII, and Fc,RIII, and to determine the production of inflammatory mediators after immune complex (IC) stimulation. Methods Immunohistochemistry was performed on cryostat sections of synovial biopsy specimens obtained from 27 RA patients and 5 controls. Fc,R I, II, and III were detected, as well as the proinflammatory mediators IL-1, TNF,, IL-12, and MMP-1. Monocytes were isolated from the blood of 10 RA patients and 10 healthy controls and cultured for 7 days with macrophage colony-stimulating factor to obtain macrophages. Using fluorescence-activated cell sorting, the expression of Fc,RI, Fc,RII, and Fc,RIII was determined. On day 7, macrophages were stimulated with heat-aggregated gamma globulins (HAGGs) for 24 hours. Production of cytokines was measured using enzyme-linked immunosorbent assay, and production of gelatinases/collagenases was measured by degradation of fluorescent gelatin. Results Immunohistochemistry showed higher Fc,RII and Fc,RIII expression in RA synovium than in controls. Fc,RII and Fc,RIII, but not Fc,RI, were highly correlated with the number of synovial macrophages. Consistent with this, TNF, expression correlated positively with Fc,RIII expression. Moreover, MMP-1 expression strongly correlated with Fc,R I, II, and III expression. Mature macrophages from RA patients showed significantly enhanced expression of Fc,RII and Fc,RIII compared with controls. Twenty-four hours after stimulation of RA macrophages with HAGGs, significantly higher production of TNF, and gelatinase/collagenase was measured. Conclusion RA synovium and mature RA macrophages express significantly elevated levels of Fc,RII and Fc,RIII, resulting in much higher production of TNF, and gelatinase/collagenase after IC stimulation. These data suggest that disturbed expression of Fc,R on mature synovial macrophages is involved in the pathology of RA. [source]

    Analysis of immune complexes by capillary electrophoresis

    ELECTROPHORESIS, Issue 12 2008
    Zak K. Shihabi Dr.Article first published online: 21 MAY 200
    Abstract A simple method for immune complexes (IC) analysis by CE is described. This method combines the ease of precipitation of the IC by polyethylene glycol with the separation power of CE. The advantage of this method is a better quantitation of the IC, since it corrects and eliminates the interferences from other serum proteins. It also reveals the composition (monoclonality) of the precipitate. Three types of IC have been detected in this method: monoclonal, polyclonal and mixed (mono-polyclonal) IC. Furthermore, the method is rapid and simple. [source]

    IgG2 containing IgM,IgG immune complexes predominate in normal human plasma, but not in plasma of patients with warm autoimmune haemolytic anaemia

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2006
    Dorothea Stahl
    Abstract:, The different physicochemical and sterical properties of IgG subclasses may favour a selective enrichment of defined IgG subclasses in IgM,IgG immune complexes (IC) of human plasma under physiological conditions. Such enrichment of IgG subclasses in IgM,IgG IC of plasma may differ from the normal IgG subclass distribution in plasma itself, and contribute to the physiological functions of IgM,IgG IC. Systematic studies on the IgG subclass distribution in IgM,IgG IC in humans are lacking. Using specific analytical techniques to characterise IgM,IgG IC in human plasma (i.e. fast protein liquid chromatography, enzyme-linked immunosorbent assay, affinity biosensor technology), and taking warm autoimmune haemolytic anaemia (WAIHA) of humans as a disease model, we here demonstrate that: (i) IgG2 is the predominant IgG subclass in IgM,IgG IC under physiological conditions, (ii) the predominance of IgG2 within IgM,IgG IC may get lost in polyclonal IgG-mediated autoimmune disease and (iii) the IgG subclass distribution in IgM,IgG IC influences the interaction between IC and blood cells involved in antigen presentation. The data presented here therefore extend the physiological function of IgG2, which is the protective immune response towards carbohydrate antigens in bacterial infections, and suggest IgG2-dependent regulation of immune responses to self-immunoglobulin in humans. The disturbed IgG subclass distribution in IgM,IgG IC of patients with WAIHA might influence activity of self-reactive B cells involved in the pathophysiology of the disease. [source]

    Plasmacytoid dendritic cell activation by foot-and-mouth disease virus requires immune complexes

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006
    Laurence Guzylack-Piriou
    Abstract Natural IFN-producing cells (NIPC), also called plasmacytoid dendritic cells, represent an essential component of the innate immune defense against infection. Despite this, not much is known about the pathways involved in their activation by non-enveloped viruses. The present study demonstrates that the non-enveloped foot-and-mouth disease virus (FMDV) cannot stimulate IFN-, responses in NIPC, unless complexed with FMDV-specific immunoglobulins. Stimulation of NIPC with such immune complexes employs Fc,RII ligation, leading to strong secretion of IFN-,. In contrast to the stimulation of NIPC by many enveloped viruses, FMDV induction of IFN-, production requires live virus. It is necessary for the virus to initiate its replicative cycle. Moreover, it is an abortive replication, as witnessed by the decrease of dsRNA levels and viral titers with time post infection. Sensitivity of the NIPC stimulation to wortmannin and chloroquin, but not leupeptin, indicates an essential role for the pre-lysosomal stage endosomal compartment. In conclusion, the present study demonstrates that immune complexes provide the means for a non-interferogenic virus to induce IFN-, responses by NIPC. This indicates an important link between NIPC and antibodies in immune responses against non-enveloped viruses such as FMDV. [source]

    A crucial role for macrophages in the pathology of K/B,×,N serum-induced arthritis

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2005
    Samuel Solomon
    Abstract Autoantibodies in the form of immune complexes are known to be crucial mediators in initiating inflammation in a variety of autoimmune diseases. This has been well documented in the anti-collagen,II antibody-induced arthritis animal model for a long time now. Recently, in the K/B,×,N mouse model (the F1 of the TCR-transgenic KRN and the diabetic NOD mice), anti-glucose-6-phosphate isomerase (GPI) autoantibodies have been shown to induce arthritis. Experimental work in the K/B,×,N model demonstrated key roles of autoantigenic immune complexes activating the alternative pathway of complement, the subsequent association with C5aR and Fc,RIII-mediated cell activation and production of the inflammatory cytokines IL-1 and TNF-,, finally leading to joint destruction. The presence of high amounts of inflammatory cytokines and matrix-degrading proteases at sites of inflammation obviously put the cytokine-producing macrophages as the next target for investigation in this model. Here, we show that mice depleted of macrophages by clodronate liposome treatment are completely resistant to K/B,×,N serum-induced arthritis. Reconstituting clodronate liposome-treated mice with macrophages from naive animals could reverse this resistance. Also, we found that deficiencies in the Wiskott-Aldrich syndrome protein and CD40, which are both implicated in macrophage activation, chemotaxis and phagocytosis, are not essential in serum-induced arthritis. Mast cell degranulation was seen in arthritogenic serum-treated mice even in the absence of macrophages, possibly suggesting that mast cell degranulation/activation acts hierarchically before macrophages in the inflammatory cascade of anti-GPI antibody-induced arthritis. [source]

    Deposition of chromatin-IgG complexes in skin of nephritic MRL-lpr/lpr mice is associated with increased local matrix metalloprotease activities

    EXPERIMENTAL DERMATOLOGY, Issue 8 2010
    Annica Hedberg
    Please cite this paper as: Deposition of chromatin-IgG complexes in skin of nephritic MRL-lpr/lpr mice is associated with increased local matrix metalloprotease activities. Experimental Dermatology 2010; 19: e265,e274. Abstract:, Chromatin-IgG complexes appear as electron dense structures (EDS) in glomerular basement membranes in lupus nephritis. Here, we present results of comparative analyses of the composition of EDS in murine lupus dermatitis and nephritis. One focus was to perform an analytical approach to understand why such complex structures bind skin basement membrane components. Transcription of skin membrane-encoding genes was analysed to see if expression of such genes was increased, eventually indicating that binding capacity of immune complexes increased when dermatitis developed. Variations in matrix metalloprotease 2 (MMP2), MMP9 and Dnase1 mRNA levels and enzymatic activities were correlated with circulatory chromatin-IgG complexes and deposition in skin. We also examined if glomerular deposits of EDS predicted similar deposits in skin of (NZB × NZW)F1 or MRL-lpr/lpr mice, as we observed chromatin-IgG complexes in capillary lumina in skin and glomeruli in both strains. EDS consisting of chromatin fragments and IgG were found sub-epidermally in skin with LE-like lesions of end-stage nephritic MRL-lpr/lpr mice. Dermal MMP-encoding genes were up-regulated during disease progression, and gelatinolytic activity was increased in affected skin. Dnase1 mRNA level and total nuclease activity remained stable in skin during the disease, in contrast to progressive loss of renal Dnase1 mRNA and total renal nuclease activity during development of nephritis. Loss of renal Dnase1 may explain release of chromatin fragments, while increased MMP activity may disrupt membranes making them accessible for chromatin fragment-IgG complexes. Circulatory chromatin-IgG complexes, and up-regulated intradermal MMP activity may be crucial for deposition of immune complexes in skin of lupus-prone mice. [source]

    Different pathways leading to cutaneous leukocytoclastic vasculitis in mice

    EXPERIMENTAL DERMATOLOGY, Issue 6 2001
    C. Sunderkötter
    Abstract: To investigate the pathomechanisms of leukocytoclastic vasculitis (LcV) we compared mouse models of LcV with non-vasculitic irritant contact dermatitis (ICD). Criteria for LcV as met by the immune complex-mediated Arthus reaction (Art-r) were also fulfilled by the localized Shwartzman reaction (Shw-r) and by cutaneous Loxoscelism (Lox) (injection of venom from Loxosceles reclusa containing sphingomyelinase D). After depletion of PMN (by ,-irradiation) vessel damage could not be elicited in these models, distinguishing them from models of direct endothelial insult (necrotizing ICD). Depletion of complement could only delay, but not inhibit the Art-r, and did not change ICD, Lox or the Shw-r. The Shw-r exclusively revealed a sustained local expression of vascular adhesion molecules for 24 h in the preparatory phase (LPS s.c.), not observed in the Art-r, in Lox or ICD. Subsequent challenge with LPS i.p. was associated with upregulation of Mac-1 and ICAM-1 on PMN, but not of VLA-4 or LFA-1 (FACS analysis). Cytokines which were able to replace LPS in priming for LcV in the Shw-r (TNF-, and IL-1,) also induced sustained expression of adhesion molecules, whereas IL-12 and IFN-, did neither. Neutralizing IL-12 or IFN-, also inhibited neither LcV nor sustained expression of adhesion molecules, whereas anti-TNF-, inhibited both. Anti-TNF-, had no marked inhibitory effects in the Art-r, in Lox or ICD. Combined (but not separate) neutralization of both E-selectin and VCAM-1 by antibodies suppressed LcV independent from reducing influx of PMN, proving that their sustained expression is decisive for the Shw-r and interferes with normal diapedesis. Since Loxosceles venom is known to dysregulate diapedesis and degranulation of PMN in vitro, since adherent immune complexes activate PMN at the vessel wall, and since adhesion molecules are dysregulated in the Shw-r, we suggest that LcV develops when activation of PMN coincides with vascular alterations which interfere with normal diapedesis. [source]

    Heteropolymer-mediated clearance of immune complexes via erythrocyte CR1: mechanisms and applications

    IMMUNOLOGICAL REVIEWS, Issue 1 2001
    Margaret A. Lindorfer
    Summary: Opsonization of particulate pathogens by antibodies and complement can lead to their binding to the complement receptor (CR1), specific for C3b, on primate erythrocytes (E). This process of immune adherence may play a role in immunologic defense by immobilizing bacteria and viruses, thus preventing them from leaving the bloodstream to invade susceptible tissue and organs. Immune adherence of C3b-opsonized and immune complexed pathogens to E may also facilitate their transfer to, and destruction by, fixed tissue macrophages. We have used mAbs specific for CR1 crosslinked with pathogen specific mAbs to generate heteropolymers (HP) which can bind a wide range of substrates to primate erythrocytes. Both prototype and bonafide pathogens bound to primate E via HP are handled in the circulation of non-human primates in a manner which appears to be virtually identical to the mechanism by which C3b-opsonized substrates bound to E CR1 are cleared. In this process of focused phagocytosis, Fc receptors on the phagocytic cell engage the E-bound complex, CR1 is removed by proteolysis, and the entire immune complex and CR1 are internalized while sparing the E. It may be possible to use HP to target pathogens in the bloodstream in a wide range of therapeutic applications. [source]

    Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice

    IMMUNOLOGY, Issue 2 2004
    Winston L. Hutchinson
    Summary During induction of reactive systemic amyloid A protein (AA) amyloidosis in mice, either by chronic inflammation or by severe acute inflammation following injection of amyloid enhancing factor, the earliest deposits form in a perifollicular distribution in the spleen. Because the splenic follicular localization of immune complexes and of the scrapie agent are both complement dependent in mice, we investigated the possible complement dependence of AA amyloid deposition. In preliminary experiments, substantial depletion of circulating C3 by cobra venom factor had little effect on experimental amyloid deposition. More importantly, mice with targeted deletion of the genes for C1q or for both factor B and C2, and therefore unable to sustain activation, respectively, of either the classical complement pathway or both the classical and alternative pathways, showed amyloid deposition similar to wild type controls. Complement activation by either the classical or alternative pathways is thus not apparently necessary for the experimental induction of systemic AA amyloid in mice. [source]

    Anti-polymorphonuclear neutrophil antibodies in patients with leukopenia or neutropenia

    INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1p1 2010
    N. E. RIERA
    Summary Introduction:, Immune humoral neutropenia (Np) could be the consequence of anti-polymorphonuclear neutrophil (PMN) antibodies, circulating immune complexes (CIC) and/or antibodies against myeloid precursors. Granulocyte immunofluorescence test (GIFT) and a leukoagglutination technique (LAGT) assays are recommended for its diagnosis. Methods:, Fifty adult patients with secondary Np were screened for anti-PMN. GIFT by flow cytometry from viable PMN and LAGT were employed. In addition, CIC levels, low expression of CD16b (CD16 blow), PMN phenotype and sera tumor necrosis factor-alpha (TNF-,) were also evaluated. Results:, Direct IgG-PMN binding (dir-GIFT) was positive in 16% of the patients. Antibodies against autologous PMN were detected in 32% of the samples by indirect (ind)-GIFT and demonstrated in 70% of the sera by both ind-GIFT and/or LAGT. Predominance of human neutrophil alloantigen (HNA)-1b and HNA-2 expression was confirmed. CD16blow was detected in 16% of the patient's PMN and TNF-, in 68% of sera patients. Conclusion:, Our results suggest that diagnosis of immune Np in the laboratory may be improved by focusing on patient's PMN together with the assessment of cellular markers. [source]

    Chlamydia pneumoniae and luminal narrowing after coronary angioplasty

    JOURNAL OF INTERNAL MEDICINE, Issue 1 2001
    K. J. Mattila
    Mattila KJ, Juvonen JT, Kotamäki MK, Saikku PA (Helsinki University Hospital, Helsinki; Kainuu Central Hospital, Kajaani, and National Public Health Institute, Oulu, Finland). Chlamydia pneumoniae and luminal narrowing after coronary angioplasty. J Intern Med 2001; 250: 67,71. Objectives.,Numerous studies have linked Chlamydia pneumoniae with atherosclerotic vessel disease and a trend for an association of the bacteria with restenosis after percutaneous transluminae coronary angioplasty (PTCA) has also been observed. The aim of this study was to assess the role of Chlamydia pneumoniae in the luminal narrowing taking place after PTCA. Design.,A noninterventional 6-month follow-up study. Setting.,A university hospital. Subjects.,A total of 122 patients with angiographically proven coronary heart disease (CHD) referred for PTCA. Interventions.,None. Main outcome measures.,The degree of luminal narrowing in the coronary arteries following coronary angioplasty. Results.,The levels of C. pneumoniae antibodies (IgG, IgA and IgM classes) and immune complexes were not associated with luminal narrowing after PTCA in multivariate analyses whilst smoking, plasma endothelin levels and diabetes were. The serologic parameters did not change during the follow up either. Conclusions.,These results do not support a role for C. pneumoniae in luminal narrowing following PTCA. [source]

    Hepatitis B virus markers in anti-HBc only positive individuals,

    JOURNAL OF MEDICAL VIROLOGY, Issue 3 2001
    Bernard Weber
    Abstract Isolated reactivity to hepatitis B virus (HBV) core antigen (anti-HBc) is observed relatively frequently in immunocompromised individuals, intravenous drug abusers (IVDA), and in the presence of HCV infection. The reason for the lack of HBsAg is not clear. The aim of the present study was to investigate which factors (genetic variability of S gene, low-level HBsAg, and immune complexes may be responsible for the failure of HBsAg detection with commercial HBsAg screening assays. Dilution series of two recombinant HBsAg escape mutants and dilutions of serum samples from chronic HBV carriers with multiple insertions in the a determinant and different HBsAg subtypes were tested with a highly sensitive assay that detects wild-type HBsAg (Elecsys HBsAg, Roche Diagnostics, Penzberg, Germany) and two assays that detect HBV wild-type and escape mutants (Murex HBsAg Version 3, Murex and Enzygnost HBsAg 5.0, Dade Behring, Marburg, Germany). Elecsys HBsAg showed in comparison to Murex HBsAg Version 3 and Enzygnost HBsAg 5.0 a reduced sensitivity for escape mutant detection. On the other hand, the best performance for HBsAg subtype detection was obtained with Elecsys HBsAg. In the second part of the study, a selected panel of isolated anti-HBc reactive (n,=,104) serum samples (AxSYM Core) was submitted to testing by Elecsys HBsAg, Murex HBsAg Version 3, Enzygnost HBsAg 5.0, and HBsAg detection after immune complex dissociation (ICD) and anti-HBs determination with two different assays (AxSYM Ausab and Elecsys Anti-HBs). To assess the specificity of anti-HBc test results, all the samples were tested by a second anti-HBc assay (Elecsys Anti-HBc). Quantitative HBV DNA detection was undertaken with a commercially available HBV PCR assay (Amplicor HBV Monitor). HCV infection was present in 65.4% of anti-HBc only reactive individuals. Five AxSYM Core positive samples were negative by Elecsys Anti-HBc. Overall, 15 (14.4%) AxSYM Ausab negative samples gave positive results with Elecsys Anti-HBs (median value: 21 IU/ml). No low-level HBsAg carrier was detected among the isolated anti-HBc reactive individuals with Elecsys HBsAg. There was no evidence for the presence of immune complexes. Only one sample was repeatedly reactive by the Murex HBsAg, suggesting that the a mutant form of HBsAg was responsible for the isolated anti-HBc reactivity, however neutralisation assay was not interpretable and HBV DNA PCR was negative. Fifteen (14.4%) anti-HBc only positive individuals were HBV DNA carriers with concentrations ranging from 800 to more than >4,000,000 copies of viral DNA/ml. In conclusion, the most probable explanations for isolated anti-HBc reactivity in our study group are a possible interference of HBsAg synthesis by HCV infection (65.4%) and divergence of results of anti-HBs assays (14.4%). There is no evidence for the presence of low-level HBsAg carriers and immune complexes. HBsAg mutants cannot be excluded definitively by the test strategy used in the present evaluation. J. Med. Virol. 64:312,319, 2001. © 2001 Wiley-Liss, Inc. [source]

    Lower antibody response to Porphyromonas gingivalis associated with immunoglobulin G Fc, receptor IIB polymorphism

    JOURNAL OF PERIODONTAL RESEARCH, Issue 6 2008
    Y. Honma
    Background and Objective:, Human Fc,RIIB is one of the receptors for immunoglobulin G (IgG) and suppresses the activation of B lymphocytes through cross-linking with the B cell receptor via immune complexes. This function of Fc,RIIB is essential for the negative regulation of antibody production. Our previous study has demonstrated the gene polymorphism Fc,RIIB-I232T to be associated with periodontitis. The polymorphism Fc,RIIB-232T has been reported to inhibit B-cell antigen receptor signaling more effectively compared to Fc,RIIB-232I, while other groups concluded that Fc,RIIB-232T had no ability to inhibit activatory receptors. In this study, we examined whether Fc,RIIB-I232T polymorphism would change the IgG antibody response to the periodontopathic bacteria Porphyromonas gingivalis. Material and Methods:, Forty-seven patients with periodontitis were genotyped with the direct sequencing of genome DNA. Serum IgG and specific IgG subclass levels for the sonicate of P. gingivalis and the recombinant 40 kDa outer membrane protein (OMP) were determined. Results:, No significant difference in the total IgG level and IgG response to P. gingivalis sonicate were observed between sera from Fc,RIIB-232T carriers and non-carriers. The Fc,RIIB-232T carriers revealed a significantly lower IgG2 response to P. gingivalis 40 kDa OMP compared to non-carriers (p = 0.04, Mann,Whitney U -test). Lower responses of Fc,RIIB-232T carriers were also observed in specific IgG and IgG1 levels. The Fc,RIIB-232T carriers revealed a low level of IgG2 response to P. gingivalis 40 kDa OMP, even with a high average probing pocket depth. Conclusion:, These results suggest that association of the Fc,RIIB-232T allele with periodontitis might be related to the lower levels of antibody response to P. gingivalis. [source]

    Hepatitis C virus-related extra-hepatic disease , aetiopathogenesis and management

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2004
    J. Medina
    Summary Hepatitis C virus infection is often associated with extra-hepatic manifestations, secondary to the elicitation of autoimmune reactions, generalized deposition of immune complexes and lymphoproliferative disorders. The most clearly established associations are those linking chronic hepatitis C with mixed cryoglobulinaemia (and the related glomerulonephritis and cutaneous vasculitis), as well as with the presence of autoantibodies. Less well-documented disorders include non-Hodgkin's lymphoma, thrombocytopenia, sialadenitis, thyroid disease, lichen planus, porphyria cutanea tarda, rheumatoid disorders and neurological disorders. Extra-hepatic manifestations are most frequent in patients of female sex, advanced age, long-lasting infection and cirrhosis. Optimal treatment strategies should be based on the predominant manifestation of the disease. In the case of autoimmune disorders not clearly attributable to the viral infection, corticosteroids may be the most effective option. Interferon-, alone or in combination with ribavirin may be indicated for those disorders related to immune complex deposition, such as mixed cryoglobulinaemia, although relapses of extra-hepatic signs often occur on discontinuation of treatment. In some cases, interferon-, may induce or exacerbate some extra-hepatic manifestations. [source]

    Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular disease

    MEDICINAL RESEARCH REVIEWS, Issue 1 2003
    Yasuhisa Kurogi
    Abstract Mesangial cells (MC) serve a number of functions in the renal glomerular capillary including structural support of the capillary tuft, modulation of glomerular hemodynamics, and a phagocytic function allowing removal of macromolecules and immune complexes. The proliferation of MC is a prominent feature of glomerular disease including IgA nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, and diabetic nephropathy. In experimental animal models of nephritis, MC proliferation frequently precedes and is linked to the increase of extracellular matrix in the mesangium and glomerulosclerosis. Reduction of MC proliferation in glomerular disease models by treatment with heparin, low-protein diet, or antibodies to platelet-derived growth factor (PDGF), have been shown to reduce extracellular matrix expansion and glomerulosclerotic changes. Therefore, MC proliferation inhibitors may offer therapeutic opportunities for the treatment of proliferative glomerular disease. It is also known that the MC proliferation is inhibited by many kinds of pharmacological drugs, for example, angiotensin converting enzyme (ACE) inhibitors, leukotriene D4 (LTD4) antagonists, PDGF inhibitors, matrix metalloproteinases (MMP) inhibitors, 3-hydroxy-3 methyl glutaryl-coenzymeA (HMG-CoA) inhibitors, cyclin-dependent kinases (CDK) inhibitors, and others. This review summarizes the recently reported MC proliferation inhibitors with their pharmacological properties on the basis of their chemical structures. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 1, 15,31, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10028 [source]

    Number VII Behçet's disease (Adamantiades syndrome)

    ORAL DISEASES, Issue 2 2006
    M Escudier
    Behçet's syndrome (BS; Adamantiades syndrome) is the association of the triple symptom complex of recurrent aphthous stomatitis (RAS) with genital ulceration, and eye disease (especially iridocyclitis) though a number of other systemic manifestations may also be seen. BS mainly affects young adult males, and there is an association with HLA-B5 and HLA-B51 (B5101). Features such as arthralgia and leucocytoclastic vasculitis suggest an immune-complex mediated basis, which is supported by finding circulating immune complexes and, although the antigen responsible is unidentified, heat shock proteins have been implicated. An inflammatory disorder, BS is now considered as a systemic vasculitis, characterised by a very wide spectrum of clinical features and by unpredictable exacerbations and remissions. [source]

    Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia

    PARASITE IMMUNOLOGY, Issue 6-7 2008
    E. K. MIBEI
    SUMMARY Plasmodium falciparum infection can lead to deadly complications such as severe malaria-associated anaemia (SMA) and cerebral malaria (CM). Children with severe malaria have elevated levels of circulating immune complexes (ICs). To further investigate the quantitative differences in antibody class/subclass components of ICs in SMA and CM, we enrolled 75 children with SMA and 32 children with CM from hospitals in western Kenya and matched them to 74 and 52 control children, respectively, with uncomplicated symptomatic malaria. Total IgG IC levels were always elevated in children with malaria upon enrolment, but children with CM had the highest levels of any group. Conditional logistic regression showed a borderline association between IgG4-containing IC levels and increased risk of SMA (OR = 3·11, 95% CI 1·01,9·56, P = 0·05). Total IgG ICs (OR = 2·84, 95% CI 1·08,7·46, P = 0·03) and IgE-containing ICs (OR = 6·82, OR 1·88,24·73, P , 0·01) were associated with increased risk of CM. These results point to differences in the contribution of the different antibody class and subclass components of ICs to the pathogenesis of SMA and CM and give insight into potential mechanisms of disease. [source]

    Ascaris lumbricoides infection is associated with protection from cerebral malaria

    PARASITE IMMUNOLOGY, Issue 3 2000
    Mathieu Nacher
    Following reports of increased IgE in severe malaria and hypothesizing that helminth coinfections could modify its outcome, we conducted a retrospective case,control study to establish whether helminths affect the evolution of Plasmodium falciparum malaria. Some 182 severe cases, 315 mild controls and 40 controls with circulating schizonts were examined for intestinal helminths. Comparing cerebral malaria with mild controls, Ascaris lumbricoides was associated with a protective adjusted odds ratio (OR) of 0.58 (0.32,1.03) P = 0.06, for coinfection with Ascaris and Necator americanus, OR = 0.39 (0.17,0.88) P = 0.02. Protection followed a dose,effect trend (P = 0.008). When comparing cerebral malaria cases and controls with circulating schizonts the OR was 0.25 (0.009,0.67) P = 0.006. We hypothesized that Ascaris infected patients may have had decreased cyto-adherence, possibly through endothelial cell receptor downregulation and/or decreased splenic clearance leading to the absence of selection of virulent P. falciparum strains. IgE-anti-IgE immune complexes resulting from helminth preinfection may have an important role in influencing clinical presentation of severe malaria, and in establishing malaria tolerance, through the CD23/NO pathway. [source]

    MS characterization of apheresis samples from rheumatoid arthritis patients for the improvement of immunoadsorption therapy , a pilot study

    PROTEOMICS - CLINICAL APPLICATIONS, Issue 7 2009
    Mike Kienbaum
    Abstract Identification of proteins from apheresis samples was performed by both SDS-PAGE and 2-D gel separation of eluted proteins from staphylococcal protein A-based immunoadsorption columns (Prosorba®) followed by MS peptide mass fingerprinting and MS/MS peptide sequencing on a MALDI QIT TOF mass spectrometer. MS/MS peptide sequencing was performed in conjunction with a micro reversed phase HPLC configured with an online MALDI plate-spotting device. Apheresis treatment had been performed in three patients with longstanding therapy refractory rheumatoid arthritis. 2-D gels displayed ca. 500 spots representing proteins that were eluted from the Prosorba® columns. From 54 gels, a total of 1256 protein spots had been picked and yielded in the identification of 56 non-redundant proteins without counting isoforms. Proteins from the eluates belong to five major groups comprising (i) immunoglobulins (IgG, IgA, IgM heavy and light chains; about 40% of the spots), (ii) proteins involved in coagulation, (iii) HDL/LDL-associated proteins, (iv) proteins from the complement system, and (v) acute phase proteins. MS analysis showed that the full-length C3 complement protein had been cleaved upon complement activation, presumably on the column, such that the anaphylatoxin C3a was produced and released during therapy. Our results are consistent with clinical observations on both patient responses to therapy and reported adverse events. For the first time, direct molecular information has become available to support mechanistic reasoning for the principle of function of staphylococcal protein A-based immunoadsorption therapy and for the explanation of adverse events. According to our results, removal and/or modulation of immune complexes together with complement activation can be regarded as the major events that are taking place during Prosorba® therapy. In order to avoid complement activation and induction of an inflammatory cascade, we suggest the prevention of C3a anaphylatoxin-related reactions during immunoadsorption therapy. [source]

    C1q inhibits immune complex,induced interferon-, production in plasmacytoid dendritic cells: A novel link between C1q deficiency and systemic lupus erythematosus pathogenesis

    ARTHRITIS & RHEUMATISM, Issue 10 2009
    Christian Lood
    Objective C1q deficiency is the strongest risk factor known for the development of systemic lupus erythematosus (SLE), since almost all humans with a genetic deficiency of C1q develop this disease. Low C1q serum concentration is also a typical finding in SLE during flares, emphasizing the involvement of C1q in SLE pathogenesis. Recent studies have revealed that C1q has a regulatory effect on Toll-like receptor,induced cytokine production. Therefore, we undertook this study to investigate whether C1q could regulate production of interferon-, (IFN,). Methods Peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) were stimulated with 3 known interferogenic stimuli and cultured with physiologic concentrations of C1q. IFN, production was determined by an immunoassay. Results C1q significantly inhibited PBMC IFN, production induced by RNA-containing immune complexes (ICs), herpes simplex virus (HSV), and CpG DNA. C1q also inhibited PDC IFN, production induced by ICs and CpG DNA but increased PDC IFN, production induced by HSV. The regulatory role of C1q was not specific for IFN, but was also seen for interleukin-6 (IL-6), IL-8, and tumor necrosis factor ,. We demonstrated binding of C1q to PDCs both by surface plasmon resonance interaction analysis and by flow cytometry, and we also demonstrated intracellular detection of 2 C1q binding proteins. Conclusion Our findings contribute to the understanding of why C1q deficiency is such a strong risk factor for SLE and suggest an explanation for the up-regulation of the type I IFN system seen in SLE patients. [source]

    Regulation of the interferon-, production induced by RNA-containing immune complexes in plasmacytoid dendritic cells

    ARTHRITIS & RHEUMATISM, Issue 8 2009
    Maija-Leena Eloranta
    Objective Interferon-, (IFN,) is produced in several autoimmune diseases, including systemic lupus erythematosus (SLE), and may be important in their pathogenesis. We undertook this study to investigate how IFN, production induced by RNA-containing immune complexes (ICs) in plasmacytoid dendritic cells (PDCs) is regulated. Methods Normal PDCs purified from peripheral blood mononuclear cells (PBMCs) were cocultivated with other cell populations isolated from healthy individuals or SLE patients. IFN, production was induced by RNA-containing ICs, which consisted of anti-RNP autoantibodies and U1 small nuclear RNP particles, and the effects of prostaglandin E2 (PGE2), reactive oxygen species (ROS), or the cytokines IFN,2b, granulocyte,macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), or tumor necrosis factor , (TNF,) were explored. Results Monocytes inhibited IFN, production by PDCs in PBMC cultures, while natural killer (NK) cells were stimulatory. The monocytes had little effect on IFN, production by pure PDCs but inhibited its stimulation by NK cells. Monocytes from SLE patients were less inhibitory. Exposure of PBMCs or PDCs to IFN,2b/GM-CSF increased their IFN, production. RNA-containing ICs caused production of ROS, PGE2, and TNF,, especially in monocytes. These mediators and IL-10 suppressed IFN, production in PBMC cultures, with ROS and PGE2 also inhibiting IFN, production by purified PDCs. Inhibition by all of these agents, except for ROS, was abolished by IFN,2b/GM-CSF. The inhibitory effect of monocytes was significantly counteracted by the ROS scavengers serotonin and catalase. Conclusion IFN, production induced by RNA-containing ICs in PDCs is regulated by a network of interactions between monocytes, NK cells, and PDCs, involving several pro- and antiinflammatory molecules. This should be considered when designing and applying new therapies. [source]

    Deficiency of the type I interferon receptor protects mice from experimental lupus,

    ARTHRITIS & RHEUMATISM, Issue 11 2007
    Dina C. Nacionales
    Objective Systemic lupus erythematosus (SLE) is diagnosed according to a spectrum of clinical manifestations and autoantibodies associated with abnormal expression of type I interferon (IFN-I),stimulated genes (ISGs). The role of IFN-I in the pathogenesis of SLE remains uncertain, partly due to the lack of suitable animal models. The objective of this study was to examine the role of IFN-I signaling in the pathogenesis of murine lupus induced by 2,6,10,14-tetramethylpentadecane (TMPD). Methods IFN-I receptor,deficient (IFNAR,/,) 129Sv mice and wild-type (WT) 129Sv control mice were treated intraperitoneally with TMPD. The expression of ISGs was measured by real-time polymerase chain reaction. Autoantibody production was evaluated by immunofluorescence and enzyme-linked immunosorbent assay. Proteinuria and renal glomerular cellularity were measured and renal immune complexes were examined by immunofluorescence. Results Increased ISG expression was observed in the peripheral blood of TMPD-treated WT mice, but not in the peripheral blood of TMPD-treated IFNAR,/, mice. TMPD did not induce lupus-specific autoantibodies (anti-RNP, anti-Sm, anti,double-stranded DNA) in IFNAR,/, mice, whereas 129Sv controls developed these specificities. Although glomerular immune complexes were present in IFNAR,/, mice, proteinuria and glomerular hypercellularity did not develop, whereas these features of glomerulonephritis were found in the TMPD-treated WT controls. The clinical and serologic manifestations observed in TMPD-treated mice were strongly dependent on IFNAR signaling, which is consistent with the association of increased expression of ISGs with lupus-specific autoantibodies and nephritis in humans. Conclusion Similar to its proposed role in human SLE, signaling via the IFNAR is central to the pathogenesis of autoantibodies and glomerulonephritis in TMPD-induced lupus. This lupus model is the first animal model shown to recapitulate the "interferon signature" in peripheral blood. [source]

    IK cytokine ameliorates the progression of lupus nephritis in MRL/lpr mice

    ARTHRITIS & RHEUMATISM, Issue 11 2006
    Masatake Muraoka
    Objective IK cytokine has been isolated as a factor that inhibits interferon-, (IFN,),induced expression of class II major histocompatibility complex (MHC) antigens. Aberrant expression of class II MHC antigens has reportedly been recognized in the target organs of autoimmune diseases and been associated with disease activity. In this study, we investigated whether IK cytokine can ameliorate the progression of lupus nephritis in MRL/lpr mice. Methods A truncated IK analog was prepared and transfected into a nonmetastatic fibroblastoid cell line, and then injected subcutaneously into MRL/lpr mice at ages 8 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease). Results An IK cytokine, when it was translated from methionine at position 316, acted as a secretory protein. This truncated IK cytokine (tIK) reduced IFN,-induced class II MHC expression in various cells through decreased expression of class II MHC transcription activator. Treatment of MRL/lpr mice with tIK significantly reduced renal damage as compared with control mice. A significant decrease in macrophage and T cell infiltration was found in the kidneys of tIK-treated mice, resulting in decreased production of IFN, and interleukin-2. Mice treated with tIK also showed significant reduction of anti-DNA antibodies and circulating immune complexes. A specific reduction of class II MHC expression was observed on B cells and monocytes as well as in the kidney. Conclusion We prepared a potent IK analog and demonstrated its ability to ameliorate the progression of lupus nephritis. This agent may therefore provide a new therapeutic approach for lupus nephritis. [source]