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Mannan-binding protein and bovine conglutinin mediate enhancement of herpes simplex virus type 2 infection in mice.

A broad range of plant lectins have recently been shown to inhibit the infectivity of herpes simplex virus type 1 (HSV-1) in vitro. We decided to investigate the role of mammalian lectins in infection with herpes simplex virus. Two lectins, conglutinin and mannan-binding protein (also called mannose-binding protein, MBP), belonging to the collectin family of lectins, were examined. Four week-old BALB/c mice were injected subcutaneously with 100 micrograms bovine conglutinin or 50 micrograms human MBP 1 day before intravenous infection with 5 x 10(4) PFU of herpes simplex virus type 2 (HSV-2). A three-fold increase in virus titre of the liver was observed on day 3 of the infection in the mice pretreated with conglutinin or MBP, whereas no effect was seen on days 1 and 5. In a standard plaque assay using Vero cells we were not able to demonstrate reproducibly either infection inhibition or infection enhancement, when virus was pre-incubated with differing concentrations of the collectins. The concentrations used were similar to those used by us in vivo, and by others in in vitro experiments showing inhibition of the infectivity of HSV-1 with plant lectins. In an ELISA with HSV-2 antigens captured on anti-HSV-2 antibodies, calcium-dependent and carbohydrate inhibitable binding of the collectins was observed. Our results indicate that the effect of endogenous mammalian collectins in vivo may not be neutralization as suggested by the data using plant lectins. Instead, the previously described opsonizing activity of the mammalian collectins may provide the virions with an alternative port of entry into cells leading to infection enhancement.

Animals↗

Subclass distribution of IgA and IgG antibodies against Clq in patients with rheumatic diseases.

To obtain insight into the immunoregulatory mechanisms in patients with different rheumatic diseases, the occurrence and the subclass distribution of IgA and IgG antibodies against Clq (anti-ClqAb) was determined. In patients with systemic lupus erythaematosus (SLE) the highest frequency of increased serum levels of IgG anti-ClqAb were found, whereas IgA anti-ClqAb were predominantly present in patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis complicated by vasculitis (RV). In all the IgA anti-ClqAb positive AS and RV patients the antibody reactivity involved the IgA1 subclass while the IgA2 subclass was found in 47% of the patients. Further characterization of the IgA anti-Clq binding activity in sera of AS patients revealed that both subclasses of IgA anti-ClqAb were predominantly polymeric; the binding of both IgA subclasses with solid phase Clq was inhibitable by aggregated fluid phase Clq; we found no detectable interference of rheumatoid factor in the test system for the measurement of IgA anti-ClqAb. In patients with SLE the IgG anti-ClqAb reactivity was mainly of the IgG2 and IgG3 subclass, whereas in the same patients the IgG anti-tetanus toxoid response was not restricted to these subclasses. The predominance of IgG2 and IgG3 subclass of anti-ClqAb in sera of SLE patients, suggests a skewing of the anti-ClqAb response. The observation that the IgA anti-ClqAb of both subclasses is predominantly polymeric in nature and the notion that polymeric IgA is associated with activation of inflammation cascades, suggests that IgA anti-ClqAb may contribute to tissue damage.

Antibodies, Monoclonal↗

Antineutrophil cytoplasmic antibodies (ANCA) in idiopathic pulmonary hemosiderosis.

Four children were diagnosed with idiopathic pulmonary hemosiderosis (IPH), over a period of 4 years. Retrospectively, antineurtrophil cytoplasmic antibodies (ANCA) were studied by indirect immunofluorescence (IIF) and ELISA in 18 sera from these patients, stored at -20 degrees C. ANCA-positive sera, from 1/20 to 1/1, 200 dilution, were found in 3/4 of the patients, by IIF. The patient with the highest titre of ANCA died 3 months later during an acute crisis, the other two patients need a minimal dose of steroids. In one case only, a patient who is still without treatment, had no ANCA. The antibodies anti-myeloperoxidase and anti-proteinase-3 were negative or at border line levels. Rheumatoid factor, antinuclear (Hep-2), anti-endomysial, anti-reticulin and antibasement membrane antibodies were negative in all sera. The surviving patients were followed-up for more than 10 years with no systemic or renal disease appearances. The presence of serum ANCA may help to classify children with pulmonary haemorrhage and may have a prognostic value.

Antibodies, Antineutrophil Cytoplasmic↗

Plasma exchange in rheumatoid vasculitis.

Vasculitis is an uncommon, extremely debilitating complication of severe, chronic rheumatoid arthritis. High levels of circulating immune complexes along with vascular deposition of immunoglobulins and complement indicate an immune complex mediated disease. No pharmacologic therapy has been completely effective and the incidence of mortality is exceptionally high. This study shows clinical improvement with combination of plasma exchange and cytoxan therapy. We report an association in the conspicuous decline of immune complexes with objective clinical remission in 2 patients who underwent combination therapy. This adjunctive combination therapeutic modality is recommended in the treatment of rheumatoid vasculitis.

Aged↗

Intravenous gammaglobulin therapy in idiopathic thrombocytopenic purpura. Results with the Netherlands Red Cross immunoglobulin preparation.

The effect of high-dose intravenous gammaglobulin (IVG) therapy with a CLB preparation was studied in 42 patients: 8 patients had acute and 26 patients had chronic idiopathic thrombocytopenic purpura (ITP); 5 patients had thrombocytopenia accompanied by various diseases such as systemic lupus erythematosus, auto-immune haemolytic anaemia and neutropenia; 3 patients had hypoplastic anaemia and 1 patient had neutropenia and rheumatoid arthritis. After treatment, a rise in platelet count occurred in about 75% of the patients with ITP, although there was no sustained response in any of the patients. There was no correlation between the strength of platelet antibodies as detected by the direct immunofluorescence test before infusion and the pattern of response to the infusion. In most cases of ITP, no immune complexes, as measured by Clq-binding assay, were observed. Furthermore, we found no relationship between the amount of Clq-binding activity of patients' sera and the reaction pattern after infusion of IVG. Splenectomy of the patient had no influence on the outcome of IVG therapy.

Adult↗

Treatment of AB deficiencies.

The objective of this study was to compare serum immunoglobulin levels and the clinical status of patients with primary immune deficiency who received an intravenous immunoglobulin (IVIG) (pH 4.0) preparation for 1 year with results previously obtained when the same patients received intramuscular immunoglobulin (IMIG). During the IVIG treatment year, increased serum immunoglobulin levels, shorter duration of certain infectious disorders, reduced antibiotic use, ans improved rheumatoid symptoms were observed. The actual benefit of IVIG therapy could not be established until after the sixth months, since illness was even further reduced during the second 6 months of treatment. Other clinical observations are evaluated in the 2 groups.

Anti-Bacterial Agents↗

Opsonic and physicochemical characteristics of intravenous immunoglobulin preparations.

The composition and opsonizing activity of five commercially available immunoglobulin preparations for intravenous use (Venoglobulin I, Venilon, Gammagard, Polyglobin, and Sandoglobulin) were studied. The composition of these preparations does not differ very much as far as total protein, immunoglobulin class and IgG subclass concentrations are concerned. The only exceptions were that Veniglobulin I, Gammagard and Sandoglobulin contain IgA, which might cause side effects in patients with anti-IgA antibodies, Gammagard contains very little IgG4, and Venilon and Polyglobin contain no and almost no IgG3, respectively, which might explain their very low opsonic activity. It was found that Venilon and Gammagard activate complement in the ready-for-infusion state. The opsonic activity of Venoglobulin I, Sandoglobulin and Gammagard is about equal to that of inactivated serum: Staphylococcus aureus, Escherichia coli with K antigen, Streptococcus pyogenes and Streptococcus group B are well opsonized and E. coli without K antigen and Streptococcus pneumoniae are poorly opsonized.

Blood Bactericidal Activity↗

Immune complexes in acute pancreatitis.

Immune complexes were detected in the sera of ten of 22 patients with acute pancreatitis using a Clq deviation assay. Five of these were positive using a second technique. There was no correlation between immune complexes and clinical or aetiological features of the pancreatitis. Two patients with immune complexes developed a benign and transient pancreatic polyarthritis. Immune complexes may provide one common path in the sequence of pathogenic events that lead to pancreatitis.

Acute Disease↗

Complement-binding antibodies to Aspergillus fumigatus in patients with pulmonary aspergillosis.

Complement-binding antibodies against Aspergillus fumigatus were determined by a fluorescent antibody technique with purified human Clq as the source of complement. Clq binding aspergillus antibodies were found in 8 (67%) of 12 patients with pulmonary aspergillosis, in 4 (57%) of 7 patients with suspected pulmonary aspergillosis, in one (14%) of 7 patients with precipitating antibodies to A. fumigatus of undetermined clinical significance, and in 4 (7%) of 54 healthy blood donors. Sera from patients with definite or probable aspergillosis produced an immunofluorescent staining of hyphal cytoplasm, whereas the staining obtained with positive donor sera was confined to hyphal walls. A positive correlation was found between the frequency and titres of Clq binding antibodies and titres of IgG and IgM aspergillus antibodies. Clq binding antibodies were found only in sera with an IgG aspergillus antibody titre greater than or equal to 640. The frequency of Clq binding antibodies in sera with IgG titres greater than or equal to 640 was significantly higher in patients with aspergillosis (67%) than in blood donors (16%) (p = 0.0036). The Clq binding antibody test may provide diagnostic information as well as clues to the pathogenesis of aspergillus lung disease.

Adolescent↗

Sera of patients with high titers of immunoglobulin G against Toxoplasma gondii induce secretion of tumor necrosis factor alpha by human monocytes.

Toxoplasma gondii alone does not induce tumor necrosis factor alpha (TNF-alpha) secretion by human monocytes and macrophages. Nevertheless, sera from infected patients with high titers of specific immunoglobulin G antibodies against T. gondii induce TNF-alpha secretion, which is significantly higher than the corresponding induction by negative sera (P less than 0.05). After incubation with the positive serum, parasites also induce secretion of this cytokine, but TNF-alpha levels are lower (11.4 to 71.8%) than those obtained with positive serum alone. Therefore, this secretion seems to be elicited in part by antibody-T. gondii complexes and/or another unidentified factor(s), probably different from lipopolysaccharide, interleukin-1, TNF-alpha, and gamma interferon. In this study, monocytes secreted more TNF-alpha into the culture fluid than macrophages did (P less than 0.05), and no correlation was observed between secretion of this cytokine by the monocytes and the intracellular multiplication of the parasites, evaluated by [3H]uracil incorporation. Sera from patients with other infections diseases did not induce secretion of TNF-alpha; however, serum free of antibodies to T. gondii, obtained from patients with leishmaniosis, also stimulated secretion of the cytokine.

Animals↗

Evaluation of a Cordia-IC enzyme-linked immunosorbent assay kit for the detection of circulating immune complexes.

A commercial kit (Cordia-IC) from Cordis Laboratory, Miami, Fla., was compared with the Raji cell radioimmunoassay for its ability to detect circulating immune complexes (CIC) in sera from 30 control subjects and 118 patients with infectious diseases. The 118 patients were categorized into the following groups: (i) 23 patients with bacterial endocarditis, (ii) 41 patients with bacteremia from an infected intravascular catheter or access device, and (iii) 54 patients with Staphylococcus aureus bacteremia related to a deep tissue infection. The Cordia-IC was comparable to the Raji cell radioimmunoassay in intraassay variability (4.0 versus 8.0%) and interassay reproducibility (8.7 versus 20.0%). Neither assay found CIC amounts above 12.5 micrograms equivalents (eq) of aggregated human gamma globulin (AHG) per ml in any of the 30 control individuals. In group 1, Cordia-IC detected 19 of 23 positives (mean, 73.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 23 positives (mean, 54.8 micrograms eq of AHG per ml). In group 2, Cordia-IC detected 19 of 41 positives (mean, 20.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 41 positives (mean, 15.1 micrograms eq of AHG per ml). In group 3, Cordia-IC found 38 of 54 positives (mean, 28.0 micrograms eq of AHG per ml), whereas the Raji cell found 32 of 54 positives (mean, 23.9 micrograms eq of AHG per ml). Statistically, these findings were not significantly different in any of the three patient groups (P> 0.15), and there was an overall good correlation between the results obtained by the two assays (r+0.64, P<0.001). The Cordia-IC provided a suitable assay for the detection of CIC and might find application in routine clinical laboratories.

Antigen-Antibody Complex↗

SOCS1 and SOCS3 are targeted by hepatitis C virus core/gC1qR ligation to inhibit T-cell function.

T cells play an important role in the control of hepatitis C virus (HCV) infection. We have previously demonstrated that the HCV core inhibits T-cell responses through interaction with gC1qR. We show here that core proteins from chronic and resolved HCV patients differ in sequence, gC1qR-binding ability, and T-cell inhibition. Specifically, chronic core isolates bind to gC1qR more efficiently and inhibit T-cell proliferation as well as gamma interferon (IFN-gamma) production more profoundly than resolved core isolates. This inhibition is mediated by the disruption of STAT phosphorylation through the induction of SOCS molecules. Silencing either SOCS1 or SOCS3 by small interfering RNA dramatically augments the production of IFN-gamma in T cells, thereby abrogating the inhibitory effect of core. Additionally, the ability of core proteins from patients with chronic infections to induce SOCS proteins and suppress STAT activation greatly exceeds that of core proteins from patients with resolved infections. These results suggest that the HCV core/gC1qR-induced T-cell dysfunction involves the induction of SOCS, a powerful inhibitor of cytokine signaling, which represents a novel mechanism by which a virus usurps the host machinery for persistence.

Carrier Proteins↗

Platelet releasing activity in sera of patients with rheumatoid vasculitis.

Platelet releasing activity was found in sera fractionated by 30% ammonium sulphate in seven of 11 patients with systemic rheumatoid vasculitis, two of 16 patients with cutaneous rheumatoid vasculitis, and three of 18 patients with clinically uncomplicated rheumatoid arthritis. Serial studies in three patients suggest a key role of platelet activation by serum factors in the pathogenesis of systemic rheumatoid vasculitis. IgG rheumatoid factor or IgG containing immune complexes, or both, may be responsible for this platelet releasing activity.

Arthritis, Rheumatoid↗

Synovitis associated with serum IgM rheumatoid factor arising spontaneously in 'Old English' rabbits.

This paper reports the spontaneous development of synovitis in 'Old English' rabbits concurrent with serum IgM rheumatoid factor. Female rabbits developed lesions at a higher incidence than males (42% compared with 17%) and the pathology was of a more severe nature. In the female rabbits synovitis was associated with concurrent high serum IgM rheumatoid factor and high serum antibody levels to Pasteurella multocida. There was no histological evidence that the joints were directly infected.

Animals↗

Complement mediated inhibition of immune precipitation in rheumatoid arthritis: studies on interaction of heat aggregated IgG with IgM rheumatoid factor.

Serum samples from patients with seropositive rheumatoid arthritis contain an inhibitor of complement mediated inhibition of immune precipitation (CMIP). This inhibitory effect can be produced by the addition of either purified monoclonal or polyclonal IgM rheumatoid factor (RF) to human serum. The specificity of the rheumatoid factor influences the degree of inhibition, and when precipitation occurs the rheumatoid factor coprecipitates with the antigen-antibody complex. In rheumatoid sera there was a significant positive correlation between IgM RF concentration and inhibitory activity, though the range of inhibitory activity seen for the same concentration of rheumatoid factor was considerable. Small quantities of heat aggregated IgG (HAGG) had a much greater effect on the measurement in an enzyme linked immunosorbent assay (ELISA) of IgM RF than they did on the inhibitory activity of IgM RF in the CMIP assay. Larger quantities of HAGG initiated complement activation and increased the precipitation of immune complexes. IgM RF reduced the complement activating properties of HAGG by reducing the amount of Clq which bound to the aggregate. The mechanisms by which IgM RF overcomes CMIP in rheumatoid sera may involve its inhibitory effects on the binding of Cl to the antigen-antibody complex.

Antigen-Antibody Complex↗

Circadian variation in disease activity in rheumatoid arthritis.

Disease activity in rheumatoid arthritis as measured by repeated estimation of joint pain, stiffness, articular index, and grip strength was shown to have a circadian rythm, maximal activity being seen between 0200 and 0400 and minimal activity in the early afternoon. This variation in disease activity may be related to circadian alterations in immune and inflammatory responses (such as immune complexes and neutrophil function) dependent on alterations in circulating concentrations of steroids. The circadian variation in disease activity has important implications in assessment of patients, prescription of drugs, and performance of drug trials.

Adult↗