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PubMed1997

IgG glycation and function during continuous ambulatory peritoneal dialysis.

IgG in dialysate may have an important role in anti-infection mechanisms during continuous ambulatory peritoneal dialysis (CAPD). As Fc fragment oligosaccharidic chains are crucial for IgG effector functions, we have tested the hypothesis that IgG glycation might occur during CAPD and modify IgG properties. Purified normal IgG was incubated with glucose solutions of different concentrations and pH. Separation of glycated IgG was performed by affinity chromatography. Complement activation (C3c deposition) and phagocytosis by polymorphonuclear leucocytes (PMN) were studied in vitro using Staphylococcus aureus Wood (STAW) as antigen. In addition, we compared the percentages of glycated IgG in IgG purified from sera and dialysates of 12 CAPD patients. The percentage of glycated IgG after in vitro incubation of normal IgG with glucose solutions was directly proportional to glucose concentrations, incubation time and pH. Glycated IgG anti-STAW induced a higher C3c deposition than non-glycated IgG anti-STAW (C3c/IgG (mean +/- SD) 0.96 +/- 0.06 vs 0.79 +/- 0.08; P = 0.027). PMN phagocytosis was not affected by IgG glycation. The percentages of glycated IgG in dialysates of CAPD patients were greater than those in corresponding sera (5.38 +/- 2.36% vs 4.56 +/- 2.47%; P = 0.006). It is concluded that IgG glycation may take place in the peritoneal cavity during CAPD and lead to enhanced complement activation. This could explain the high degree of complement activation previously described in dialysate of CAPD patients and might theoretically result in a reduction of complement factors available in dialysate for adequate anti-infection mechanisms.

Adolescent↗
PubMed1981

Basic characteristics and evaluation of a partially automated Behring laser nephelometer for the measurement of IgG, IgA, IgM and C3c in serum.

We have evaluated a partially automated Behring laser nephelometer for the measurement of IgG, IgA, IgM and C3c in serum. The system consisted of a manual Behring laser nephelometer, an automatic cuvette carrier and a Hewlett-Packard 9815 A calculator/printer. The system could process 240 preincubated samples per h when the interval between each voltage reading was set at 15 s. Day-to-day precision was near 6%. We obtained the worst precision for the determination of IgG which requires the smallest volume of diluted sample (10 microliters). The Frigen treatment used to clarify turbid sera seems to decrease IgG and increase C3c concentrations. The addition of polyethylene glycol 6000 at a concentrations of 40 micro/L in the reaction mixture did not improve the assay ranges. Comparison studies with radial immunodiffusion for the four proteins and with the IgM - BMC Immunological Turbidity Test using either least-squares or Deming's regressions gave very good correlation figures, except for C3c and for some IgM paraproteins. We could decrease the cost per test by re-using the plastic cuvettes. The utilization of the calculator-printer greatly simplified data handling but the automatic carrier was not considered a real asset without complete automation.

Autoanalysis↗
PubMed2000

[Immunologic disturbances in patients with idiopathic posterior uveitis].

PURPOSE: This study aimed to evaluate the immune system function in patients with idiopathic posterior uveitis. MATERIAL AND METHODS: 50 patients--29 women (58%) and 21 men (42%)--were examined. Intraocular inflammation intensity was scored on standard uveitis grading system prepared by BenEzra et al. In all cases selected parameters of serum immune system activity--immunoglobulins IgA, IgG, IgM, IgE, complement proteins C3c and C4, circulating immune complexes (CIC) and autoantibodies: ANA, ANCA, ACA were detected. All immune system parameters were assessed in active stage of the disease and then 1, 3, 6, 12 months after the beginning of immunosuppressive therapy. RESULTS: Among 50 patients immunological abnormalities were found in 38 cases (76%). Changes in serum immunoglobulin concentrations were present in 28 patients and the most common pathology was the deficiency of serum IgG in 11 subjects. In 34 cases abnormalities of the complement system were present. In 43 subjects serum CIC were detected. ANA in indirect immunofluorescence test were found in 9 patients. Neither ANCA nor ACA were present in serum of this group of patients. CONCLUSIONS: Non specific abnormalities of immune system parameters found in serum of 38 patients with idiopathic posterior uveitis can indicate their role in pathogenesis of this disease. The deficiency of IgG can be related to CIC formation in this group of patients. Probably circulating immune complexes (CIC) are involved in the pathogenesis of endogenous posterior uveitis and they can act as an aggressor or protector against the retinal autoimmune mechanisms.

Adolescent↗
PubMed1993

Extended major histocompatibility complex haplotypes in celiac patients in the west of Ireland.

The highest reported prevalence of celiac disease (gluten-sensitive enteropathy) is found in the West of Ireland. Recent genetic data have suggested that major histocompatibility complex-linked loci may have a dominant genetic effect for disease susceptibility in this population compared with a recessive effect in other groups. To further understand the role of the MHC in celiac disease in the West of Ireland, we analyzed markers for 22 MHC haplotypes from celiac patients and compared them with 18 nontransmitted haplotypes found in the parents of celiac children, and with reported haplotypes from other populations. An extended MHC haplotype including [HLA-B8, DR3, DQw2, Bf*S, C4A*Q0, and C4B*1] accounted for 50% of celiac haplotypes but only 27% of nontransmitted parental haplotypes. Compared with other reported haplotypes in celiacs, patients from the West of Ireland show a higher prevalence of HLA-A1 as a component of this extended haplotype, suggesting that although the core haplotype is similar between Irish patients and others, the celiac population in the West of Ireland differs at other HLA loci. We did not observe any other common haplotypes among our patients unlike the situation in other populations. These differences may underlie the possible dominant effect of HLA-linked loci and the unusually high prevalence of celiac disease in the Irish population. We also found that the serum levels of complement components C3c, C4, and factor B were significantly lower among celiac patients than nonceliacs. The lower serum level of C4 appears to be related to the presence of deletions and null alleles at the C4A and C4B loci in celiacs.

Adult↗
PubMedDate not supplied

Humoral immunity in Nigerians with Schistosoma haematobium infection.

Circulating soluble immune complexes (CIC), immunoglobulin classes (IgG, IgA, and IgM), acute phase proteins (alpha-l-fetoprotein and alpha-1-acid glycoprotein) and complement factors (C4 and C3c) levels were determined in 52 Nigerian patients with urinary schistosomiasis (USS) and 39 healthy subjects by polyethylene glycol precipitation and single radial immunodiffusion methods respectively. A considerably higher proportion of USS patients than the controls had elevated levels of soluble immune complexes. IgM, IgA and C3c levels were significantly higher in USS patients than the controls. However, serum concentration of C4 was significantly reduced in USS patients than the controls while that of IgG was not significantly reduced in these patients. The mean levels of alpha-l-fetoprotein and alpha-l-acid glycoprotein were comparable in the USS subjects and the controls. Correlation analysis showed association between S. haematobium egg numbers with serum concentration of IgM, C3c and CIC. These observations could be the results of increased rate of CIC formation, and inflammatory responses to schistosome antigens. The study concluded that IgM associated-CIC may be responsible for the immunopathology of chronic schistosomiasis.

Adolescent↗
PubMed1982

Two-dimensional gel electrophoresis method for investigation of human plasma proteins: detection of subtle changes during filtration leukapheresis.

Special problems are associated with analysis of human plasma proteins by standard "high-resolution" two-dimensional gel electrophoresis methods in which isoelectric focusing is followed by electrophoresis in sodium dodecyl sulfate/polyacrylamide gels (SDS-PAGE). Individual plasma proteins are often separated into overlapping groups of multiple spots, and identification of individual spots is further confounded by genetic variation. Analytical recovery of components of high molecular mass is also low or variable. These problems may be reduced or overcome by use of a "low-resolution" method consisting of electrophoresis of native proteins at pH 8.6 in an agarose gel followed by SDS-PAGE without added reducing agent. About 60 proteins can be resolved, most as single spots. About 25 of these proteins have been "mapped," and tentatively identified. We have examined 119 plasma samples taken from six donors who were undergoing filtration leukapheresis and 10 donors who were undergoing centrifugation leukapheresis or plateletpheresis. In all cases, passage of blood through a nylon filter induced a significant increase in a doublet of spots tentatively identified as complement component C3c. This was detected in the effluent from the filter throughout the first 30 min of filtration, and to a lesser extent in the venous blood. These spots were not induced by the centrifugation procedures. One filtration donor also showed increased acute-phase proteins 24 h after the procedure.

Blood Proteins↗
PubMed1988

[Various immunological aspects of essential and symptomatic hypertension].

131 patients with essential hypertension (EH) and 30 patients with secondary hypertension (SH) of renal genesis were examined, all of them Russian inhabitants of Moscow, aged 20-56. In patients with EH increased rate of HLA-B13 and B22 antigens was determined. The highest rate of HLA-B13 antigen in this group was registered in patients without IHD, while patients with IHD had the highest rate of HLA-B22 antigen compared to controls. Patients with SH demonstrated no significant difference in HLA antigens distribution from that in controls. Besides, patients with EH had significantly increased serum concentration of circulating immune complexes (CIC), of IgA and beta 2-microglobulins as well as of three complement components (C3c, C4 and B factor). Similar changes were observed in patients with SH, excluding CIC and C3c, concentration of which did not differ from that in the control group. No strict dependence between the level of immunity humoral factors and presence of HLA-B13 and -B22 antigens was observed. The data gained suggest possible association of HLA system with EH development.

Adult↗
PubMed1999

Immunity to spermatozoa and male fertility.

Immunological characterization of semen and male fertility are discussed. The pH of seminal plasma is very similar in groups of fertile and infertile men. Nonspecific immunological factors such as lysozyme, C3c, alpha-1 antitrypsin and beta-2 microglobulin were significantly higher in 14% of infertile men. Seminal antibodies agglutinating spermatozoa are frequently observed in IgG and IgA isotypes. High levels of seminal anti-phospholipid antibodies in seminal plasma could influence epitopes on the endometrium, oocyte or early embryo in patients with repeated unexplained spontaneous miscarriages.

Adult↗
PubMedDate not supplied

Another look at the nephrotic syndrome in adult Nigerians: pathological and immunological findings.

One hundred and twenty adult Nigerians with the nephrotic syndrome were subjected to similar pathological investigations which included light microscopy and immunoperoxidase study of renal biopsy specimens, serum immunoglobulins and C3c levels. Histological findings showed a wide range of changes with the minimal change type of lesion and proliferative glomerulonephritis accounting each for 33.3 percent of cases studied. Focal changes accounted for 26.3 percent of cases. Glomerular immune deposits were present in 78.6 percent of cases showing non-minimal change glomerular lesions. Serum IgG and IgA were significantly depressed when compared with matched controls (P less than 0.05 and P less than 0.01 respectively) while IgM levels were significantly increased, (P less than 0.001). There was no significant difference between the mean values of serum C3c in the nephrotic group and matched control group. This study shows the high incidence of minimal change nephropathy in our adult population. Although some immunoglobulin (especially IgM) may be identified in occasional glomeruli and cause uncertainty as to the diagnosis, such minor deposition of IgM which is often non specific does not preclude a diagnosis of minimal change nephropathy.

Adolescent↗
PubMedDate not supplied

[Demonstration and differentiation of circulating immune complexes in chronic inflammatory rheumatic diseases using a semiautomated PEG-precipitation laser nephelometer test].

Circulating immune complexes were determined in rheumatoid arthritis and systemic lupus erythematosus using a semiautomated PEG-precipitation laser-nephelometer technique. Immunoglobulins IgA, IgG and IgM as well as complement proteins C3c and C4 were quantitatively determined in 2.75% PEG-precipitates. The PEG-precipitates obtained from the sera of healthy controls, SLE patients, and RA subjects displayed different protein patterns. In RA sera a significant elevation of all investigated proteins was found. In SLE sera, a significant increase of IgG, IgA, IgM, and C3 was found, whereas C4 was significantly reduced as compared to the controls. Typical values for a calculated IgG/C4 ratio in circulating immune complexes were obtained for RA and SLE. In RA this ratio remained unchanged in different activity stages and was found in seropositive as well as in seronegative sera. Thus circulating immune complexes from SLE and RA sera differ with respect to the degree of complement-dependent solubilization.

Adult↗
PubMed1998

Differences in glomerular leukocyte infiltration between IgA nephropathy and membranoproliferative glomerulonephritis.

BACKGROUND: An important aspect in glomerular nephritic processes is the enhanced influx of leukocytes into the glomerulus. METHODS: To investigate the mechanisms of intraglomerular leukocyte infiltration in IgA nephropathy (IgA-N) and membranoproliferative glomerulonephritis type I (MPGN-I), we immunohistochemically examined the intraglomerular expression of leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18), macrophage-1 (Mac-1, CD11b/CD18) and intercellular adhesion molecule-1 (ICAM-1, CD54) together with glomerular deposition of C3c and fibrinogen. RESULTS: In IgA-N (n=42), LFA-1+ cells were distributed mainly in glomeruli with intense expression of ICAM-1, and there was a positive correlation (P<0.001) between the number of LFA-1+ cells and the degree of ICAM-1 expression. Mac-1+ cells had no correlation with glomerular C3c deposition, but had a significant correlation with fibrinogen deposition (P<0.05). The number of LFA-1+ cells was significantly greater than of Mac-1+ cells (P<0.05). The number of LFA-1+ cells was strongly correlated with that of CD68+ cells (P<0.00001). In MPGN-I (n= 43), on the contrary, Mac-1+ cells correlated only with C3c deposition (P<0.001), and they were observed mainly in peripheral loops of glomerular capillaries where C3c was deposited with a similar distribution. However, there was no relationship between LFA-1+ cells and ICAM-1 expression. The number of Mac-1+ cells was greater than that of LFA-1+ cells (P<0.0001), and most Mac-1+ cells were identical to CD15+ cells. CONCLUSION: These results indicate the possibility that different mechanisms may cause glomerular leukocyte infiltration in various forms of human glomerulonephritis. The LFA-1/ICAM-1 pathway may play an important role in glomerular leukocyte infiltration in IgA-N, while the Mac-1/complement pathway may be important in MPGN-I. The former may promote mainly the infiltration of CD68+ cells, and the latter may promote that of CD15+ cells. In addition, Mac-1+ cells may act as fibrinogen and complement receptors in IgA-N and MPGN-I, respectively.

Antigens, CD↗
PubMed2000

Prevention of infection in multiple trauma patients by high-dose intravenous immunoglobulins.

OBJECTIVE: To investigate the activity of intravenous immunoglobulin (IVIG) as a prophylactic agent against infection in trauma victims. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: A 20-bed university intensive care unit. PATIENTS: Thirty-nine trauma patients with injury severity scores (ISSs) of 16-50. INTERVENTIONS: Penicillin was given at the time of admission and continued at least until day 4. Twenty-one patients received IVIG and 18 patients received human albumin at 1 g/kg in four divided doses (days 1, 2, 3, and 6). The two groups had similarities in age, gender, Acute Physiology and Chronic Health Evaluation II score, risk of death, and Glasgow Coma Scale score, but differing ISSs (p = .02), at the time of admission. Blood was collected on days 1, 4, and 7. MEASUREMENTS AND MAIN RESULTS: Clinical variables related to infection were recorded. The complement components C3c, C4 and CH50, IgG, and the fractions of IgG were measured. The serum bactericidal activity (SBA) was assessed at 37 degrees C (98.6 degrees F) and 40 degrees C (104.0 degrees F) at the time of admission and during the course of IVIG administration. Controlling for ISS, IVIG-treated patients had fewer pneumonias (p = .003) and total non-catheter-related infections (p = .04). Catheter-related infections (p = .76), length of stay in the intensive care unit, antibiotic days, and infection-related mortality did not differ between the two groups. A significantly increased trend in IgG and its subclasses was shown on days 4 and 7 in the IVIG group but not in the control group (p<.000001). No important differences were noted in complement fractions. The SBA of the groups was similar on day 1, but significantly higher on days 4 and 7 (p<.000001) in the IVIG group, remaining so controlling for complement and ISS. SBA was higher at 40 degrees C (104.0 degrees F) compared with 37 degrees C (98.6 degrees F) (p<.0001) under all three conditions. In both groups, low SBA (on days 1, 4, and 7) was associated with increased risk of pneumonia (p<.01) and non-catheter-related infections (p = .06 for day 1; p<.01 for days 4 and 7). CONCLUSIONS: Trauma patients receiving high doses of IVIG exhibit a reduction of septic complications and an improvement of SBA. Early SBA measurement may represent an index of susceptibility to infection.

APACHE↗
PubMed1993

Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor.

In septic shock, hypotension, disseminated intravascular coagulation, and neutrophil activation are related to the activation of the blood coagulation contact system. This study evaluates in dogs the effect of the C1-esterase inhibitor (C1-INH), a main inhibitor of the blood coagulation contact system, on the cardiovascular and respiratory dysfunction associated with endotoxic shock. Two groups were included: controls, which received Escherichia coli endotoxin, and a C1-INH group in which C1-INH was infused before E. coli endotoxin administration. In both groups, endotoxin produced hypodynamic shock; however, the decrease in the systolic index and the ventricular systolic work indexes were greater in controls than the C1-INH group. In controls, the arterial O2 partial pressure decreased by 30% and the alveolo-arterial O2 difference increased by 625%, these parameters remained unchanged in the C1-INH group. Hypoxemia was associated with increased intrapulmonary shunt, decreased blood coagulation contact factors, and decreased C3c. In contrast, C1-INH administration prevented endotoxin-induced hypoxemia, the increase in intrapulmonary shunt, and the decrease in blood coagulation contact factors. This study shows that, in dogs with endotoxic shock, pulmonary dysfunction is associated with an activation of the blood coagulation contact phase system. An inhibition of this system by C1-INH prevented the hypoxemia induced by endotoxic shock.

Animals↗
PubMed1997

Immunoglobulin and C3-activator profile of the microbiology laboratory worker.

The levels of immunoglobulin, C3-Activator and C3c in the sera of members of staff who have been continuously engaged for upwards of 10 years in the microbiological routine laboratory of a teachings hospital were determined. These were compared with the local normals, with those of the junior members of staff in the same laboratory but who had put in less than 5 years continuous service and with a control group. The means in all five determinations were much higher in the senior members of staff than the normal standards of the area, particularly the IgG, which was almost double the local normals. The levels for the junior staff were on the whole slightly higher than the control group. The increase in the levels of immunoglobulins with corresponding increases in C3-Activator and 3Cc suggest that immunological reactions, with the binding of complement in the alternate and classical pathways of activation are taking place in most of these senior workers. In the absence of any manifest illness in the senior staff, the findings may suggest a high degree of immunological protection.

Adult↗
PubMed1979

Studies on human filariasis in Malaysia: immunoglobulin and complement levels in persons infected with Brugia malayi and Wuchereria bancrofti.

Levels of immunoglobulins G, A, M and E as well as complement components C3c and C4 have been determined in populations in various endemic areas in Peninsular Malaysia and also in filariasis patients. High immunoglobulin levels were seen. In the microfilarial-negative group IgG was 2009 mg% while IgE was 3967 I.U./ml. In the filariasis group, Wuchereria bancrofti patients had significantly higher levels of IgG, IgM and IgE, namely, 3314 mg%, 804 mg% and 18400 I.U./ml respectively. The significance of these levels is discussed.

Adolescent↗
PubMed1987

A solid-phase anti-C3 assay for detection of immune complexes in six distinguished forms.

A solid-phase anti-C3 assay detecting immune complexes associated with C3 fragments is described. Two monoclonal antibodies against C3 fragments are used; one recognizes an epitope expressed on C3b, C3c and C3i, the other recognizes an epitope expressed on C3dg and iC3b. Combining these monoclonal anti-C3s with antibodies against class-specific immunoglobulins in enzyme-linked immunosorbent assay (ELISA), immune complexes (ICs) are detected in six distinguished forms; C3b-IgG-IC, iC3b/C3dg-IgG-IC, C3b-IgA-IC, iC3b/C3dg-IgA-IC, C3b-IgM-IC and iC3b/C3dg-IgM-IC. About three-fourths of the plasma samples from patients with active SLE or IgA-nephritis were found positive in one or more types of ICs. IgA-type ICs were found very frequently in patients with autoimmune or renal diseases.

Antibodies, Monoclonal↗
PubMed2001

Growth of Plasmodium falciparum induces stage-dependent haemichrome formation, oxidative aggregation of band 3, membrane deposition of complement and antibodies, and phagocytosis of parasitized erythrocytes.

Plasmodium falciparum-parasitized erythrocytes (RBCs) are progressively transformed into non-self cells, phagocytosed by human monocytes. Haemichromes, aggregated band 3 (Bd3) and membrane-bound complement fragment C3c and IgG were assayed in serum-opsonized stage-separated parasitized RBCs. All parameters progressed from control to rings to trophozoites to schizonts: haemichromes, nil; 0.64 +/- 0.12; 5.6 +/- 1.91; 8.4 +/- 2.8 (nmol/ml membrane); Bd3, 1 +/- 0.1; 4.3 +/- 1.5; 23 +/- 5; 25 +/- 6 (percentage aggregated); C3c, 31 +/- 11; 223 +/- 86; 446 +/- 157; 620 +/- 120 (mOD405/min/ml membrane); IgG, 35 +/- 12; 65 +/- 23; 436 +/- 127; 590 +/- 196 (mOD405/min/ml membrane). All increments in rings versus controls and in trophozoites versus rings were highly significant. Parasite development in the presence of 100 micromol/l beta-mercaptoethanol largely reverted haemichrome formation, Bd3 aggregation, C3c and IgG deposition and phagocytosis. Membrane proteins extracted by detergent C12E8 were separated on Sepharose CL-6B. Haemichromes, C3c and IgG were present exclusively in the high-molecular-weight fractions together with approximately 30% of Bd3, indicating the oxidative formation of immunogenic Bd3 aggregates. Immunoblots of separated membrane proteins with anti-Bd3 antibodies confirmed Bd3 aggregates that, in part, did not enter the gel. Immunoprecipitated antibodies eluted from trophozoites reacted preferentially with aggregated Bd3. Changes in parasitized RBC membranes and induction of phagocytosis were similar to oxidatively damaged, senescent or thalassaemic RBC, indicating that parasite-induced oxidative modifications of Bd3 were per se sufficient to induce and enhance phagocytosis of malaria-parasitized RBC.

Animals↗
PubMed1998

Acute phase and opsonin response in cardiac surgery patients: influence of underlying cardiac disease.

Cardiopulmonary bypass (CPB) leads to an activation of plasma cascade systems, complement activation, and an acute phase response. To evaluate the influence of the underlying cardiac disease on the activation pattern of these systems, we compared inflammatory changes in coronary artery bypass grafting (CABG) patients with patients undergoing aortic valve replacement. We investigated changes of the acute phase proteins alpha 1-proteinase inhibitor and fibrinogen, the unspecific opsonin fibronectin, and the complement components C3c and C4 induced by extracorporeal circulation in 12 patients undergoing aortic valve replacement and in 12 patients undergoing CABG. Concentrations of C3c and C4 decreased in both groups after the onset of CPB and C4 concentration remained below post-induction levels up to 24 h after onset of CPB (p = 0.04). Fibronectin levels dropped immediately before the onset of CPB (p = 0.01), reaching the lowest values after 20 min of extracorporeal circulation. Fibrinogen and alpha 1-proteinase inhibitor levels after induction of anaesthesia were significantly higher in the CABG group and remained higher throughout the entire study period (p < 0.001). As an indicator of a postoperative acute phase response, concentrations of both proteins rose in the postoperative period above post-induction levels (p < 0.02).

Acute-Phase Reaction↗