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PubMed1988

Protective mechanism of the immune response to a ribosomal vaccine from Pseudomonas aeruginosa. II. In vitro bactericidal and opsonophagocytic studies with specific antiserum.

In vitro bactericidal and opsonophagocytic assays were performed with mouse antiserum to a ribosomal vaccine from Pseudomonas aeruginosa. The results obtained demonstrated that both specific antibody and complement are required for bactericidal and opsonic activities. C4-deficient complement also supported these activities. Polymorphonuclear leukocytes (PMNL) are not required, but when present, augment the observed killing activity. Opsonic and bactericidal activities were found to increase with increasing complement concentrations in an apparently logarithmic fashion until maximal activity was obtained. On the contrary, determination of bactericidal activity as a function of specific antiserum concentration revealed a "prozone" effect; i.e., maximal activity was obtained at an intermediate concentration of antiserum with significantly decreased activity at both higher and lower concentrations. This effect was not observed when immunoglobulin G (IgG) purified from specific antiserum by a method involving exposure to pH 9.0 and pH 3.0 was used instead of whole antiserum. In this case bactericidal activity increased as IgG concentration was increased, also in an apparently logarithmic manner.

Animals↗
PubMed1996

IFN-gamma up-regulates expression of the complement components C3 and C4 by stabilization of mRNA.

We investigated the mechanisms underlying the regulation of complement genes C3 and C4 by IFN-gamma. IFN-gamma (500 U/ml, 24 h incubation) increased steady state mRNA levels for both C3 and C4 in three different cell types (Hep G2, U937, and primary fibroblasts). The response to IFN-gamma in Hep G2 cells was time and dose dependent. At all doses of IFN-gamma and at all incubation times, the transcription rate for these two genes, determined by nuclear run-on assays, was reduced (0.3 +/- 0.1; unstimulated rate = 1.00). The t1/2 of mRNA for C3 and C4 in unstimulated cells was 1.8 +/- 0.3 and 2.2 +/- 0.2 h, respectively. After high-dose IFN-gamma stimulation, both C3 and C4 mRNA levels remained at 100% with respect to baseline at 5 h, but after 12 h, levels fell to 13 +/- 2% (C3) and 8 +/- 3% (C4) of baseline values, giving a half-life for these mRNA species of between 5 and 12 h. IFN-gamma stimulation increased C3 and C4 protein synthesis measured at 24 h. We suggest that it is the increase in mRNA stability that is the major effector mechanism by which IFN-gamma regulates C3 and C4 gene expression.

Cell Line↗
PubMed1987

Immunoglobulins (IgG, IgA, IgM, IgE) and complement components (C3, C4) in nephrotic syndrome due to minimal change and other forms of glomerulonephritis, a clue for steroid therapy?

Serum IgG, IgA, IgM, IgE, C3 and C4 were measured in 13 patients with minimal change (MC) glomerulonephritis and 10 with the nephrotic syndrome (NS) due to other forms of glomerulonephritis. The tests were repeated in all patients with MC glomerulonephritis when they went into remission. Serum IgG was reduced, IgM, IgE and C3 were raised while serum IgA was within the normal range when the patients were nephrotic. Changes in serum immunoglobulins and complement components were not specific to MC glomerulonephritis and these parameters reverted towards normal when the NS went into remission. Elevated C3 levels probably reflected increased hepatic protein synthesis since C3 correlated significantly with serum cholesterol. There was a tendency for serum IgE concentrations to positively correlate with the total dose of prednisolone required to bring the NS to remission.

Adolescent↗
PubMed1983

Synthesis of the complement factors C3 and C4 within the central nervous system over the course of aseptic meningitis.

The concentrations of complement factors C3 and C4 were quantified by single radial immunodiffusion in unconcentrated cerebrospinal fluid (CSF) and in serum from 38 patients up to 2 months after onset of acute aseptic meningitigs (AM). Elevated absolute concentrations were found in CSF in 26 and 35 patients, respectively, and in serum in 8 and 31, respectively. Elevation of the CSF C3 index, equal to (CSF/serum C3):(CSF/serum albumin), and of the corresponding CSF C4 index were found in 16 and 7 patients, respectively, as evidence of intrathecal synthesis. Only minor differences of the frequencies of elevated CSF C3 and C4 indices were encountered over the course of AM up to 2 months after onset. The occurrence of intrathecal C3 and C4 synthesis in AM is proposed as reflecting activation of hitherto unknown significance within the central nervous system.

Adolescent↗
PubMed1987

[IgG, IgM, IgA, secretory IgA and the complement components C3, C4 and C9 in the large intestine in nonspecific ulcerative colitis and Crohn disease].

The immunohistological study of the large intestines excised from 20 patients with ulcerous colitis and Crohn's disease was made with the use of the indirect immunofluorescence test. A considerable increase in the number of IgG immunocytes has been noted in the lamina propria of the mucous membrane, especially in infiltrations around ulcers. In cases of a highly active inflammatory process accompanied by the pronounced destruction of the epithelium, IgG and C3, C4, C9 were detected in the epithelium of crypts and in blood vessels of the mucous membrane and the submucosa. One-third of the patients showed a decrease in the number of crypts with secretory and serum IgA. The authors suggest that immune complexes take part in maintaining the chronic inflammatory process.

Colitis, Ulcerative↗
PubMed1989

Differences in the metabolism of C4 isotypes in patients with complement activation.

The metabolism of the C4 allotypes C4A3,B1 and C4A3,BO was studied in five healthy control subjects and six patients with active immunological disease (five with systemic lupus erythematosus and one with rheumatoid arthritis). The specific aim was to identify any differences in the metabolism of C4A and C4B gene products that may be linked to their documented functional differences in vitro. The fractional catabolic rate of C4A3,B1 in patients was significantly greater than that of C4A3,BO (3.98 +/- 1.37 versus 3.31 +/- 0.85%/h; mean +/- s.d.; P less than 0.05) but there was no difference in control subjects (1.95 versus 1.99%/h). The extravascular:intravascular (EV:IV) distribution ratio of C4A3,B1 was also greater in both patients (1.19 +/- 0.36 versus 0.97 +/- 0.35; P less than 0.01) and controls (0.43 +/- 0.11 versus 0.31 +/- 0.13; P = 0.01). We conclude that C4B1 was catabolized more rapidly than C4A3 in patients with pathological complement activation but not in control subjects. This difference could reflect the relatively greater extravascular distribution (i.e. EV:IV ratio) of C4B at sites of immune complex deposition or, alternatively, different rates of catabolism of inactive C4 isotypes (iC4b).

Alleles↗
PubMed1975

Behaviour of synovial complement C3 and C4 components in inflammatory and degenerative joint diseases, before and after synoviorthesis.

The synovial fluid beta1a (C3) and beta1e (C4) expressed by their ratio to corresponding serum concentrations) were studied in 31 cases of seropositive rheumatoid arthritis (RA+), 5 cases of seronegative rheumatoid arthritis (RA-1), and 15 cases of osteoarthrosis (OA) before osmic acid synoviorthesis on knees. This was repeated after synoviorthesis in the synovial fluid (SF) of 24 RA+, 4 RA-, and 10 OA patients. The following studies were undertaken: (a) the relationship between these components; (b) their correlation with the SF protein concentration and rheumatoid factor titre, when present. This analysis led us to the following conclusions. (1) Before synoviorthesis (a) The SF beta1e is significantly lower than beta1a in RA+. In OA, an inverse phenomenon is observed. (b) The concentration of beta1a and beta1e are proportional to the protein concentration in the SF of OA. A significant inverse relationship between beta1a, beta1e, and the titre of rheumatoid factor is found. (2) after synoviorthesis the same studies performed on knees at the time of one or more relapses shows that the same pathogenetic process is involved and that the immunological mechanism is little influenced by this treatment. In OA also the relapse differs very little from the initial process observed before synoviorthesis.

Arthritis, Rheumatoid↗
PubMed1993

Serum complements. Inappropriate use in patients with suspected rheumatic disease.

BACKGROUND: The diagnostic value of serum complement testing is well established in inherited complement deficiencies and glomerulonephritis. Their utility is less certain in diagnosing rheumatic diseases. We noted that complement tests were frequently ordered for patients who were referred to our rheumatology clinic. We sought to determine the clinical rationale for ordering complement tests in our hospital and the effect of the test results in patients with rheumatic diseases. METHODS: We conducted a retrospective medical chart review of patients who had serum complement tests ordered at our hospital. We determined whether the test was ordered as a diagnostic tool in a patient with a suspected rheumatic disease. In these cases, we attempted to correlate the results of the complement tests with the patient's eventual diagnosis. RESULTS: We obtained the medical charts of 130 patients who had 307 complement assays (C3, C4, or total hemolytic complement) performed between October 1988 and July 1989. The tests were ordered for diagnostic reasons in 68% of the patients; 54% of these were ordered by nonspecialists. The complement tests were ordered on 28 patients with suspected rheumatic diseases. The three patients with hypocomplementemia did not have a connective tissue disease. The 10 patients who eventually were diagnosed as having rheumatic disease all had normal serum complement levels. Additionally, we found that 77% of patients had more than one complement assay ordered. The test results were discordant in only 24% of these cases. CONCLUSION: Complement screening is not a useful diagnostic test in most patients with suspected rheumatic disease. Despite their lack of established diagnostic value, these tests were frequently performed in our hospital. Judicious use of complement testing would provide substantial cost savings without a loss of clinically relevant information. When the complement testing is clinically indicated, clinicians should consider using a single C3 assay initially rather than multiple assays unless a hereditary deficiency is suspected.

Adolescent↗
PubMed1989

Role of serum complement, immunoglobulins, and cell-mediated immune system in the pathogenesis of spontaneous bacterial peritonitis (SBP).

Spontaneous bacterial peritonitis (SBP) is a common complication of advanced liver disease, which has a reported prevalence of between 4 and 27%. Frequent bacteremias due to inadequate host defense mechanisms, particularly the reticuloendothelial system (RES), with seeding of an ascitic fluid that lacks a normal opsonic activity, is believed to be the principal cause of SBP. Little data exist as to the role of serum levels of complement and immunoglobulins as well as the cell-mediated immune system in the pathogenesis of SBP. The aim of this study was to determine the serum levels of the third and fourth components of complement (C3, C4), total hemolytic complement activity (CH100), and properdin factor B (PFB) and immunoglobulins G, A, and M and various T-cell parameters in individuals admitted to hospital with ascites and advanced liver disease and to determine whether one or more of these factors could be used to predict the development of SBP in patients with advanced liver disease. Fourteen consecutive patients (nine male and five female; age 47.5 +/- 3.1 years, mean +/- SEM) with end-stage liver disease and ascites, who were evaluated for possible liver transplant at the University of Pittsburgh and who developed SBP, comprised the study group. The diagnosis of SBP was determined by positive ascitic fluid culture (three patients) and/or ascitic fluid neutrophil count of greater than 250 cells/mm3 (all patients). The control group consisted of 14 patients, matched for type of liver disease, age, and sex, who did not develop SBP.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗
PubMed2006

Down-regulated expression of complement factor I: a potential suppressive protein for gastric cancer identified by serum proteome analysis.

BACKGROUND: Screening tests are needed for gastric cancer. In order to find serologic biomarkers for gastric cancer screening, we used proteomics to search for protein biomarkers that may be detected in serum of gastric cancer patients. METHODS: Four groups of serum samples (from 20 gastric cancer patients) included pTNM stages I to IV were compared with two control groups of serum samples. The serum samples were first chromatographed using an immunoaffinity column to selectively remove albumin and IgG. Then serum proteins separated by 2-DE and identified by MALDI-TOF/TOF-MS. RESULTS: There were 3 proteins including complement C4-B precursor, complement factor I (CFI) precursor and haptoglobin precursor were found significantly different between the healthy and gastric cancer patients. Further validation study by Western blot showed that the detection of CFI precursor was under-expressed in gastric cancer sera compared to normal sera (p<0.05), in addition to a declining expression with the advanced pTNM stage from stage I to IV of gastric cancer patients. Area under the receiver operating characteristic (ROC) curve was 0.78 for the expression of CFI precursor (p<0.01). CONCLUSIONS: 2-DE-based serum proteome analysis may be useful in the screening of serum biomarkers for gastric cancer. CFI precursor could aid in the diagnosis and indicate the advancement of gastric cancer.

Adult↗
PubMed1999

Protective T cell-independent antiviral antibody responses are dependent on complement.

Complement is part of the innate immune system and one of the first lines of host defense against infections. Its importance was evaluated in this study in virus infections in mice deficient either in soluble complement factors (C3(-/-), C4(-/-)) or in the complement signaling complex (complement receptor [CR]2(-/-), CD19(-/-)). The induction of the initial T cell-independent neutralizing immunoglobulin (Ig)M antibody response to vesicular stomatitis virus (VSV), poliomyelitis virus, and recombinant vaccinia virus depended on efficient antigen trapping by CR3 and -4-expressing macrophages of the splenic marginal zone. Neutralizing IgM and IgG antibody responses were largely independent of CR2-mediated stimulation of B cells when mice were infected with live virus. In contrast, immunizations with nonreplicating antigens revealed an important role of B cell stimulation via CR2 in the switch to IgG. The complement cascade was activated after infection with VSV via the classical pathway, and active complement cleavage products augmented the effector function of neutralizing IgM and IgG antibodies to VSV by a factor of 10-100. Absence of the early neutralizing antibody responses, together with the reduced efficiency of neutralizing IgM in C3(-/-) mice, led to a drastically enhanced susceptibility to disease after infection with VSV.

Animals↗
PubMed2003

Viraemia, cryoglobulins and autoantibodies in haemodialysis patients infected with hepatitis C virus.

OBJECTIVES: The clinical features of hepatitis C virus (HCV) infection depend on the immune and autoimmune reactions induced by the virus. Chronic renal failure might alter the pattern of these reactions. The aim of this study was to determine the prevalence of cryoglobulinaemia, the frequency of autoantibodies and HCV viral load in HCV infected Greek patients on chronic haemodialysis. METHODS: Seventy-three HCV Ab(+) patients on maintenance haemodialysis and 87 otherwise normal patients with chronic HCV infection were evaluated for the presence of cryoglobulins, autoantibodies and viral markers. RESULTS: Cryoglobulins were detected in 22/73 (30.1%) haemodialysis patients and in 23/87 (26.4%) patients with normal renal function (NS). The mean cryocrit value was significantly lower in the haemodialysis group ( = 0.002). Haemodialysis patients had significantly higher levels of C4 component of complement and lower incidence of rheumatoid factor than those of patients with normal renal function. Serum HCV RNA levels were found significantly lower in the haemodialysis group (median, 2.20 Meq/ml; range, 119.9 Meq/ml) than in the group with normal renal function (median, 4.50 Meq/ml; range, 114.9 Meq/ml; = 0.046). The distribution of genotypes was not different between the two groups. CONCLUSIONS: There are subtle differences in autoimmune features of HCV infection if the patients are also haemodialysed for renal failure. HCV viral load is lower in haemodialysis patients, with no difference in the HCV genotype prevalence. The clinical significance of these findings is unknown.

Adult↗
PubMed1978

Levels of complement components during allergen-induced asthma.

The levels of circulating complement components C3 and C4, total haemolytic complement, CH50, as well as evidence of complement activation, have been studied in peripheral blood samples during allergen-induced asthma. No evidence of activation of the complement system was detected in these studies.

Allergens↗
PubMed1978

Some observations on the immunological status in scleroderma (progressive systemic sclerosis).

A variety of tests were performed to determine the immune status of a group of patients with scleroderma (progressive systemic sclerosis). Sera of 11 of 35 patients showed autoantibodies by an immunofluorescent technique. There was no significant difference between the C3 and C4 components of complement in 12 patients tested and laboratory controls. IgM levels were raised in 24 of 34 sera. Four of ten patients showed some deficiency of phagocytic function in the leucocyte iodination test. B cell and T cell numbers were normal in the eight patients tested. Reactivity to mitogens was usually normal in ten patients tested with a deficient response to one of the three mitogens in two patients. In skin reactivity tests in 23 patients, only one was anergic to all of the four antigens tested. It is concluded that although some immune abnormalities are common in scleroderma there is no consistent abnormality in any of the tests used. This does not exclude the possibility that immune factors may be involved in systemic manifestations of the disease, or that there may be some subtle specific abnormality not revealed by the tests performed.

Adult↗
PubMed2005

Pregnancy outcome in recurrent aborters is not influenced by Chlamydia IgA and/or G.

PROBLEM: It is unclear whether chlamydia infection influences the miscarriage rate and immunological factors in patients with recurrent miscarriage. METHOD OF STUDY: Chlamydia DNA, IgA and IgG to Chlamydia trachomatis, natural killer cell activity, complement 3 (C3), C4, hemolytic complement, antinuclear antibodies, antiphospholipid antibodies, prolactin, activated partial thromboplastin time, prothrombin time and fibrinogen were examined in 504 patients with a history of two or more consecutive first-trimester miscarriages. Subsequent pregnancy outcomes were compared between cases with and without antibodies to C. trachomatis. RESULTS: Totals of 10 of 30 and 48 of 201 patients receiving no medication miscarried subsequently with and without chlamydia infection. Chlamydia IgA and/or IgG were associated with a high level of C3 but not other immunological and coagulatory parameters. CONCLUSION: Antibodies to C. trachomatis do not influence subsequent pregnancy outcome in patients with a history of recurrent miscarriage.

Abortion, Habitual↗
PubMed2006

Immunological profiles of patients with chronic myeloid leukaemia. I. State before the start of treatment.

In view of the increasing interest in the immunotherapy of CML it seems highly desirable to broaden the present knowledge on the immune reactivity of CML patients. A group of 24 patients and 24 healthy controls were studied for the total of 15 immunological parameters, including the prevalence of antibodies against human herpesviruses and papillomaviruses. To clearly discriminate between changes associated with the disease and those induced by the therapy, all patients were enrolled prior to the start of any anti-leukaemic therapy. Statistically significant differences between patients and controls were found in the levels of IgA, C4 component of complement, CRP and IL-6, the production of Th1 cytokines in stimulated CD3 cells and the E. coli stimulatory index. The analysis of the interrelationship between the results obtained in the individual patients presented some unexpected findings, such as the lack of correlation between the CRP and IL-6 levels. It will be the purpose of a follow-up to determine whether and how the immune status of the patients prior to the treatment correlates with their response to therapy and how the individual immunological profiles change in the course of the disease. These observations will be utilized in the future immunotherapeutic studies to constitute the vaccine- and placebo-treated groups.

Adult↗
PubMed2000

[C4 deficiency].

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Complement C4↗