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Use of a variety of biological parameters in distinguishing cirrhotic from malignant ascites.

Twenty-two different protein measurements were taken in the serum and ascitic fluid of fifty consecutive patients in an attempt to investigate which tests are the most reliable for the differential diagnosis of ascites. Serum and ascitic fluid total proteins (TPR), albumin (ALB), lactate (LAC), ferritin (FER), C3 and C4 complement factors, C-reactive protein (CRP), ceruloplasmin (CER), alpha2-macroglobulin (alpha2MG), haptoglobin (HAP), alpha1-antitrypsin (alpha1AT), alpha1-acid glycoprotein (alpha1AG), transferrin (TRF), immunoglobulins IgG, IgA, IgM and cytokines such as interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were measured to distinguish between malignant and cirrhotic ascites. Correlations and non-parametric Mann-Whitney tests were used for ascitic fluid:serum ratio comparisons between the two groups. Multivariate analyses were used to determine the most significant biochemical ratio predictors for the differential diagnosis and a recursive partitioning model was constructed. Highly positive correlations (r>0.50) were found between the ratios IgA, IgG, IgM, CER, alpha2 MG, HAP, alpha1AT, alpha1AG and TRF. There was evidence that TPR, ALB, LAC, FER, IgG, CER, alpha2MG, alpha1AT, alpha1AG, TRF and IL-8 ascitic fluid:serum ratios are significnatly higher in patients with malignant neoplasms than in cirrhotics. In the recursive partitioning model the most significant parameters were found to be the ratios of albumin and IL-1alpha. The model fitted allowed for 100% correct classification of ascites. In conclusion, we have shown that a simple and very accurate model based on two ascitic fluid: serum measurements is able to differentiate between malignant and non-malignant ascites.

Acute-Phase Proteins↗

Action of nonviral gene delivery vectors on human complement system: low anticomplementary activity of lipoplexes based on lacZ plasmid and phospholipid/oligocation liposomes.

A simple test-system has been developed for the first time in order to detect the ability of effectors (lipoplexes) to activate the complement system in an antibody-independent manner to serve as acceptors of nascent C4b and to inhibit formation of the key enzyme of complement, C3-convertase. The effect of plasmid DNA (pCMV-SPORT-LacZ), negatively charged cardiolipin (CL), neutral phosphatidylcholine (PC) vesicles and their lipoplexes, on the complement system was studied using the method developed. It was revealed that PC vesicles did not affect the complement system, while CL vesicles manifested low activation. The influence of plasmid DNA and its lipoplex based on PC liposomes as well on the complement system was very low. PC/LacZ lipoplex (143 microg/ml) acted on the complement system like 5.36 microg/ml heat aggregated IgG (agg) (the level of no pathological ruptures), whereas CL/LacZ lipoplex (143 microg/ml) acted similar to 10.7 microg/ml IgG (agg). Thus, weak activation of the complement system with CL lipoplex, and even weaker for the PC lipoplex testified to the use of neutral and positively charged lipoplexes preferably in gene therapy protocols. The technique can also be used for testing the influence of injectable gene therapy vectors on the complement system.

Animals↗

[Critical considerations on the behavior of immunoglobulins in rheumatoid arthritis].

Critical evaluation of immunoglobulins in Rheumatoid Arthritis. It has been studied the behavior of the serum and synovial immunoglobulins of 62 patients afftected arthritis reheumatoid in various clinic stages; the valued have been expressed in mg% and mg/g of proteins. The serum levels of the IgG and IgA are higher in the cases of R.A. than in normals. The synovial concentrations of the IgA and IgM are lower than the respective serum values, while the phenomenon is less evident for the IgG probably because the last are synthetised in the synovial means. It exists, however, a interdipendence between the concentration of the serum and synovial immunoglobulins. The concentrations of the immunoglobulines, both serum and synovial, are not in relation with the most usual humoral phlogosis-tests, as well as they are not correlable with the values of the naturals antiproteases and with some fractions of the complement (both of the classic and alternative pathway). The variations of the immunoglobulins are, in the R.A., aspecific and of different intensity therefore their determination is not proposable neither as test of measure of the phlogosis nor as index of disease.

Adult↗

Complement activation by a univalent hapten-antibody complex.

The univalent hapten, nonadeca lysyl epsilon-Dnp-lysine, binds tightly to rabbit anti-2,4-dinitrophenyl antibody, and the complex has a sedimentation coefficient of 6.7, characteristic of a single antibody molecule. In this communication, we show that this complex is a good activator of the serum complement system. For activation to occur, the univalent hapten must contain the specific group which binds to the antibody, and also the polycationic chain. In addition, activation requires a functional complement-binding region on the intact antibody molecule. The classical pathway appears to be involved since the first, fourth, and second components of complement are markedly depleted when the complement system is activated by this univalent hapten-antibody complex.

Animals↗

[Systemic manifestations of idiopathic inflammatory myopathies--part one].

Dermatomyositis and polymyositis are the idiopathic inflammatory myopathies of autoimmune origin. Apart from muscle weakness, general symptoms such as the affection of visceral organs and altered indicators of humeral immunity occur in a minority of patients. The aim of the study was to establish whether the systemic manifestations of the disease, altered immunoserologic parameters and findings of muscle vasculitis occurred more frequently in patients with dermatomyositis or polymyositis. The frequency of clinic, serologic and histopathologic alterations in the groups of patients with dermatomyositis and polymyositis was determined. In order to determine the degree and importance of the frequency, the following parameters were calculated: the relative rations of frequencies and the importance of the difference in frequencies of particular alterations between the groups of patients. It was found that extramuscular manifestations of the disease such as arthritis, pulmonary, cardiac and renal changes, the increased activity of C3 and C4 complement components as well as vasculitis of muscle and skin tissue occurred more frequently in patients with dermatomyositis. This finding indicates that patients with DM, regardless of the degree of muscular affection, may have a more severe clinical course of the disease and a poor prognosis.

Adult↗

Progress in understanding humoral rejection in kidney transplantation: implications for patient management.

After more than 40 years of clinical renal transplantation, the contribution of humoral immunity to the pathogenesis of allograft rejection is progressively being clarified. With the advent of a new generation of immunosuppressive agents, the production and consequences of anti-donor alloantibodies can now be controlled. In the upcoming years, immunosuppressive regimens that will specifically control both T- and B-cell responses may further improve long-term allograft survival, if the immunosuppressive efficacy of such regimens is not hampered by an increase in infectious, neoplastic or cardio-vascular complications.

ABO Blood-Group System↗

Complement activation in seropositive and seronegative rheumatoid arthritis. 125I-C1q binding capacity and complement breakdown products in serum and synovial fluid.

1. The detection and quantitation of immune complex-like material in synovial fluid and in serum from patients with joint diseases was done through the measurement of the capacity to bind radiolabeled C1q. It was found that 65% of synovial fluid samples from seropositive or seronegative RA patients had a high C1q binding capacity as compared to other joint diseases. Immune complex-like material was also detected in 63% of serum samples from seropositive RA patients. 2. The existence of C3 or C3PA breakdown products in synovial fluid from most of the synovial fluids from RA patients probably reflects an activation of the complement system occurring in both forms of the disease. C3PA breakdown products were never found in degenerative or post-traumatic joint diseases and only occasionally in other inflammatory arthritis. Apart from their pathogenic significance, these results may have some interest for the clinical investigation of patients with joint diseases.

Arthritis, Rheumatoid↗

Activation of the classical and alternate pathways of complement by Corynebacterium parvum.

The immunological adjuvant Corynebacterium parvum has been to activate the alternate pathway of complement in human and guinea-pig serum. Human serum in addition contains anti-C. parvum antibodies leading to activation of the classical complement pathway. The possible role of a C. parvum derived polysaccharide in this activation is considered in relation to the biological effects of the micro-organism.

Agglutination Tests↗

The influence of selenium supplementation on the immunity of corticoid-dependent asthmatics.

UNLABELLED: Selenium (Se) is a trace element that is essential for immune functions, and protects the immune system from oxidative damage. AIM: The aim of the pilot clinical study was to assess the influence of selenium supplementation (SeS) on the selected immune parameters analyzed from peripheral blood of corticoid-dependent asthmatics (CDAs). MATERIAL AND METHODS: Seventeen CDAs aged from 30 to 74 years (7 females, 10 males) with suboptimal levels of Se in plasma were enrolled into the study. The follow up of SeS lasted 96 weeks. It is daily dose was 200 micrograms (2 x 2 tbl daily, 1 tbl contained 50 micrograms of Se). Before (-4 weeks) and after the 12th, 48th, 72nd and 96th weeks of SeS, the following parameters were observed: Epitopes EG1, EG2 expressed on intracellular eosinophil (Eo) cationic protein and eosinophil peroxidase, the numbers of CD3, CD4, CD8, CD19 and CD3 HLADR positive T lymphocytes (Ly), lymphocyte blastogenesis test (LTT) with mitogens concanavalin A, (Conc A) phytohemaglutin (PHA), the levels of C3, C4 complement components, activation of complement by classic and alternative pathways (CP50, AP50), the levels of immunoglobulins (Ig) G, A, M and total IgE, circulating immune complexes (CIC). RESULTS: Epitopes EG1 and EG2 in cytoplasma of Eo decreased significantly after 12 weeks of SeS, (p < 0.01) and 96 weeks of follow up. In parameters of T cell mediated immunity the relative number of CD3 HLADR+ T Ly increased after 24, 48 and 96 weeks of SeS (p < 0.0008, p < 0.009, p < 0.07). Proliferative activity of T Ly to mitogenes PHA and ConcA in LTT decreased significantly after 12, 48, 72 and 96 weeks of SeS (p < 0.0005, p < 0.009, p < 0.04, p < 0.02, respectively). In humoral parameters activation of CP50 decreased after 24, 72 and 96 weeks of SeS to the reference range (p < 0.001, p < 0.03, p < 0.02) and AP50 after 96 weeks, respectively (p < 0.02). The levels of IgG elevated after 24 weeks (p < 0.02), IgA after 24, 48 weeks (p < 0.0007, p < 0.02, respectively). The level of total IgE significantly decreased after 96 weeks of SeS (p < 0.003). CONCLUSION: Our pilot clinical study with the CDAs demonstrates the significant changes particularly in functional parameters of both cellular and humoral types of immunity. These results support the immunomodulating effects of SeS. (Tab. 5, Ref. 15.)

Adult↗

Complement's participation in acquired immunity.

The preliminary evidence for the involvement of complement in promoting primary humoral responses dates back over a quarter of a century. However, it is only in the course of the past decade or so that the detailed mechanisms underlying complement's influence have been characterized in depth. It is now clear that complement serves as a regulator of several B cell functions, including specific antibody production, antigen uptake, processing and presentation, and shaping of the B cell repertoire. Of key importance, in this respect, is the role played by the B cell-signaling triad consisting of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses.

Animals↗

[The activation of the complement system in various connective tissue diseases].

A knowledge of the complement system in patients with collagen diseases is of interest as it may serve to indicate the existence of activity or non-activity in these diseases. We have studied the existence or non-existence of the activity of the complement system through evaluation of the levels of C3, as well as the implicated mechanism of the classical or alternate pathways through the measure of C'4 and C'3 proactivator components. Quantitation of complement components was obtained by electroimmunodiffusion, employing specific antiserum. From the results obtained, we observed that the complement activity in patients with SLE, the classic pathway was affected more (7 patients of the 24 studied), than the alternate pathway (3 patients). However, in those patients affected by sclerodermia, there seems to be an equal incidence of the activation of complement through both pathways (2 patients with activation through each way). Also of interest is the existence of a patient with SLE and another affected by sclerodermia in which a selective reduction of C'3 was observed. This observation suggests the possible existence of a selective destruction, perhaps mediated through a factor type such as the nephritic factor. However, there may exist other patients of whom we have already commented on, with a parallel reduction in the three components which suggests a change in the synthesis or in the simultaneous activation in both of the pathways. When realizing the comparative studies of the state in which the immunoglobulins (IgG, IgA and IgM) and complement components are to be found, the conclusion is that there is no significative correlation between the two. This is particularly interesting as it assumes the necessity of knowing the state of the complement and not only of the immunoglobulin, in order to know the state of activity in which the process is.

Complement C3↗