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Immune status and autoantibody formation in children with chronic hepatitis B infection.

BACKGROUND: The hepatitis B virus (HBV) causes a wide spectrum of disease which ranges from acute hepatitis to liver cirrhosis. Patients who fail to mount a vigorous immune response in acute HBV develop chronic infection. Therefore, the aim of the study was to determine the cellular and humoral immune parameters of the patients with chronic HBV and to evaluate the prevalence of autoantibodies before the beginning of immunomodulator and antiviral therapy. METHODS: In this comparative study, serum immunoglobulins, IgG subclasses, secretory IgA, serum complement components, lymphocyte subsets and CD11a, CD18, CD54 molecules on lymphocytes were determined in 44 hospitalized patients of chronic HBV infection and 20 cases of healthy control subjects. RESULTS: Significant increase in IgG and significant decrease in the complement C4 were observed. The mean percentage of CD3+ lymphocytes, reflecting the percentage of total T cells was significantly higher in the patient group due to the increase of CD8+ lymphocytes. The mean percentage of CD19+ B lymphocytes was lower in the patient group secondary to the increase of their total T cells. No significant difference was found in cell surface adhesion molecules between patient and control groups. The percentage of antinuclear antibody positivity was 18.2%. CONCLUSIONS: Our data show that ANA formation is part of the natural course of chronic HBV infection and this value may reflect the tendency to autoimmune diseases and the importance of clinical follow-up. The abnormalities observed in immunological parameters may reflect the role of the cellular and humoral immune system in pathogenesis.

Adolescent↗

[The correlation between anticardiolipin antibodies and disease activity in patients with systemic lupus erythematosus].

This study was conducted to determine the prevalence and clinical association of anticardiolipin antibodies (ACA) in serum of patients with systemic lupus erythematosus (SLE). ACA (IgG, IgA, IgM) was measured by enzyme-linked immunosorbent assay (ELISA) in the serum sample of 87 patients of SLE. The prevalence rates of ACAIgG, ACAIgA and ACAIgM were 62.1%, 52.9% and 35.6% respectively. The titers of ACAIgG and ACAIgM were positively correlated with the disease activity (r = 0.2763, P = 0.044; r = 0.3294, P = 0.018); ACAIgG, ACAIgA and ACAIgM were negatively correlated with complement C3 (r = -0.4737, P = 0.000; r = -0.2990, P = 0.017; r = -0.2758, P = 0.029); and ACAIgG was negatively correlated with complement C4 (r = -0.4079, P = 0.005). The titers of ACAIgA in patients with thrombosis was higher than that in patients without thrombosis. The patients with central nervous system involvement (CNS-SLE) had significantly higher ACAIgG and ACAIgM titers, compared with those without CNS-SLE. The results indicate there is a correlation between ACA titers and disease activity. In patients with thrombosis, the titer of ACAIgA is higher, and in patients with CNS-SLE, the titers of ACAIgG and ACAIgM are higher.

Adolescent↗

A case of severe C4d-positive kidney allograft dysfunction in the absence of histomorphologic features of rejection.

Acute antibody-mediated (humoral) renal allograft rejection has emerged as a clinicopathological entity that carries a poor prognosis. Its diagnosis is based on typical pathohistologic features, serologic detection of donor-specific alloantibodies and the immunohistochemical finding of endothelial deposits of the complement split product C4d. We herein report a case of severe antibody-mediated graft injury after spousal-donor kidney transplantation. Despite an increased risk for humoral presensitization in the female recipient (three previous pregnancies), donor-specific alloantibodies were not detectable before transplantation. After initial graft function, severe graft dysfunction occurred one week after transplantation. A renal biopsy revealed no histomorphologic features of rejection. However, immunohistochemical detection of diffuse C4d deposits along peritubular capillaries suggested acute humoral rejection. The diagnosis of antibody-mediated rejection was confirmed by the detection of de-novo production of anti-donor alloantibodies. Graft dysfunction was resistant to high dose steroids or antilymphocyte antibody therapy. However, a recovery of graft function could be achieved by antibody elimination using immunoadsorption therapy. This case reinforces the high diagnostic value of C4d staining. In severe graft dysfunction humoral immune mechanisms should be considered, even when histopathologic features of humoral rejection are completely absent.

Adult↗

[Angioneurotic hereditary edema. 3 faimilial cases].

The study involved three families with hane. This disorder differs from the simple condition by its preferential visceral localisation (digestive and, above all, the glottis), its hereditary nature and the existence of a biological abnormality affecting the serum complement system (absence of enzyme activity of C1 esterase inhibitor in the serum of sufferers). The cases reported illustrate the serious prognosis of this condition (four deaths by asphyxia in one family) in the absence of specific therapy. This disorder, although rare, represents a fundamental problem in general pathology by virtue of the enzymatic, immunological and genetic processes which it involves.

Adolescent↗

[Concentration of serum proteins in children with down syndrome].

In the serum of 41 children with trisomy 21 (Down syndrome) the concentration was determined of 10 proteins by the radial immunodiffusion method. It was found that the concentration of prealbumin and alpha 2-macroglobulin was lower than in healthy children. The concentration of acid alpha 1-glycoprotein, alpha 1-antitrypsin, haptoglobin, C4 complement component, and hemopexin was higher than in healthy children. The concentration of ceruloplasmin, C3 complement component, and transferrin was similar as in healthy children.

Blood Proteins↗

Activation of the alternative pathway by pneumococcal cell walls.

The present studies were performed in order to identify the pneumococcal subcellular component responsible for activating the alternative pathway. Purified pneumococcal cell walls were able to activate the alternative pathway at a concentration as low as 5 mug/ml and were more active than crude cell walls, which in turn were more active than the whole organism. Purified pneumococcal cell membranes also were able to activiate the alternative pathway but had less than 10% of the activity of the purified walls. Thus, the cell wall appears to play a major role in pneumococcal activation of the alternative pathway. Pneumococcal cell walls containing ethanolamine were as effective as cell walls containing choline in activating the alternative pathway. Since C-reactive protein binds specifically to the phosphorylcholine residue of pneumococcal C-polysaccharide, it is unlikely that pneumococcal cell walls must combine with C-reactive protein in order to activate the alternative pathway.

Animals↗

[Use of pulsed steroid therapy in active rheumatoid arthritis].

The authors implemented a prospective double blind, controlled study where they administered to a group of 34 patients with active rheumatoid arthritis either three pulses a 1000 mg methyl prednisolone in a small infusion or an infusion with placebo. They proved a very favourable effect--after five days a marked diminution of morning stiffness was recorded, as well as a diminution of pain during locomotion and rest and general improvement of the patient's condition. After two weeks the effect declines but even after 8 weeks the difference, as compared with the initial value, was still significant, while this was not the case after placebo. The sedimentation rate increased after the initial decline to the baseline level. A number of immunological indicators (decline of immunoglobulins, IgG rheumatoid factor, rise of C3 and C4 complement levels and rise of T lymphocytes) suggest an anti-inflammatory and immunosuppressive action persisting for several weeks although the mentioned results were not statistically significant (the majority at the very borderline of significance, probably significant in a larger number of patients). The authors confirm the reactive safety of this treatment, emphasize the necessity to investigate contraindications of treatment (diabetes mellitus) and the necessity to follow up patients in inpatient facilities.

Arthritis, Rheumatoid↗

Plasma histamine but not anaphylatoxin levels correlate with generalized urticaria from infusions of anti-lymphocyte monoclonal antibodies.

Anti-lymphocyte monoclonal antibodies have shown promise in trials for therapy of lymphocyte malignancies but are associated with a high frequency of immediate-type anaphylactoid reactions. We have previously demonstrated that these immediate-type anaphylactoid reactions are not mediated by immunoglobulin E to anti-lymphocyte monoclonal antibodies. To gain insight into the mechanisms of these immediate-type anaphylactoid reactions, we measured plasma levels of histamine and anaphylatoxins (C3a, C4a, C5a) during 11 infusions in eight patients who received anti-lymphocyte monoclonal antibodies (T101 and Lym-1). Three patients experienced generalized urticaria (two with severe angioedema); a fourth patient had three isolated hives but without generalized manifestations of an immediate-type anaphylactoid reaction. Plasma histamine levels after infusions that were associated with generalized urticaria were significantly higher than those during infusions that were not associated with generalized urticaria (mean, 3.47 vs 0.18 ng/ml, p less than 0.001). Increases in C3a and C4a levels were observed after some infusions, but these did not correlate with generalized urticaria. Measurable rises in plasma C5a levels after infusions were not detected. Although these data should be viewed as preliminary considering the limited number of patients studied, the observed histamine release demonstrates that mast cell or basophil activation that is not mediated by immunoglobulin E to anti-lymphocyte monoclonal antibodies occurs in the pathogenesis of immediate-type anaphylactoid reactions from anti-lymphocyte monoclonal antibodies. Although activation of the classical complement pathway may occur in some anti-lymphocyte monoclonal antibody infusions, this does not appear to explain immediate-type anaphylactoid reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylatoxins↗

Hereditary and acquired angioedema: experience with patients in Puerto Rico.

Hereditary (HAE) and acquired (AAE) angioedema are vascular reactions involving the sub mucosal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries. HAE and AAE are clinical disorders characterized by angioedema that require prompt differentiation from other causes of angioedema in order to receive the most pertinent and effective therapeutic interventions. The aim of this report is to describe the clinical characteristics of patients with both HAE and AAE identified and followed at the Immunology Clinic of the University Hospital at the Puerto Rico Medical Center, their response and side effects to danazol therapy and their comparison with other series of similar patients reported in the literature. Overall, the patients in this sample presented a similar clinical profile compared to other reported series in the literature.

Adolescent↗

Cryoglobulinemia vasculitis following intravesical instillations of bacillus Calmette-Guerin.

Infections and/or immune-mediated reactions may occur after intravesical instillation of bacillus Calmette-Guérin for the treatment of bladder carcinoma. We report herein a cryoglobulinemia vasculitis occurring after intravesical BCG instillation for a superficial papillary transitional cell bladder carcinoma. The patient, an 80-year-old man, presented peripheral ischemia 10 days after the second course of intravesical BCG instillation. Biological evaluation revealed autoimmune thrombocytopenia, hypergammaglobulinemia, low C3 and C4 complement fraction levels related to mixed cryoglobulinemia and lupus anticoagulant. The patient was treated with heparin and prostacyclins with a good outcome. All of the immune anomalies spontaneously regressed within 3 months. To our knowledge, cryoglobulinemia has only been reported once in the literature and lupus anti-coagulant has never been reported as a complication of intravesical BCG instillation.

Adenocarcinoma↗

Induction of C3 expression in astrocytes is regulated by cytokines and Newcastle disease virus.

Synthesis of complement proteins and their regulation in resident cells of the central nervous system are important pathophysiologic factors that can affect the outcome of inflammatory central nervous system diseases. Primary cultures of rat astrocytes constitutively express C3 mRNA and produce C3 protein; both of them were enhanced by LPS or by a live as well as inactivated Newcastle disease virus, a neurotropic paramixovirus. TNF, IL-1 beta, and IL-8 also increased the levels of C3 mRNA and protein whereas IL-1 alpha and IL-6 had no effect, although all of these cytokines are inducible by LPS. LPS stimulation in the presence of cycloheximide decreased the LPS-mediated C3 mRNA induction by 60%. These data suggest that LPS effect on C3 regulation is mediated directly by LPS as well as by LPS-induced cytokines. Interestingly, C3 mRNA induced by Newcastle disease virus or inactivated Newcastle disease virus was inhibited by protein kinase inhibitors, H-7 and staurosporine, whereas these inhibitors had no effect on C3 induction mediated by LPS or cytokines, indicating the existence of different signal transduction pathways.

Alkaloids↗

[Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes].

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.

Adult↗