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Circulating immune complexes in tuberculosis.

Using a polyethylene glycol precipitation method, immune complexes were detected in 56% of patients with active tuberculosis. After antituberculous treatment, 29% remained positive for immune complexes, a frequency similar to that in a group of racially matched clinic controls (35%). In a study of 17 patients whose immune complex levels were determined soon after diagnosis and again when the therapy had ceased, there was a significant decrease in complexed IgM and Clq. Sequential studies of immune complex levels in tuberculosis merit further investigation, their persistence may indicate the continued presence of antigens, and their disappearance from the circulation may be a guide to successful treatment.

Adolescent↗

A baboon syndrome induced by intravenous human immunoglobulins: report of a case and immunological analysis.

Following the second series of intravenous human immunoglobulins (IVIg; 0.4 g/kg) prescribed to treat a sensorimotor polyneuritis, a 28-year-old woman developed pompholyx that recurred after each of the following monthly treatments with IVIg. During the administration of the 10th series, the patient developed a typical baboon syndrome. Immunohistochemical studies of a skin biopsy revealed an unexpected epidermal expression of P-selectin, usually expressed by endothelial cells. Patch, prick and intradermal tests performed with IVIg on the back, arms and buttocks gave negative results on immediate and delayed readings. IVIg were re-administered, with the informed consent of the patient, and induced a generalized maculopapular rash. This is the first reported case of baboon syndrome induced by IVIg. Although extensive skin testing was performed, all test sites remained negative. We wonder whether IVIg could reproduce immunological mechanisms involved in the 3 types of systemic contact dermatitis (pompholyx, baboon syndrome and maculopapular rash), including the epidermal expression of P-selectin.

Adult↗

Circulating immune complexes after cadaver kidney transplantation.

351 sera from 27 human recipients of renal allografts and 21 healthy blood donors were assayed for circulating immune complexes by the Clq solid-phase radioimmune assay. Increased Clq-binding activity (Clq-BA) was detected in pretransplant sera from 5 patients with chronic pyelonephritis (PN) and 3 patients with chronic glomerulonephritis (GN). A significant decrease of Clq-BA immediately after transplantation could not be found. 6 weeks after transplantation only 2 patients of the PN group showed increased Clq-BA. Serial studies in 17 patients with rejection crises did not show any correlation between the level of serum Clq-BA and the occurrence of rejections. Furthermore, no correlation could be found between the occurrence of complement-dependent lymphocytotoxic antibodies measured by the 51Cr release technique and the level of serum Clq-BA. In contrast, our results show that the probability of graftectomy or graft failure is significantly higher, at least in the early phase after transplantation, when the serum Clq-BA is lowered for several weeks.

Antibodies↗

Cryoglobulinemia and fibronectin.

Isolated and washed cryoglobulins obtained from 30 patients with different diseases were studied for the presence of fibronectin by immunoelectrophoresis. Two of the isolated cryoglobulins were of the type I, 3 were of the type II, while the other 25 were of type III. Despite extensive washing, fibronectin was detected in all the cryoprecipitates. Our results indicate the constant presence of fibronectin in the cryoprecipitates from patients with different diseases and types of cryoglobulin. The possible mechanisms by which fibronectin could act in the precipitation of immunoglobulins are discussed.

Complement Activating Enzymes↗

Immune complexes of IgG1 and IgG3 subclasses in human breast cancer sera detected by monoclonal antibodies in an indirect immunoenzymatic assay.

Circulating immune complexes (CIC) of the IgG class were detected in sera from 37 (35.58%) out of 104 of the preoperated breast cancer patients studied using a CIq solid-phase enzymatic assay. Sera of positive patients were then tested to identify the IgG subclasses which are part of the complexes with the aim of showing a better correlation between CIC and disease evolution. IgG1- and IgG3-CIC were indirectly detected by the above test using monoclonal antibodies against the mentioned subclasses. Curves obtained with aggregated IgG1 and/or IgG3 showed good sensitivity and specificity of the test. Complexes containing both IgG1 and IgG3 were present in sera from the majority of patients; however, the relative amounts of these subclasses varied from patient to patient.

Antibodies, Monoclonal↗

Association of anti-F (ab')2 antibodies (pepsin agglutinators) with immune complexes as determined by enzyme-linked immunosorbent assays.

A solid-phase assay for the detection of anti-F(ab')2 antibodies is described. Wells of microtiter plates are coated with F(ab')2, dilutions of sera are added, and IgG bound to the solid phase is detected using peroxidase-labeled Protein A. Anti-F(ab')2 antibodies were found in 61% of sera from patients with rheumatoid arthritis, 77% with subacute bacterial endocarditis , and 34% with systemic lupus erythematosus. Simultaneous analysis of these sera for immune complexes (IC), using modified Clq and monoclonal rheumatoid factor assays, showed that a correlation existed between anti-F(ab')2 antibodies and the levels of IC. Characterization of anti-F(ab')2 antibodies by inhibition and absorption experiments and by immunological and physical means indicated that they were similar to serum proteins described in the 1960s and designated pepsin agglutinators.

Antibodies, Anti-Idiotypic↗

Early rheumatoid-like synovial lesions in rabbits drinking cow's milk. II. Antibody responses to bovine serum proteins.

Thirty-six percent of Old English rabbits fed pasteurized cow's milk developed early rheumatoid-like synovial lesions. All rabbits drinking milk developed high titres of serum and synovial fluid Clq-binding activity. This has been shown to be due to specific antibody to Clq, produced in response to Clq in cow's milk. In addition, these rabbits responded to other bovine proteins present in cow's milk, including conglutinin, beta-lactoglobulin and IgG. There was no correlation between serum or synovial fluid titres of antibody to bovine milk proteins and synovial lesions.

Animals↗

Comparison of the arthritogenic properties of dietary cow's milk, egg albumin and soya milk in experimental animals.

The arthritogenic effect of dietary cow's milk, egg albumin and soya milk were compared in Old English rabbits. The 12-week cow's milk feeding regimen produced the highest incidence of significant joint lesions. Lesions were evident but mild at 5 weeks and the synovitis had resolved by 32 weeks. It is suggested that the transient nature of the synovitis may be due to the development of specific secretory IgA antibodies which were detectable in faecal pellet extracts. Sandy Lop rabbits were less susceptible to the arthritogenic effect than were Old English rabbits. Dietary ovalbumin was less arthritogenic than cow's milk despite high titres of serum and synovial fluid antibodies and immune complexes. The rabbits were 'tolerant' to dietary soya due probably to pre-existing levels of soya protein in their diet. Lewis and Wistar strain rats, CBA, Balb/c and C57/BL6 mice fed on cow's milk for 3 months did not develop serum antibodies or synovial lesions. It is suggested that this allergic synovitis is not a model for early rheumatoid joint disease because of the transience of the lesions and lack of stimulation of rheumatoid factor. It may well, however, be a model for the arthralgia seen in patients with certain food allergies.

Animals↗

Secondary erythermalgia associated with an autoimmune disorder of undetermined significance.

A 50-year-old female patient is described with an acquired, persisting and yet incurable erythermalgia featured by symmetric burning pain and red congestion of the extremities secondary to cutaneous vasculitis. A weakly positive antinuclear antibody titer and high titers of antibodies against gastric parietal mucosa cells pointed to an underlying but unclassifiable autoimmune disorder. It is concluded that histopathology of lesional skin contributes to the differential diagnosis of primary and secondary erythermalgia.

Antibodies, Antinuclear↗

Antigenic similarities within circulating immune complexes in patients suffering from cutaneous vasculitis.

Circulating immune complexes (IC) were searched by 2% polyethylene glycol precipitation in 24 patients with clear-cut clinical cutaneous vasculitis. 13 patients were IC-positive. Isolated IC were shown to cross-react specifically within three different groups. One group possessed the same or highly similar antigenic determinants in circulating IC. No correlation was found between common antigenic determinants in IC and the histological and clinical features of the disease.

Antigen-Antibody Complex↗

Surfactant protein A differentially regulates IFN-gamma- and LPS-induced nitrite production by rat alveolar macrophages.

Although several studies have demonstrated that the pulmonary collectins surfactant protein (SP)-A and SP-D contribute to innate immunity by enhancing pathogen phagocytosis, the role of SP-A and SP-D in regulating production of free radicals and cytokines is controversial. We hypothesized that the state and mechanism of activation of the immune cell influence its response to SP-A. The effects of SP-A and SP-D on production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were assessed in isolated rat alveolar macrophages activated with lipopolysaccharide (LPS), interferon gamma (IFN-gamma), or both agonists. SP-A inhibited production of NO and iNOS in macrophages stimulated with smooth LPS, which did not significantly bind SP-A, or rough LPS, which avidly bound SP-A. In contrast, SP-A enhanced production of NO and iNOS in cells stimulated with IFN-gamma or INF-gamma plus LPS. Neither SP-A nor SP-D affected baseline NO production, and SP-D did not significantly affect production of NO in cells stimulated with either LPS or IFN-gamma. These results suggest that SP-A contributes to the lung inflammatory response by exerting differential effects on the responses of immune cells, depending on their state and mechanism of activation.

Animals↗

Network theory in autoimmunity. In vitro suppression of serum anti-DNA antibody binding to DNA by anti-idiotypic antibody in systemic lupus erythematosus.

Regulation of serum anti-DNA antibody in systemic lupus erythematosus (SLE) by an antiidiotypic antibody was evaluated. Various sera from SLE patients in active and inactive states of their disease, as well as sera from normal individuals, were first completely depleted of anti-DNA and of DNA by affinity chromatography. The suppressive capacity of equimolar concentrations of the various depleted sera (blocking sera) on target lupus sera were determined. The target sera were from lupus patients with known DNA-binding capacity. Blocking sera from inactive SLE suppressed the binding of autologous anti-DNA antibody to [(3)H]DNA (n = 19,P < 0.01). Blocking sera from active SLE (n = 19), as well as human serum albumin, did not suppress. Sera from normal donors who had no contact with lupus patients or with lupus sera did not suppress (n = 14, P > 0.5), whereas those from normal donors who had contact with lupus patients or sera did suppress the binding (n = 5,P < 0.02). The anti-anti-DNA antibody suppressive activity in the inactive lupus serum was shown to be localized within the F(ab')(2) portion of immunoglobulin (Ig)G and could not be removed upon adsorption by normal human gammaglobulin. Furthermore, immune complexes could be detected by a Clq binding assay when the inactive lupus blocking sera were incubated with the anti-DNA antibody containing target sera. The specificity of the suppressive serum factor was shown by its inability to block the binding of tetanus toxoid to antitetanus antibody and its ability to block the binding of DNA to F(ab')(2) fragments of active lupus IgG. Regulation of serum anti-DNA antibody levels by anti-antibodies could induce and maintain disease remission in lupus patients and prevent disease expression in normals.

Antibodies, Antinuclear↗

Serial studies of autologous antibody reactivity to melanoma. Relationship to clinical course and circulating immune complexes.

The low titer and incidence of autologous antibody to melanoma has hampered its evaluation. Through acid dissociation and ultrafiltration of serum, we have been able to augment the autologous immune response in 9 of 10 patients studied. This result suggests that autologous antibody is present in most patients with melanoma, but is obscured by circulating antigen and the formation of immune complexes. Because native antibody and antibody derived from circulating immune complexes are produced by the host against physiologically relevant antigens, correlations can be made to clinical course. Serological studies of three patients with melanoma were performed with serum samples obtained over many months; these studies demonstrated correlations with tumor progression and clinical course. Serial serologic studies may yet provide one of the better ways to evaluate these relationships. They have the advantage of detecting transient events that may occur with the inception of metastatic disease or autoimmune phenomena, and of avoiding the difficulties encountered in comparing antibody responses between different individuals.

Animals↗

Some studies on the polyethylene glycol turbidity method for detecting immune complexes in serum.

A rapid and simple method for detecting circulating immune complexes based on turbidity measurements following polyethylene glycol precipitation was studied with regard to its suitability as a routine assay in clinical laboratories. This method was found to have an acceptable degree of precision provided the temperature was carefully controlled. The mean value obtained with a group for 70 blood donors was 0.09 (SD 0.05) and the 90th percentile value was 0.16. There was no significant difference between values obtained from groups divided on the basis of age or sex. Of 70 diabetic sera assayed by the polyethylene glycol turbidity method, 20% gave positive values although only 10% were strongly positive. The corresponding figures for the solid phase Clq binding method were 15.7% and 14.3%, respectively. Correlation between the two methods was poor. It was concluded that although both methods have a similar likelihood of detecting immune complexes in randomly selected diabetics, it is probable that different immune complexes were being detected.

Antigen-Antibody Complex↗