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PubMed2002

The effect of high salt concentration on detection of serum immune complexes and autoantibodies to C1q in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the binding of immune complexes and anti-Clq in systemic lupus erythematosus (SLE) sera to Clq and to the purified collagen-like region of Clq (CLR) in high and physiologic NaCl concentrations. METHODS: Sera from patients with SLE were tested for binding of IgG to Clq and to CLR in physiologic (0.15 M NaCl) or high (1.0 M NaCl) salt concentration. Sera were ultracentrifuged to separate monomeric IgG and high molecular weight IgG (immune complexes), and fractions were tested for binding to C1q and to CLR in the presence of physiologic or high salt concentrations. RESULTS: Decrease in binding of immune complexes to Clq in the presence of high salt ranged from 0 to 96.8%, with a median of 48.4%. Decrease of the binding of monomeric IgG to C1q in the presence of high salt ranged from 2.2 to 74.3%, with a median of 46.2%. Binding of monomeric autoantibodies to CLR also was decreased by high salt. Nevertheless, anti-Clq measured by binding to CLR in physiologic salt correlated highly with the binding to Clq in both physiologic (r = 0.978) and high salt (r = 0.983). CONCLUSION: Clq-binding of immune complexes in SLE sera is not uniformly abrogated by high salt and binding of autoantibodies to CLR is variably reduced by high salt. Binding of IgG to Clq in high salt correlates with but is not equivalent to quantifying these autoantibodies by binding to CLR.

Antigen-Antibody Complex↗
PubMed1982

IgA containing immune complexes in dogs bearing a spontaneous mammary adenocarcinoma.

Sera from dogs with mammary adenocarcinoma were assessed for the presence of immune complexes (IC) and the physicochemical composition of these complexes was investigated. Employing 125I-anti-canine IgG as indicator, elevated levels of C1q binding IgG were detected in sera of dogs with mammary adenocarcinoma. Polyacrylamide gel electrophoresis (PAGE) analysis of IC isolated by G-200 fractionation and protein A affinity chromatography revealed the presence of a dense polypeptide band corresponding to the alpha chain of IgA which was present in the mammary adenocarcinoma sera but not in normal dog sera or sera from dogs with other tumours. Employing monospecific radiolabelled anti-canine IgA as indicator in solid phase C1q binding radioimmunoassays, significantly elevated levels of C1q binding IgA were detected in five of eight mammary adenocarcinoma sera but not in sera of normal dogs or other tumour bearing dogs (P less than 0.05). Sera from mammary adenocarcinoma bearing dogs treated with 5% polyethylene glycol (PEG) and subjected to sucrose density gradient ultracentrifugation revealed IgA containing IC in fractions greater than 7S to greater than 19S. Findings suggest that IC are present in sera of dogs with mammary adenocarcinoma and that that IgA is a major and unique component of these complexes and, hence, may play a significant role in the development and evolution of the canine immune response to mammary adenocarcinoma.

Animals↗
PubMed1983

Types of immune complexes in the ascitic fluid of women with carcinoma of the ovary.

Immune complexes with C1q-fixing properties and those precipitable by polyethylene glycol (PEG) were detected in ascitic fluid from patients with advanced ovarian cancer. The ascitic fluid from 42 of 58 patients (72%) contained these complexes. A positive result with the C1q assay was obtained in 41% of patients, whilst with the PEG assay a positive result was obtained in 59% (50% in the IgM, 36% in the IgG, and 14% in the IgA fraction). The highest mean level of PEG-precipitable complexes was in the IgG fraction (11.4 mg/100 ml) and lowest in the IgA fraction (3.3 mg/100 ml). These results indicate that gram quantities of the immune complexes may be isolated from the large volumes of ascitic fluid usually present in ovarian cancer. Further studies of ascitic fluid may thus provide data on the nature of the immune responses in these patients.

Antigen-Antibody Complex↗
PubMed1984

Sequential determination of circulating immune complexes during progressive and regressive phases of mouse mastocytoma.

Circulating immune complexes were determined by 125I-C1q-binding and Raji cell-binding sequentially during distinct phases of progression and regression of a weakly immunogenic murine tumour. No increase in levels of circulating immune complexes was found at any time during tumour development, although reference complexes formed between tumour cell membrane antigens and a murine histocompatibility antigen-directed alloantibody were easily detected by both tests. These findings parallel the absence of humoral antibody during tumour development but are in some contradiction to the pronounced B cell proliferation which was observed in this tumour model. The results add evidence for a more critical evaluation of the role which levels of circulating immune complexes might play in tumour diagnosis and prognosis.

Animals↗
PubMed1993

Thermodynamic studies of the collagen-like region of human subcomponent C1q. A water-containing structural model.

Thermal transitions of Clq were investigated by methods of differential scanning calorimetry, circular dichroism and fluorescence. The melting curves of Clq display two pronounced heat absorption peaks with enables determination of the thermodynamic parameters characterizing each transition. The low temperature peak was assigned to melting of the Clq collagenous part. Analysis of the data has revealed unusual, as compared with the monomeric collagen molecules, thermodynamic features of the Clq collagenous part: (1) higher thermal stability strongly dependent on pH; (2) less linear co-operative regions; and (3) a noticeable change in the partial specific heat capacity (delta Cp) in contrast to both the monomeric collagen and the collagen fibrils. This unusually large delta Cp value suggested a conclusion that the fibril-like endpiece of Clq may have a cavity filled with ice-like ordered water molecules.

Calorimetry, Differential Scanning↗
PubMed1985

Immunohistological investigations of PAS-negative globular intracisternal hyalin in human liver biopsy specimens.

Eight liver biopsy specimens from five patients with PAS-negative intracisternal hyalin were investigated by immunofluorescence for: (1) immunoglobulins (Ig) G, A, M, D, E; (2) light chains (kappa and lambda); (3) complement components C1q, C4, C3c, C5, C9; (4) C1-inactivator; (5) C3-activator; (6) alpha 1-antitrypsin; (7) alpha 1-antichymotrypsin; (8) plasminogen; (9) fibrinogen; (10) fibrinogen breakdown products D and E; (11) fibronectin; (12) prealbumin; (13) albumin; (14) betalipoprotein; (15) apolipoprotein; (16) alpha 1- and alpha 2-glycoprotein; (17) cholinesterase; (18) ceruloplasmin; (19) haemopexin; (20) myoglobin; (21) placenta lactogen; (22) transferrin; (23) actin; (24) myosin; (25) cathepsin D; and (26) hepatitis B surface and core antigens (HBsAg and HBcAg). The globules reacted significantly with antisera against C3c (three patients), C4 (three patients), C3-activator (one patient) and fibrinogen (two patients). The cause of the protein accumulation is not clear. Serial studies indicate the possibility of a disturbance of protein secretion and an as yet unidentified immune complex disorder.

Complement C3↗
PubMedDate not supplied

Semisynthetic human insulin: biologic and immunologic activity in newly treated diabetic subjects during a six-month follow-up.

Biologic and immunogenic activities of semisynthetic human monocomponent insulins were examined in insulin-dependent diabetic patients (group 1). Patients treated with porcine monocomponent (group 2) and conventional (group 3) insulins were studied for control purposes. The patients were examined before the beginning of insulin treatment and for a 6-mo follow-up period. The data collected during the study show that insulin antibody levels were significantly lower in group 1 than in groups 2 and 3. Furthermore, the prevalence of immune complexes assays with the C1q solid phase technique failed to reveal any differences between the three groups. When the conglutinin binding test was used, the prevalence of immune complexes showed a slight but not significant reduction in group 1 and a significant increase in group 3. The metabolic control was similar in the three groups during follow-up and the insulin requirement was lower, but not significantly, in group 1 than in groups 2 and 3. These data suggest that with human monocomponent insulins equivalent glycemic control may be achieved at similar doses than those required with porcine monocomponent insulins. Furthermore, human insulin is the least immunogenic of the present available insulins.

Adult↗
PubMed1983

Immune complexes in normal subjects.

Immune complex (IC) levels were measured in normal subjects using the C1q solid phase, C1q deviation, C1q binding and polyethylene glycol precipitation assays. Significant changes in IC levels were seen in normals with each of the assays but the pattern of variation was not consistent between assays or subjects or in the same subject from day-to-day. There were no consistent changes with meals, time of day, exercise or the prior administration of prednisone. Low levels of IC appear to be normal in plasma but the variation in IC levels is not explained. Normal IC may well comprise mixtures of non-specific immunoglobulin aggregates, rheumatoid factor-immunoglobulin complexes, idiotype-anti-idiotype complexes as well as specific antibody complexes with antigens from food, infective agents and other sources.

Adult↗
PubMed1986

In vivo reduction of circulating C1q binding immune complexes by intravenous gammaglobulin administration.

Six patients with systemic lupus erythematosus were treated with high-dose intravenous gammaglobulin. Immunological parameters were studied and included solid-phase immune complex determinations, quantitative immunoglobulins G, A, and M, as well as C3 and C4 concentrations. Pretreatment values of circulating immune complex concentrations as measured by either C1q binding or anti-C3 binding assays were elevated in all patients. Posttreatment values showed reductions in all C1q binding immune complexes (p less than 0.01) and anti-C3 binding immune complexes also decreased in 5 out of 6 patients. These assays are described in detail and were also used to define in vitro interactions between the intravenous gammaglobulin preparation and heat-aggregated IgG or sera containing elevated circulating immune complexes. No reduction of immune complex levels were observed when IgG was incubated in vitro with either heat-aggregated IgG or sera with elevated immune complex concentrations. The duration of the in vivo effect and the patients' clinical responses are described. These findings show that high-dose intravenous gammaglobulin administration can reduce certain types of immune complexes in patients with elevated levels of these substances.

Adolescent↗
PubMedDate not supplied

IgG and IgA autoantibodies to C1q in systemic and renal diseases.

Antibodies to the collagen-like region of C1q have been described in patients with SLE and rheumatoid vasculitis. In this study the prevalence of both IgG and IgA C1qAb was assessed in serum samples of 385 patients with different systemic and renal diseases. The results demonstrate that the prevalence of IgG and IgA C1qAb is not restricted to the diseases in which they were originally described. C1qAb can also be demonstrated in patients with MCTD, Felty's syndrome, ankylosing spondylitis, polyarteritis nodosa, mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, glomerulosclerosis, and patients with anti-glomerular basement membrane nephritis. The widespread occurrence of C1qAb of both immunoglobulin classes in systemic and renal diseases may provide insight into the mechanisms that lead to C1qAb formation.

Arthritis, Rheumatoid↗
PubMed1990

Absence of a binding reactivity of human C-reactive protein for immunoglobulin or immune complexes.

Because C-reactive protein (CRP) has been identified as a component of circulating immune complexes from patients with inflammatory diseases, we sought to evaluate a potentially clinically important interaction of this acute-phase protein with immunoglobulin or experimentally-prepared immune complexes in vitro. Highly purified human CRP was incubated with a variety of immunoglobulin substrates, including monomeric immunoglobulin G1 (IgG1), a polyclonal IgG, heat-aggregated IgG, and human serum albumin/anti-serum albumin complexes. We were unable to detect a significant binding interaction of radioiodinated CRP with any of these materials, using either polyethylene glycol (PEG) precipitation or sucrose density gradient ultracentrifugation. In contrast, binding of radioiodinated human C1q to both aggregated immunoglobulin and immune complexes was readily detected by these techniques. Incubation of radiolabeled CRP with serum samples from 22 patients with active inflammatory diseases and high levels of circulating immune complexes disclosed no difference in the amount of PEG-precipitable CRP when compared with serum samples from healthy individuals. However, a radiolabeled commercial preparation of CRP did result in some PEG-precipitable radioactivity after incubation with aggregated IgG. These findings provide no support for a biologically important binding interaction of CRP with immunoglobulin or immune complexes, and they suggest that highly purified preparations of CRP should be used in functional studies of this acute-phase protein.

Acute-Phase Reaction↗
PubMedDate not supplied

Complement activation in acute glomerulonephritis in children.

Serial determinations of complement components (C1q, C4, C3, C5 and factor B) were performed in 32 children with acute glomerulonephritis. Low levels of C3 were found in 30 patients and low levels of C5 in 26. The findings of reduced C1q and/or C4 levels (25 patients) in the first days of the disease suggest activation of the classical pathway. Depressed Factor B levels were found rarely (4 patients). In all patients, the presence of a C3 splitting activity and/of a C3 nephritic factor-like activity was investigated. Both activities were demonstrated in 7 patients whereas in another patient, only C3 splitting activity was noted. A disappearance of both activities was observed in all patients. In 3 patients tested, the C3 nephritic factor-like activity was heat-labile and was therefore not related to true C3 nephritic factor. Both pathways are implicated in the early phases of the disease but continued C3 depression is probably through alternate pathway.

Acute Disease↗
PubMed1991

IgG autoantibodies against C1q are correlated with nephritis, hypocomplementemia, and dsDNA antibodies in systemic lupus erythematosus.

We investigated the association between serum titers of IgG antibodies against C1q (C1qAb) and clinical and laboratory variables of disease activity in systemic lupus erythematosus (SLE). C1qAb were measured by ELISA in serum samples of 88 patients. Thirty patients (34%) had increased C1qAb titers. No correlation between C1qAb titers and a score for general disease activity was found. However, significant positive correlations were found between C1qAb titers and the presence of several clinical and laboratory variables of disease activity. These included nephritis, dermatitis, hypocomplementemia, antibodies against dsDNA, and circulating immune complexes. A negative correlation was found with neurological disease manifestations. The correlations between C1qAb titers and clinical features indicate that the pathogenetic role for C1qAb in certain disease manifestations of SLE deserves further study.

Adolescent↗
PubMed1989

Increased levels of circulating immune complexes are not associated with diabetes in BB rats.

Increased levels of circulating immune complexes (IC) have been described in insulin-dependent diabetic (IDD) patients at the time of diagnosis. The aim of the present study was to test whether the spontaneously diabetic BB rat had changes in IC levels at different ages prior to and at onset of IDDM as compared with diabetes resistant BB rats and normal Wistar Furth rats. The IC levels were related to serum IgG concentration as well as to total peripheral blood lymphocyte counts. Three groups of rats with 12 animals in each were followed: Diabetes-prone, lymphopenic (DP) BB rats with an expected high incidence of diabetes, diabetes-resistant (DR) BB rats from the non-diabetic w-subline, and Wistar Furth rats. Blood samples collected on 12, 22, 29, 43, 71, and 99 days of age were analyzed for IC, detected in a solid phase C1q assay, serum IgG levels, and peripheral blood lymphocytes. Diabetes developed in 8/12 (66%) DP BB rats between 70 and 93 days of age while none of the DR BB rats developed diabetes. The levels of IC tended to increase with age in all three groups of rats and did not differ between DP BB and Wistar rats whereas DR BB rats had significantly higher levels (p less than 0.05-0.01) at all ages. The profile of serum IgG was similar in all rats showing a high level at 12 days of age and a nadir at day 29 followed by an increase from day 43 until the end of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Immune complexes in systemic sclerosis; detection by C1q binding, K-cell inhibition and Raji cell radioimmunoassays.

Thirty-four patients with systemic sclerosis (SS) were investigated for the presence of circulating immune complexes by means of a fluid phase C1q binding assay, K-cell inhibition assay and a Raji cell radioimmunoassay and the results compared with those obtained in 21 patients with systemic lupus erythematosus (SLE) and 52 normal healthy controls. Patients with SS showed an incidence of circulating immune complexes comparable to that found in SLE, with 20 patients (58.5%), giving a positive result with at least one of the assays. The presence of circulating immune complexes in patients with SS was found to be associated with both elevation of serum IgG and IgA levels and extensive visceral involvement by the disease. These findings raise the possibility that circulating immune complexes could be involved in the pathogenesis of SS.

Adult↗
PubMed1982

Ferritin levels and circulating immune complexes in patients with solid tumors.

The level of ferritin and circulating immune complexes (IC) were measured in 53 patients with solid tumors and metastasis using C1q binding assay and the conglutinin binding assay. The level of circulating IC was increased in patients (p less than 0.001) as compared to the controls. Ferritin level was increased in both male and female patients (p less than 0.001), even when the ferritin value was corrected by the aspartic transaminase value, to take for hepatic damage in account. Ferritin was not found to be an important component of immune complexes as IC ferritin did not exceed 2 per cent of total serum ferritin in the 10 patients that were investigated. These results suggest that ferritin levels and circulating IC were increased in patients with solid tumors and metastasis, but that these two parameters are not correlated.

Aged↗
PubMedDate not supplied

[Distribution of aromatic amino acid residues according to the character of their microenvironment and the dynamics of the conformational properties of the protein molecule C1q].

The distribution of aromatic amino acid residues in the Clq molecule according to their microenvironment was studied by the methods of difference thermal and solvent perturbation spectroscopy, fluorescence and chemical modification. Out of the three tryptophan residues located in the globular part of A- chain one residue is completely exposed on the surface, while other two are only partially exposed to a solvent. Chemical modification of tryptophanyls significantly affects the hemolytic activity of Clq, that may evidence for the formation of immunoglobulin-binding sites with participation of A- chains as well as for the location of, at least, one of the three tryptophan residues in A- chain close to the immunoglobulin-binding site or even participation in the formation of the latter. The average rotation relaxation time of tryptophanyls estimated from the data on fluorescence is 210 +/- 10 ns. It specifies mobility of the globular and collagen parts of the molecule.

Amino Acids↗
PubMed2005

C1q nephropathy with asymptomatic urine abnormalities.

We found four cases of C1q nephropathy (C1qN) among a total of 193 pediatric series of first renal biopsies. Among them, 94 biopsies were performed because of asymptomatic urine abnormalities detected by school urinary screening program in Japan; three cases out of these 94 biopsies (3.2%) met the criteria of C1qN. One case out of the remaining 99 biopsies with symptomatic renal diseases (1%) also met the criteria of C1qN. Three cases with asymptomatic onset presenting with mild proteinuria with or without hematuria equally showed histologic features of membranoproliferative glomerulonephritis and showed improvements in urinalysis without corticosteroid treatment. Our data suggest that membranoproliferative glomerulonephritis may be a common histological feature of asymptomatic pediatric C1qN in Japan and that this type of glomerulopathy may follow a relatively good clinical course without steroid therapy.

Adolescent↗