Circulating immune complexes in cervical cancer patients as detected by C1q binding

In a retrospective study in women with cervical cancer, circulating immune complex levels were measured by radioimmunoprecipitation with 125I-C1q. Sera from 46 patients with cervical cancer and 35 normal controls were examined. Significantly higher levels of immune complexes were detected in cancer patients compared with controls. Mean value of binding capacity in patients was 49.8%, and by contrast, in the controls was 27.4% (two-tail test = 0). Increases in tumor mass were associated with high levels of circulating immune complexes. The presence of immune complexes in circulation statistically correlated with disease activity, however, the assay used still had limited value for diagnosis or aiding in therapeutic decisions. Nevertheless, the future holds promise for such uses.     

Detection of immune complexes in unheated sera by modified 125I-Clq binding test. Effect of heating on the binding of Clq by immune complexes and application of the test to systemic lupus erythematosus.

The 125I-Clq binding test was modified in order to allow for the detection of immune complexes in native unheated human serum. Indeed, heat-inactivation (56 degrees, 30 min) was found to reduce the Clq-binding activity of immune complexes mixed with native serum. This effect was not observed when EDTA was added to the native serum before mixing the immune complexes. The modified 125I-Clq binding test was performed in two steps: first, the tested native serum sample was incubated for 30 min at 37 degrees C with 0.13 M EDTA in order to prevent the integration of 125I-Clq into the intrinsic Clqrs complex, second, 125I-Clq and polyethylene glycol (final concentration 2.5%) were added to this mixture, and further incubated for 1 hr at 4 degrees C. Under these conditions, free Clq remained soluble whereas Clq bound to macromolecular complexes was precipitated. The competitive effect of intrinsic Clq and the interference of other substances such as DNA or bacterial LPS were very limited. The modified Clq binding test was applied to the clinical investigation of 44 patients with systemic lupus erythematosus; and increased Clq binding activity (Clq-BA) was observed in 91% of the samples. The level of Clq-BA was found to be significantly correlated to the DNA-binding capacity and to the decrease of the level of some complement components.     

Activation of the binding of C1q to immune complexes by zinc

ZnSO4 promotes the binding of C1q to immune complexes over the same concentration range (10(-5)-10(-4) M) that it inhibits binding of C1 to cell-bound immunoglobulin [Biochem. Biophys. Res. Commun. (1981) 103, 856-862]. At higher concentrations (10(-3)-2 X 10(-2) M) ZnSO4 inhibited the binding of C1q to immune complexes, [Ki = (6 +/- 2) X 10(-3) M]. This inhibition could be correlated with a ZnSO4-induced change in the tryptophan fluorescence of C1q [delta F 25%, Kd = (9.9 +/- 1.0) X 10(-3) M].     

Differences among immune complexes: association of C1q in SLE immune complexes with renal disease

Studies that made use of multiple assay systems demonstrated increased levels of immune complexes (IC) in patients with systemic lupus erythematosus (SLE), but no consistent correlations of IC concentration to patterns or activity of disease have been observed. Furthermore, consistent associations between qualitative differences in IC and disease manifestations have been elusive. IC interaction with erythrocytes and mononuclear phagocytic cells is another variable in SLE that may also mediate some of the biological effects of IC. The present report concerns studies of the composition of purified IC obtained from individuals with SLE and other rheumatic diseases; a 64,000 dalton component identified as the A-B subunit of C1q was detected in purified IC from 27 of 51 SLE patients (53%). The presence of this 64,000 dalton component was not related to either IC concentration or to the serum C1q level. However, the presence of the C1q component in isolated SLE IC did correlate with the presence of renal disease (p less than 0.02). These observations are interpreted relative to a recently described kinetic model of IC clearance.     

Clinical usefulness of estimation of serum fructosamine concentration as a screening test for diabetes mellitus.

Fructosamine, a putative measure of serum glycosylated proteins, was measured in 74 subjects referred for oral glucose tolerance tests. A normal range (mean (2 SD] of 1.6 (0.4) mmol/l (40(10) mg/100 ml) derive from results obtained in 83 healthy non-diabetic volunteers permitted the detection of 15 out of 17 (88%) subjects with proved diabetes and yielded only five (9%) false positive diagnoses. Fructosamine concentrations correlated significantly (p less than 0.001) with fasting plasma glucose concentrations (r = 0.76) and glycosylated haemoglobin concentrations (r = 0.70). A longitudinal study suggested that fructosamine concentration was an index of intermediate term (one to three weeks) blood glucose control. Fructosamine concentration was not related to uraemia and did not depend on albumin or total protein concentrations, provided that serum albumin concentrations remained above 30 g/l. Estimation of fructosamine concentrations is a fully automated procedure and may provide a simple means of screening for diabetes mellitus.     

Conformational changes in C1q after binding to immune complexes: detection of neoantigens with monoclonal antibodies

The formation of neoantigens within the C1q molecule after the binding of C1r and C1s to C1q and the binding of C1q to immune complexes is described. The neoantigens were detected by different monoclonal anti-C1q antibodies. This immunochemical study supports the hypothesis drawn from functional studies that the activation of the classical C pathway results from conformational changes within the C1q molecule leading to the activation of C1r and subsequently C1s.     

The role of serum fructosamine as a screening test for gestational diabetes mellitus

The serum fructosamine concentration indicates the degree of glycation of serum proteins, particularly albumin, and reflects an average blood glucose level over the previous 1-3 weeks. Serum fructosamine, glycated haemoglobin (HbA1c), total serum protein, serum albumin, fasting plasma glucose and oral glucose tolerance test (OGTT) have been measured in 127 healthy control subjects, 102 type 1 and 152 type 2 diabetes mellitus patients and 106 nondiabetic pregnant women. Fructosamine concentration of 2.24 +/- 0.16 and 3.21 +/- 0.41 mmol/l (mean +/- S.D.) has been found in control subjects and diabetics respectively (P less than 0.001). During the second trimester a significantly lower fructosamine level (1.92 +/- 0.21 mmol/l) has been found in pregnant women, most likely due to the low serum albumin concentration (31.35 +/- 3.97 g/l). None of them had a fructosamine level above the normal limit of 2.55 mmol/l. On the other hand, 12 pregnant women showed a disturbed OGTT with normal fructosamine. If the serum fructosamine concentration was adjusted for 40 g/l albumin, then a mean fructosamine of 2.16 +/- 0.24 mmol/l was found in patients with gestational diabetes. Our results show that serum fructosamine has a similar diagnostic value as HbA1c for non-pregnant adults, but neither can replace OGTT for the diagnosis of gestational diabetes.     

Circulating immune complexes in the pathogenesis of recurrent erysipelas

The dynamics of circulating immune complexes (CIC) in comparison with the level of SH-groups of serum deproteinate and other characteristics of cell-mediated and humoral immunity (the reaction of the inhibition of antibodies, the levels of T-cells and their main subpopulations) was studied in 103 erysipelas patients and in 46 persons having had the disease at the acute period of this infection and at the periods between relapses. The elevated levels of CIC and SH-groups of serum deproteinate were found to be directly correlated with the inhibition index. The study showed that, as a rule, in patients with the elevated level of CIC the frequently relapsing form of erysipelas, accompanied by the formation of relative hypersuppressor-type secondary immunodeficiency and by a decrease in the functional activity of dermal macrophages, was observed.     

Evidence for increasing prevalence of diabetes mellitus in childhood.

The prevalence of diabetes mellitus among the cohort of children in the Child Health and Education Study studied at age 10 was 1.3/1000. Comparison with prevalences found in the two previous British birth cohort studies suggested that the prevalence of diabetes is doubling roughly every decade. The data suggested that childhood diabetics are a socially advantaged group. These findings have important implications and should be taken into account by health service planners if the needs of these children are to be met in the future.     

Circulating immune complexes in the diagnosis of Mycoplasma pneumoniae infection

The possibility of detecting M. pneumoniae antigen and antibodies to it, incorporated into immune complexes, in the sera of patients with acute pneumonia by means of erythrocyte diagnosticums was studied, and the immunological characterization of these complexes was made. In patients with mycoplasmal pneumonia M. pneumoniae antigen and specific antibodies, both free and incorporated into immune complexes, were found to circulate in the blood. In children, antigenemia was detected twice as frequently as in adults. Dissociated M. pneumoniae antigens had different molecular weight, their location on the gel chromatogram of the serum being in fractions 7S and 19S. The dissociation of immune complexes permits the detection of M. pneumoniae antigen and antibodies to it in a bound state by means of the passive hemagglutination test, thus increasing the frequency of positive results in the diagnosis of M. pneumoniae infection.     

Circulating immune complexes in cerebrospinal fluid of patients with tuberculous meningitis.

Circulating immune complexes (ICs) were isolated from cerebrospinal fluids (CSFs) of patients with tuberculous meningitis (TBM), non-tuberculous neurological diseases by a polyethylene glycol (PEG) precipitation method. Mycobacterium tuberculosis antigen 5 was detected in CICs of 30% patients with TBM, by sandwich ELISA. CIC level decreases during antituberculosis chemotherapy and therefore its detection can provide a method to monitor the therapeutic schedule in patients with TBM.     

Quantitative analysis of the interaction between immune complex and C1q complement subcomponent. The role of interdomain interactions in rabbit IgG in binding of C1q to immune precipitates.

A novel method was developed for the analysis of the interaction of large multivalent ligands with surfaces (matrices) to analyse the binding of complement subcomponent C1q to immune precipitates. Our new evaluation method provides quantitative data characteristic of the C1q-immune-complex interaction and of the structure of the immune complex as well. To reveal the functional role of domain-domain interactions in the Fc part of IgG the binding of C1q to different anti-ovalbumin IgG-ovalbumin immune complexes was studied. Immune-complex precipitates composed of rabbit IgG in which the non-covalent or covalent bonds between the heavy chains had been eliminated were used. Non-covalent bonds were abolished by splitting off the CH3 domains, i.e. by using Facb fragments, and the covalent contact was broken by reduction and alkylation of the single inter-heavy-chain disulphide bond. The quantitative analysis of the binding curves provides a dissociation constant (K) of 200 nM for the interaction between C1q and immune precipitate formed from native IgG. Surprisingly, for immune precipitates composed of Facb fragments or IgG in which the inter-heavy-chain disulphide bond had been selectively reduced and alkylated, stronger binding (K = 30 nM) was observed. In this case, however, changes in the structure of the immune-complex matrix were also detected. These structural changes may account for the strengthening of the C1q-immune-complex interaction, which can be strongly influenced by the flexibility and the binding-site pattern of the immune-complex precipitates. These results suggest that domain-domain interactions in the Fc part of IgG affect the segmental mobility of IgG molecules and the spatial arrangement of the immune-complex matrix rather than the affinity of individual C1q-binding sites on IgG.     

Identification of a type 1 insulin-like growth factor binding protein (IGF BP) in serum from rats with diabetes mellitus

Circulating insulin-like growth factor binding protein (IGF BP) activity is increased in animals with streptozotocin-induced diabetes. Separation of BPs by SDS/PAGE for ligand and immunoblot analysis revealed that a 32,000 molecular weight BP is present and increased in diabetic serum. This BP is immunologically distinct from the low molecular weight fetal rat BP (rBP2) and is related to the human amniotic fluid BP (hBP1) that is increased in patients with insulin dependent diabetes mellitus.     

树突细胞的免疫耐受及其在Ⅰ型糖尿病中的作用

树突细胞(dendritic cells,DCs)通过将抗原提呈给初始T淋巴细胞(native T lymphocyte),从而诱导CD8~+细胞毒性T细胞(cytotoxic T cell,CTL)和CD4~+效应T细胞的分化并启动获得性免疫应答。此外DCs在诱导并维持免疫耐受方面也具有重要作用。现就DCs的免疫耐受机制及其在I型糖尿病(type 1 diabetes mellitus,T1DM)中的作用的研究进展作一综述,为T1DM等自身免疫性疾病及移植免疫疾病的细胞免疫治疗提供新思路。