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PubMed1986

Properties and reactivity of immune complexes in rheumatoid synovial fluid.

Fractionation of immune complexes (IC) from rheumatoid synovial fluid revealed the presence of three different fractions of IC. The largest molecular weight form, fraction I (above 1000 Kdaltons) was predominately composed of IgG and IgM and contained both IgM-RF and IgG-RF. The other IC, fraction II (480 Kdaltons) and fraction III (330 Kdaltons), contained predominately IgG with some IgA and only significant amounts of IgG-RF. All three fractions of IC can bind Clq and stimulate human monocyte prostaglandin E (PGE) production. Fraction I IC bound Clq most readily while fraction III IC were the most effective stimulators of monocyte PGE production. IC stimulation of monocyte PGE production was inhibited by staphylococcus protein A suggesting mediation via activation of Fc receptors. It remains to be determined whether this IC reactivity has any pathologic significance.

Antigen-Antibody Complex↗
PubMed1981

Clq deposits at the dermoepidermal junction: a marker discriminating for discoid and systemic lupus erythematosus.

Discoid lupus (DL) and systemic lupus erythematosus (SLE) patients have been comparatively evaluated for complement and immunoglobulin deposits at the dermoepidermal junction (DEJ) by immunofluorescence (IF). When IF was positive, Clq deposits were quasi-constantly found in SLE patients with or without skin lesions (90%), while Clq was found in only 29% of the DL patients. Of the 42 DL patients followed-up to at least 2 years, 4 have eventually evolved a systemic disease. In these 4, neither cryoglobulinemia nor significant titers of ANA had been found at the time of presentation. Only 1 of these 4 patients had initially circulating immune complexes (P.E.G) and a positive IF in a normal sunprotected area. Clq deposits at the DEJ were present in all these 4. Of the remaining 38 DL patients, none has progressed to SLE: 8 had had significant titers of ANA, 5 had had circulating immune complexes, and 3 others had had cryoglobulinemia. Thus Clq deposits in DL cases are associated with a relatively high incidence of eventual systemic disease. Taken together, these data suggest that Clq deposits in skin may be a marker for systemic lupus.

Adolescent↗
PubMedDate not supplied

More homologies among the vertebrate plasma proteins.

Many of the proteins of vertebrate blood plasma share common ancestry. As more sequences are reported, the network of relationships continues to expand in unexpected directions. Computer analysis now reveals that a minor plasma protein of unknown function, gamma-trace protein, is related to the kininogen family. Some other possible relationships have been uncovered also, including a resemblance between the histidine-rich hinge regions of high molecular weight kininogen and hemopexin and between Factor VIII and Von Willebrand Factor.

Animals↗
PubMed1983

Evidence for histidine residues in the immunoglobulin-binding site of human Clq.

The immunoglobulin-binding activity of subcomponent Clq of human complement is lost following treatment with diethylpyrocarbonate; the inactivation showed first-order kinetics with respect to time and modifier concentration. Soluble IgG oligomers protected Clq against diethylpyrocarbonate modification. Treatment of modified Clq with hydroxylamine resulted in an 85% recovery of its ability to bind to aggregated immunoglobulin. The inactivation process was associated with modification of 12.1 +/- 0.7 histidine residues per Clq molecule. These data are consistent with the presence of histidine residues in the immunoglobulin-binding sites of Clq; these residues may participate in ionic interactions with the carboxyl groups known to be in the Clq binding site of IgG.

Chemical Phenomena↗
PubMedDate not supplied

Protracted necrotizing pharyngitis associated with an acquired defect of neutrophil chemotaxis in multiple myeloma.

A 69-year-old man presented with protracted necrotizing pharyngitis requiring prolonged antibiotic therapy. During immunologic evaluation he was found to have IgA multiple myeloma, low complement component C1q and extrinsic defect of neutrophil chemotaxis. The severity of his pharyngitis correlated with myeloma activity implying a causal relationship. The characteristics of the illness strongly suggest that it is related to the acquired defect in neutrophil chemotaxis. This case represents a previously undescribed infectious complication of multiple myeloma.

Aged↗
PubMed1977

Hydroxyproline fractions in serum and urine of rats during wound healing.

Total hydroxyproline in urine and free hydroxyproline, free and peptide hydroxyproline and protein bound hydroxyproline in serum are measured during wound healing in rats. The free and free+peptide fractions vary in concert with each other and with urine hydroxyproline. Protein bound hydroxyproline fractions take a very different course and behave as an acute phase reactant. The results suggest that protein bound hydroxyproline does not mirror collagen turnover but may be more relevant to C1q or complement metabolism.

Animals↗
PubMedDate not supplied

A Clq solid phase microenzymatic assay for the detection of soluble immune complexes.

The solid phase Cl1-binding assay has been adapted to an enzymatic micromethod in which alkaline phosphatase labeled soluble Staphylococcus aureus protein A is used in place of the second antibody. The assay, which is run in microtiter plates, provides a rapid, sensitive (0.030 mg/ml of human heat-aggregated IgG detected) and reproducible method for the measurement of soluble immune complexes in a large number of samples. Soluble immune complexes prepared in vitro with bovine serum albumin (BSA) and anti-BSA antibodies on a wide range of antigen to antibody ratios were all detected with this method. When applied to the screening of unselected patient sera, soluble immune complexes were frequently found in systemic lupus erythematosus (52%) and chronic active hepatitis (57%) and in lower percentages in patients with malignant melanoma (28%), rheumatoid arthritis (30%) and essential mixed cryoglobulinemia (17%).

Antigen-Antibody Complex↗
PubMedDate not supplied

Cryoprecipitation. In vitro studies on fibronectin as an independent cryoprecipitagogue.

Fifteen patients affected by essential mixed cryoglobulinemia or secondary cryoglobulins were studied. Fibronectin was detected in the majority of essential mixed cryoglobulinemias, but in a minority of secondary cryoglobulins. In vitro studies gave strong evidence of an interaction between fibronectin and heat-aggregated gammaglobulins. The effects of fibronectin on cryoprecipitation of heat-aggregated gammaglobulins seem to support the independent role of the glycoprotein in the cryoformation mechanism, although its presence does not appear essential for cryoglobulin appearance.

Chemical Precipitation↗
PubMed1988

Use of glutaraldehyde-treated erythrocytes as indicator cells for the identification of the Clq component on the macrophage membrane by a rosette assay.

Glutaraldehyde-treated sheep red blood cells (EGA) form rosettes with macrophages of various origin. The binding of EGA to cell surface is mediated by the membrane associated Clq as demonstrated by the inhibition of EGA rosette formation either after treatment of macrophages with anti-Clq serum or after treatment of EGA with Clq. The results clearly demonstrate that the EGA-binding receptor of macrophage is the Clq component.

Aldehydes↗
PubMed2001

Specific von Hippel-Lindau protein expression of clear cell renal cell carcinoma with "immunogenic" features.

Human clear cell renal cell carcinoma (CCRCC) is characterized by specific von Hippel-Lindau (VHL) gene alterations and immunogenic features. In the present study, the immunohistochemical expression of the von Hippel-Lindau gene protein (pVHL) was compared with the presence of major histocompatibility complex (MHC I-II), tumor infiltrating lymphocytes (TIL) and tumoral immune complexes (TIC) in CCRCC. Native tumor tissues of 132 RCC patients (95 with the common clear cell subtype), diagnosed according to the Heidelberg classification, were obtained for immunohistochemistry. Tumor stainings with pVHL, MHC I-II and tumor infiltrating lymphocytes (T and B lymphocytes, monocytes) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (IgG, IgA, IgM and C1q, C3 complement proteins) were visualized by fluorescent polyclonal antibodies. Immune stainings were semiquantitatively evaluated. Specificity and sensitivity of these markers in relation to the common histological subtype of RCC (CCRCC) were calculated. CCRCC was characterized by specific pVHL expression. At the same time, CCRCC was associated with constitutional MHC I-II expression and highly specific degree of TIL and TIC. It is concluded that specific pVHL expression of CCRCC is frequently associated with immunogenic features. Immunohistochemical analysis aims the initial tumor staging of RCC patients to achieve better patient selection for immunotherapy. However, the association of pVHL expression with the immunogenic CCRCC is statistically relevant, the mechanism and its clinical relevance in immunotherapy still remains to be tested.

Adenocarcinoma, Clear Cell↗
PubMed2004

Serum adiponectin in women with polycystic ovarian syndrome and its relation to clinical, metabolic and endocrine parameters.

UNLABELLED: Several studies have demonstrated that low levels of serum adiponectin are present in obesity, insulin resistance, hypertension and hyperlipidemias. The aim of our study was to determine whether serum adiponectin level is different between patients with polycystic ovarian syndrome (PCOS) and control subjects. We also investigated relationships between various cardiovascular risk factors, levels of serum adiponectin and other hormones, such as androstendione, testosterone, estradiol, DHEAS, sex hormone binding globulin (SHBG), and leptin. We also analysed the correlation between serum adiponectin and free androgen index. Ninety-one women with clinical diagnosed PCOS and 53 healthy control subjects, carefully matched by body mass index (BMI) and age, were enrolled in the study. The fasting blood samples were obtained and all participants underwent an oral 75 g glucose tolerance test. The prevalences of impaired glucose tolerance (IGT), hypertension and hypertriglyceridemia were higher in the PCOS group. PCOS women had increased androgen concentrations and higher free androgen index and decreased level of serum SHBG. Lower serum adiponectin concentrations were observed among cases than in controls (median 13.7 microg/ml vs 17.8 microg/ml, p<0.001) despite being matched by BMI. In the PCOS group adiponectin levels correlated significantly with: BMI (r=-0.32, p=0.002), waist circumference (r=-0.32, p=0.003), waist-to-hip ratio (WHR, r=-0.38, p=0.001), triglycerides (r=-0.31, p=0.007), SHBG (r=0.30, p=0.003) and free androgen index (r=-0.29, p=0.02). In contrast, the adiponectin level does not appear to be related to total testosterone, DHEAS and leptin levels. The adiponectin and SHBG levels were found to be decreased in PCOS women with IGT compared to PCOS women with normal glucose tolerance, but after adjustment by BMI or WHR, the differences were no longer statistically significant. To exclude a possible confounding effect due to a higher prevalence of IGT in the PCOS group, this comparison was repeated for the subgroup of 58 PCOS women and 48 control women after excluding those with IGT. Neither adiponectin nor SHBG were significantly different between those subgroups. Multiple regression analysis revealed that serum adiponectin concentrations were best predicted by WHR, free androgen index and presence of IGT when all patients were considered. In PCOS subjects, the only independent predictor of adiponectin concentrations was glucose tolerance status. CONCLUSIONS: Lower adiponectin levels were observed in PCOS group than in control women, and these differences were probably due to higher prevalence of IGT in these cases.

Adiponectin↗
PubMed1998

Autoantibodies to oxidised low density lipoproteins in IDDM are inversely related to metabolic control and microvascular complications.

Diabetes mellitus is associated with an increased risk of atherosclerosis. The oxidation of low-density lipoproteins (LDL) is considered a key event in the initiation of atherosclerosis. To investigate LDL oxidation in vivo we measured autoantibodies to oxidised LDL (oxLDL) in 94 patients with insulin-dependent diabetes mellitus (IDDM), compared to 27 age-matched, healthy control subjects. Patients and control subjects were screened for autoantibodies using a solid phase ELISA, comparing the binding to oxLDL with that to native LDL (nLDL). In patients with IDDM the oxLDL/nLDL antibody ratio was significantly higher than in control subjects (means+/-SEM: 2.24+/-0.26 vs 1.17+/-0.17, p < 0.03). Antibody-negative patients had a longer diabetes duration (13.5+/-1.3 vs 9.1+/-1.1 years, p < 0.01) and higher actual and mean HbA1c levels compared to antibody-positive patients (8.8+/-0.2 vs 7.9+/-0.2%, p < 0.005 and 8.3+/-0.2 vs 7.7+/-0.2%, p < 0.03; respectively). In patients with a high microangiopathy score, the antibody ratio was lower than in patients without complications (1.04+/-0.10 vs 2.40+/-0.29, p < 0.01). OxLDL specific immune complexes were found exclusively in antibody-negative as compared to antibody-positive patients (18.3 vs 0 %; p < 0.01). Our data demonstrate an inverse relationship between free oxLDL antibodies and the severity of the disease. This apparent paradox can be explained in part by our demonstration of oxLDL immune complexes, masking free antibodies.

Adult↗
PubMed1997

Regressive changes of astroglia in white matter lesions in cerebrovascular disease and Alzheimer's disease patients.

The pathogenesis of white matter lesions, which are frequently found in ischemic cerebrovascular disease and Alzheimer's disease, remains unclear. Using light and electron microscopic immunohistochemistry for glial fibrillary acidic protein (GFAP) as a marker, the present study focused on the role of astroglia which show characteristic morphological alterations. Of 29 brains of patients with cerebrovascular disease and Alzheimer's disease, 4 brains showed extensive swelling and vacuolation of white matter astroglia with their processes disintegrated and beaded (termed clasmatodendrosis). No such cells were observed in 6 control patients. Clasmatodendritic astroglia were not intensely eosinophilic using hematoxylin and eosin staining and included large lipophilic granules in their perikarya. These astroglia were immunoreactive for serum proteins such as immunoglobulins, fibrinogen and complement C3, C1q and C3d, as well as for proteins which are known to increase in reactive astroglia, such as vimentin, alpha-B crystallin, apolipoprotein-E and laminin. Double labeling for GFAP and microglial cell markers indicated that these cells were of astroglial lineage. Immunoelectron microscopy for GFAP revealed that clasmatodendritic astroglia had condensed chromatin, lysosomes and large membrane-bound osmiophilic cytoplasmic inclusions, which corresponded to the lipophilic granules observed with light microscopy. These cytochemical features collectively suggest that clasmatodendritic astroglia incorporate edema fluid and phagocytose cellular debris, and eventually degenerate as a result of cerebral edema.

Aged↗