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Increased IgM and IgM immune complex-like material in the circulation of renal transplant recipients with primary cytomegalovirus infections.

Twelve of 60 consecutive adult recipients of cadaver kidney transplants had increased polyethyleneglycol (PEG) precipitable IgM immune complex-like material in their circulation in the first 4 months after transplantation. All 10 recipients with primary CMV and two of four with secondary CMV infections had significant elevations in PEG precipitable IgM that coincided with rises in their CMV antibody titres. Ultracentrifuge analysis demonstrated two peaks of PEG precipitable material with sedimentation rates of about 20S and 40S. Total IgM immunoglobulin levels also were increased in transplant recipients with CMV infections, but this was less specific and occurred in patients without CMV infections. The Clq binding assay, which is more sensitive for IgG than IgM containing complexes, was positive in only three of 10 patients with primary CMV and none of four with secondary CMV. Granular deposits of IgM, but not IgG, were detected in the glomeruli of six of seven transplants biopsied during CMV infection. The PEG-IgM assay was not influenced by rejection or prednisone therapy. Thus, transplant patients, who develop primary CMV infections, produce elevated levels of circulating IgM and IgM immune complex-like material. These findings may help to differentiate CMV infection from transplant rejection as well as to increase our understanding of the special pathogenic properties of CMV in transplant recipients.

Adolescent↗

[Two possible conformations of the repetitive site of the immunoglobulin G3 hinge region].

Conformational analysis of immunoglobulin G3 (IgG3) hinge region repeating part was performed. In approximation of backbone regular conformations for the case of C2 symmetry (the symmetry axis is perpendicular to S-S bridges and passes through their midpoint) on the basis of total analysis of ring geometry possibilities and estimation of steric conditions, the existence of two conformations with n = 3 (3(10) helix type and polyproline II type) was inferred. A possible role of these conformations in the immunoglobulin functioning was discussed.

Amino Acid Sequence↗

Identification of components of IC purified from human sera. II. Demonstration of mycobacterial antigens in immune complexes isolated from sera of lepromatous patients.

Immune complexes have been purified from sera of patients with lepromatous leprosy, using solid phase conglutinin and analysed by SDS-PAGE. Some of their components have been immunologically identified after electrophoretic blotting on nitrocellulose. First, immunoglobulins, complement components (C1q, C1s, C3) and CRP were found in IC. Secondly, one mycobacterial antigen of 67 kD was directly identified in IC while two other components (20 kD and 14.4 kD) of possible M. leprae origin were also found in IC. This study suggests that lepromatous patients develop a good antibody response against some M. leprae antigens (33 kD and 12 kD), which are rapidly eliminated from circulation, while other M. leprae antigens (e.g. 67 kD) can persist in relative antigen excess, within circulating IC.

Antigen-Antibody Complex↗

[Immunofluorescent optical detection of HBSAG in the human small intestine in chronic aggressive HBSAG-seronegative hepatitis with diarrhea].

HBsAg has been detected by direct immunofluorescence in the small bowel biopsy specimen of a 16 a old male patient with diarrhoea and HBsAg seronegative (autoimmune) chronic aggressive hepatitis. HBsAg was localized focally in apical regions of intestinal crypts, in the cytoplasm, and on their cell membranes as well as in vascular endothelium. Pretreatment of the tissue sections with unlabelled anti-IgM, anti-IgG, and fresh human serum did not block the direct staining for HBsAg. Antisera to IgG, the complement components C1q, C4, and C5 as well as to fibrinogen and FITC-Staphylococcus protein A were bound in a similar manner. Therefore, it may be reasonable to assume, that hepatitis B virus can infect the human small intestine and could be regarded as one of rare gastroenteritic viruses.

Adolescent↗

Differential precipitation of the Clq subcomponent of the first complement component (C1) by polyethylene glycol from normal human serum and sera of patients with collagen diseases.

Sera were, under strictly standardized conditions, centrifuged in the presence of 0-5% PEG and the Clq concentration in the precipitates was measured by radial immunodiffusion. The presence of circulating immune complexes and rheumatoid factor(s) resulted in a shift of Clq precipitation to lower PEG concentrations. Clq precipitation at 1.5% PEG was shown to be specific for sera containing immune complexes. Under similar conditions addition of aggregated IgG to normal human serum gave rise to Clq precipitation directly proportional to the amount of aggregated IgG. Precipitation of endogenous Clq at 1.5% PEG and assay by radial immunodiffusion may therefore be useful for the detection and quantitation of immune complexes in human serum.

Antigen-Antibody Complex↗

[Immunofluorescence studies in stomach and breast carcinomas and benign breast diseases].

A study was made for localization of immunoglobulins and complement components in human malignant tumour tissues. There were not observed characteristical deposits on tumour cells. In a 2nd investigation where indirect immunofluorescence method was used, autologous antibodies to tumour material were not detectable. Only with anti-C3-technique, 2 sera from patients with breast cancer and 1 serum from a patient with mastopathia reacted with breast cancer tissue (allogenic system). However, a lot of autoantibodies of different specifity could be found in sera of tumour patients. The problems of unspecific staining and the occurrence of autoantibodies in tumour sera were discussed.

Antibodies, Neoplasm↗

Small albumin-immunoglobulin complexes in patients with liver disease.

Circulating immune complexes (CIC) with a molecular weight (M.W.) of 1.4-1.6 x 10(6) were observed in patients with liver disease. CIC containing abnormal albumin were found in patients with chronic active hepatitis. The abnormal albumin from CIC displayed an apparent M.W. of 105-110,000 on Sephadex G-100 and Sepharose 6B column chromatograph before reduction, and only 50,000 on reduced sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). It is postulated that abnormal albumin contained within CIC may be a dimeric-S-S-linked small albumin (sAlb-S-)2. Immunoglobulins in the CIC containing (sAlb-S-)2 were identified as IgM and IgG. Based on the constituents of CIC and their M.W., the assumed molecular formula of CIC is (IgM)1 (sAlb-S-)2 (IgG)3. Cause and effect of these CIC in liver disease, especially a possible role of altered host components in the initiation of autoimmune reactions, are discussed.

Antigen-Antibody Complex↗

Circulating immune complexes in Behçet's disease.

The levels of circulating immune complexes (CICs) were investigated in the patients with Behçet's disease by Clq solid-phase enzyme immunoassay. A significantly higher level of CICs was observed in the patients than in the control group. Concerning the correlation between the levels of CICs and the stages of the ocular attack, the levels were significantly higher in the preattack stage and the early stage of the attack than in the late stage and the remission phase. A high level of CICs was associated with the patients of the fulminant form of ocular attacks. These results suggest that immune complexes may play a role in the development of the ocular attack of Behçet's disease.

Adult↗

Henoch-Schoenlein syndrome: a clinical and morphological study of renal biopsies.

Twenty-four patients, 12 children and 12 adults, with the Henoch-Schoenlein syndrome had their renal biopsy specimens studied by light and electron microscopic and immunofluorescent antibody techniques. The principal glomerular lesion was a focal and segmental proliferative glomerulonephritis in 15, a diffuse proliferative glomerulonephritis in 6 and a animal or minor change lesion with mesangial hypertrophy in 3 cases. The proliferation of the cells was mainly mesangial. Renal biopsies taken earlier in the course of the disease showed a greater number with a focal lesion. Electron dense deposits with cellular proliferation and increased matrix were seen in the mesangium. Less frequent subendothelial and occasional subepithelial deposits were found. Capillary loop changes were seen more frequently in the later stages of the disease. Heavy deposits of IgA were found in the mesangium in all cases, and less intense deposits of IgG in 60%. beta 1 C globulin and fibrinogen were found in 80% and IgD and IgM less frequently. Complement activation was via the alternate pathway as early complement components C1q and C4 were absent. Overt allergies, streptococal infections and the HBsAg could not explain the pathogenesis of the disease. Henoch-Schoenlein syndrome is a chronic disease of the mesangium; only 5 patients showed complete recovery, 15 had persistent microscopic hematuria and 3 died or developed renal insufficiency within 8 years. The prognosis was worst with diffuse proliferative glomerulonephritis, widespread focal glomerulonephritis or epithelial cresents formation.

Adolescent↗

Talwin addict nephropathy.

Three patients with a 2-3 year history of parenteral abuse of pentazocine hydrochloride (Talwin) developed membranoproliferative glomerulonephritis type I. Clinical presentation included nephrotic syndrome, microscopic hematuria, and hypertension. Tissue studies disclosed 1+ to 4+ mesangial and subendothelial deposits of immunoglobulins (predominantly IgM) and complement components C1Q, C3 and C4 with focal reduplications of glomerular basement membranes. Glomerular C3 receptor studies performed on one patient demonstrated diffuse loss of receptor activity correlating with localization of immune deposits. Serum studies showed decreased levels of C3, elevated levels of IgM (greater than 2 SD) (three patients) and circulating immune complexes (two patients). Repeated blood and urine cultures were negative. Immune mechanisms may be involved in the pathogenesis of Talwin addict nephropathy.

Adult↗