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PubMed1978

Traffic of T and B lymphocytes in the normal spleen.

The occurrence of C3b and C3d complement receptors and of Fc and E receptors in normal splenic tissue was studied in cryostat sections incubated with specific marker cells. Thereby the topographic distribution of T and B lymphocytes in the splenic tissue was mapped: Te lymphocytes are found especially in the periateriolar sheaths, B lymphocytes in eccentric zones around the arterioles. The cells in the splenic pulp carry especially Fc, but also C3b receptors, whereas C3d receptors appear to be specific of lymphocytes. The basic lymphocyte traffic behind the mapped distribution of the lymphocyte subpopulations in the spleen was elucidated by lymphocyte kinetic studies using autologous 51Cr-labelled reinfused lymphocytes. These studies were performed partly on normal persons and partly on splenectomized persons without immune defects. The results indicate the presence of an exchangeable pool of T as well as of B lymphocytes in the spleen, the T cell pool being larger and making up in normals about 30% of the total exchangeable T lymphocyte mass. The matrix for the T lymphocyte pool in the spleen is the periateriolar sheaths. The difference in structure between the lymph nodes and the lymphoid tissue of the spleen, including differences in the distribution of lymphocyte subpopulations, are explained by the special vascular arrangement in the spleen.

Adult↗
PubMed1986

Plasma concentrations of complement split product C3d and immune complexes after procainamide induced production of antinuclear antibodies.

Seventeen patients treated with procainamide for cardiac ventricular arrhythmias were followed for up to 40 weeks. Immunological data as a clue to developing the systemic lupus erythematosus (SLE)-like syndrome was emphasized. Ten patients developed antinuclear antibodies (IgG or IgM), but no increase in the plasma concentration of the complement split product C3d or immune complexes, measured by two different methods, was demonstrated. This finding is in contrast to the high levels of both C3d and immune complexes in SLE. The discrepancy may be caused by a lack of immune complex mediated complement activation by the procainamide induced antibodies, or may be due to a difference in severity of disease. The acetylator phenotype of the patients was determined but due to the low frequency of fast acetylators no comparison of the immunological response of the two phenotypes could be done.

Aged↗
PubMed1986

Circadian and diurnal variation of circulating immune complexes, complement-mediated solubilization, and the complement split product C3d in rheumatoid arthritis.

Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related with low CMS and increased IC levels in the morning, and vice versa in the afternoon. Bed rest and exercise did not influence these fluctuations. The C3d concentration in plasma was increased but showed no diurnal or circadian periodic fluctuations when the levels were corrected for fluctuations in plasma albumin concentration. Clinical assessment by means of pain score exhibited marked variations, with high scores in the morning, and lower in the daytime, whereas measurements of Ritchie's joint index showed no consistent pattern. The circadian variations in CMS, serum IC and clinical parameters indicate the need to collect blood specimens and perform clinical examinations of patients at a fixed time of day.

Adult↗
PubMed1990

Recurrent haemolytic uraemic syndrome and acquired hypomorphic variant of the third component of complement.

In a girl with recurrent haemolytic uraemic syndrome (HUS), persistently low serum levels of C3 were found. Analysis of complement phenotype revealed a hypomorphic variant of C3 Fast in the patient (C3fS) and a normal heterozygous pattern in both parents and the brother (C3FS). Other complement aberrations in the patient were: the presence of a null gene for C4A and C4B and low serum levels of factor H. The father also had partial factor H deficiency. It is hypothesized that the hypomorphic C3 variant may predispose to recurrent HUS. In the acquired forms the role of uraemia in alteration of C3F should be considered.

Complement C3↗
PubMed1986

Histochemical demonstration of mycobacterial antigen, specific antibody and complement in the lesions of tuberculosis.

Lesions were studied histochemically for mycobacterial antigen, its specific antibody and complement in 31 patients with recently-diagnosed tuberculosis. The results were related to a histological spectrum that correlated with bacterial load. The form, localization and persistence of antigen were found to be as significant as the amount. In high-resistant cases, the antigen was mainly soluble, a form which was non-toxic when ingested by macrophages but associated with tissue damage when bound to connective tissue. There was no close contact between plasma cells and antigen. However, in cases with moderate resistance, where plasma cells and antigen intermingled freely, necrosis with karyorrhexis and polymorph infiltration was associated with deposition of antigen, antibody and complement at the same sites, indicating the probability of immune complex formation in these lesions. In low-resistant cases, extensive necrosis was attributed partly to high levels of extracellular antigen. The correlation between immunological circumstances and the manifold forms of necrosis validated these forms as the basis for a histological spectrum in tuberculosis.

Antibodies, Bacterial↗
PubMed1988

The relationship between macrophages and C5b-9 complement complexes in human atherosclerosis.

The relationship between macrophages and the terminal C5b-9 complement complexes was investigated in human arteries affected with atherosclerosis by using monoclonal antibodies and indirect immunoperoxidase, immunogold silver staining, and double-labeling immunohistochemical techniques. Macrophages were found in all the atherosclerotic arteries as immunoreactive deposits with a nucleus, considered as intact cells, or without a nucleus, considered as cell remnants. The double-labeling technique shows C5b-9 deposits partially colocalized on the intact macrophages or on the cell debris of macrophage origin. These data suggest that C5b-9 complement complex may be formed on activated or dying macrophages with subsequent promotion of inflammatory events and progression of the atherosclerotic lesions.

Adult↗
PubMed1987

Biochemical investigations after burning injury: complement system, protease-antiprotease balance and acute-phase reactants.

Seventeen burned patients were investigated--Group I (n=10) with a mean burned area expressed as unit burn standard (UBS) of 69 +/- 24 and Group II (n = 7) with a mean UBS of 23 +/- 8. Blood samples were collected immediately after admission, 6-12 h after injury, during the morning and evening of day 1, and then daily for 2 weeks. This prospective study demonstrated complement activation in vivo in all burned patients, measured by C3d/C3 ratio index which was not related to the extent of the burned surface. A significant protease-antiprotease imbalance, correlated to the severity of burns, was found, leukocyte elastase was increased throughout the observation period, alpha 2-macroglobulin drastically decreased in severely burned patients, and alpha 1-proteinase inhibitor promptly decreased below the normal level in patients with more than 40 UBS. Finally, there was a delayed but then persistent acute-phase reactant protein response involving C-reactive protein, haptoglobin and alpha 1-acid glycoprotein, the concentrations of which reached a plateau on days 6 or 7.

Acute-Phase Proteins↗
PubMed1988

Immunoarchitecture of the "pseudofollicles" of well-differentiated (small) lymphocytic lymphoma: a comparison with true follicles.

Some human malignant lymphomas of the B-cell type have morphologic and immunologic similarities to follicles seen in nonneoplastic reactive lymph nodes. In contrast, a peculiar, vaguely nodular pattern of growth called "pseudonodules" or "pseudofollicular proliferation centers," which is morphologically distinguishable from "true" follicles, is seen in malignant lymphoma, well-differentiated (small) lymphocytic type (WDL). To characterize the cellular components of "pseudofollicles," we undertook a detailed, comparative immunohistologic study of the architectural relationship and distribution of T cells, B cells, and follicular dendritic reticulum cells (DRCs) in reactive follicles, neoplastic follicles, and pseudofollicles. We report several observations on the presence of DRCs and T-cell subset topography in pseudofollicles. Immunohistologic staining for the C3d complement receptor on DRCs revealed that DRC networks associated with "true" follicles were present in all cases of reactive follicular hyperplasia (RFH) and malignant lymphoma, nodular, poorly differentiated lymphocytic type (PDL) studied. Surprisingly, DRC networks were also identified in 8 of 23 cases of WDL. Although the size distribution of DRC network diameters was nearly identical in RFH and PDL, the sizes were markedly diminished in WDL. Immunohistologic staining for Leu 3+ and Leu 2+ T-cell subsets confirmed cellular arrangements in RFH and PDL reported by others. In only 2 of 23 cases of WDL could T cells localized to "pseudofollicles" in frozen tissue sections be identified in a nonrandom arrangement.

Adolescent↗
PubMed1992

Detection and characterization of immunoconglutinins in patients with systemic lupus erythematosus (SLE): serial analysis in relation to disease course.

The levels of IgA, IgG and IgM immunoconglutinins (IK) were assessed in sera from 20 patients with SLE which were followed for 8-month periods. At the time of the exacerbation, IgG IKs were significantly increased to 226 +/- 90 arbitrary units (mean +/- s.e.m.) compared with both the minimum value of 75 +/- 28 in the SLE patients and with 31 +/- 2 in healthy controls (P < 0.05). There was no difference between SLE patients and controls in the levels of IgM and IgA IKs. Most of the SLE patients in this material showed maximal IgG IK levels before exacerbation, but there was no correlation between the clinical disease index and the levels of IgG IK. The specificity of IgG IKs showed a broad diversity for microtitre-fixed C3b, iC3b, C3c and C3dg. The antibodies were of IgG1, IgG3 and in two patients, IgG4 subclass. IgG IKs were correlated to the C3d/C3 ratio which suggested that the IK responses were secondary to C3 activation. In summary, unlike other conditions associated with complement activation where elevated IgM IKs are common, an increase in IgG IK levels was observed. It is possible that this diverging IK response contributes to the pathophysiology of the disease.

Antibody Specificity↗
PubMed1992

Legionella pneumophila lipopolysaccharide activates the classical complement pathway.

Legionella pneumophila is a gram-negative bacterium capable of entering and growing in alveolar macrophages and monocytes. Complement and complement receptors are important in the uptake of L. pneumophila by human mononuclear phagocytes. The surface molecules of L. pneumophila that activate the complement system are unknown. To identify these factors, we investigated the effects of L. pneumophila lipopolysaccharide (LPS) on the classical and alternative complement pathways of normal human serum by functional hemolytic assays. Although incubation of LPS in normal human serum at 37 degrees C resulted in the activation of both pathways, complement activation proceeded primarily through the classical pathway. Activation of the classical pathway by LPS was dependent on natural antibodies of the immunoglobulin M class that were present in various quantities in sera from different normal individuals but were absent in an immunoglobulin-deficient serum obtained from an agammaglobulinemic patient. Additional studies using sheep erythrocytes coated with LPS suggested that the antibodies recognized antigenic sites in the carbohydrate portion of LPS. The ability of LPS to interact with the complement system suggests a role for LPS in the uptake of L. pneumophila by mononuclear phagocytes.

Complement C1↗
PubMed1986

Different patterns of C3 and C4 activation in the varied types of juvenile arthritis.

Quantitative assays for C3 and C4 activation were carried out simultaneously on blood from children with varied types of juvenile arthritis. Factor VIII-related antigen was also measured as an indicator of vascular damage. In active systemic juvenile arthritis, the C4d/C4 ratio was frequently elevated and was usually associated with elevated C3d/C3 ratios and elevated concentrations of factor VIII-related antigen. Children with chronic polyarticular arthritis, no matter which forms of onset they had had, also had increased levels of the C4d/C4 ratio, C3d/C3 ratio, and factor VIII-related antigen, but these were less consistent and were not associated with each other. In contrast, in pauciarticular arthritis there was a uniquely isolated increase in the C3d/C3 ratio. This work implies that there are different mechanisms responsible for complement activation in the different types and at different stages of juvenile arthritis.

Adolescent↗
PubMed1991

C3 activation products, C3 containing immune complexes, the terminal complement complex and native C9 in patients with rheumatoid arthritis.

Complement activation products, C9 and C3-containing circulating immune complexes (CIC), were evaluated in plasma and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis. C3 activation products and the fluid phase terminal complement complex were considerably elevated in SF from RA patients reaching levels five- to eighttimes that in plasma, consistant with a local activation of the whole cascade in the joints. The results emphazise the importance of detecting C3 activation by neoepitope expression instead of single fragment determinations. The concentration of native C9 was lower in synovial fluid compared with plasma, consistant with the excessive local complement activation. Increased CIC levels which correlated with the degree of complement activation were also found in the SF from the RA patients.

Adult↗
PubMed1992

Immunohistological study of subretinal membranes in age-related macular degeneration.

An immunohistological study was performed on 6 specimens of subretinal membranes obtained surgically from patients suffering from age-related disciform macular degeneration. using immunoperoxidase procedures, we found in those membranes large amounts of IgG, IgA and IgE as well as C1q, C3c and C3d complement components diffusely distributed in the connective stroma and within the new blood vessel walls. Moreover, subretinal membranes contained numerous isolated HLA-DR- and -DQ-expressing cells, including glial, pigment epithelial and vascular endothelial cells. Monoclonal antibodies to immunocompetent cells disclosed only rare B and natural killer lymphocytes or suppressor-cytotoxic T cells, as well as some monocytes. These results show that immune phenomena are involved in proliferative changes associated with subretinal neovascularization. In addition, they suggest there are interactions between the immune system and peptide growth factors.

Antibodies, Monoclonal↗
PubMedDate not supplied

Analysis of polyethylene glycol precipitates from SLE sera: antibody enrichment in association with disease activity.

Twenty two systemic lupus erythematosus patients were assessed clinically for periods of up to six years. Polyethylene glycol precipitates of serial serum samples were analysed for the presence of autoantibodies by specific enzyme-linked immunoabsorbent assays. Increased enrichment of anti-Ro(SSA) was found to correlate with disease activity. Longitudinal studies of individual patients showed an association between disease exacerbation and enrichment of anti-Ro(SSA), anti-La(SSB) and anti-ssDNA. Circulating immune complexes isolated by anti-C3 affinity chromatography were also found to contain anti-Ro(SSA), anti-La(SSB) and anti-ss DNA and fixation of complement by complexes could be demonstrated. Enrichment of these autoantibodies in renal eluates of two patients with diffuse proliferative glomerulonephritis provided further evidence for a pathogenic role of these immune complexes.

Antigen-Antibody Complex↗
PubMed1991

[Value of the Coombs test in ABO incompatibility].

We studied the ABO haemolytic disease of the newborn in our neonatal unit to consider their serological aspects and clinical importance. 21% of all pregnancies were ABO incompatibles. The direct antiglobulin test was positive in 46 (11.3%) of them. The Elution was positive in all the newborns with direct antiglobulin test positive (Cd+). The anti-A o anti-B antibodies concentration in mothers was higher than 1/128 in 38 (84%). The C3d complement fraction was activated in two newborns. The infants Cd+ were born to group O mothers in all cases, and nobody was premature. Twelve (26%) of Cd+ presented jaundice which need phototherapy, and one moreover exchange transfusion. The direct antiglobulin test is very useful for detect the liable newborns of serious jaundice; therefore, we thing that is suitable to make this test in infants born to group O mothers. The newborns Cd+ did not have significant anemia at first three months of life.

ABO Blood-Group System↗
PubMed1990

[Recurrent post-infectious immune complex glomerulonephritis with persistent activation of the alternative complement pathway].

Recurring upper respiratory tract infections in a previously healthy 4 years old boy led to an acute nephritic syndrome requiring haemodialysis. Renal biopsy showed poststreptococcal like immune complex glomerulonephritis with subepithelial humps, C3 deposition and crescent formation. Renal function improved after methyl-prednisolone pulse therapy. Two relapses occurred in the following six months which responded to immunosuppressive therapy. 21 months following the first presentation the boy has normal glomerular filtration rate but persistent glomerular proteinuria and haematuria. Detailed complement analyses revealed a persistent activation of the alternate pathway.

Child, Preschool↗
PubMed1989

Paediatric coeliac disease and dermatitis herpetiformis: differences in complement activation in relation to diet.

We studied complement (C') involvement in paediatric coeliac disease (CD) and dermatitis herpetiformis (DH) in relation to lesions and function of enteric mucosa and to diet. For this purpose, 50 children affected by CD and 42 affected by DH were subdivided in 3 groups: in the first (I) were included subjects in free diet, in the second (II) children during gluten-free diet (GFD) and in the third (III) subjects after gluten reintroduction in diet. Only in CD we found significant modifications of some C' parameters. In fact C3 and C4 levels increase in II group in GFD (respectively p less than 0.02 and p less than 0.03) and result inversely correlated to an arbitrary score for the evaluation of the enteric histological lesions (p less than 0.02 and p less than 0.01). C3d/C3 ratio levels, as catabolic index of C3, result always greater than normal in both diseases, but significantly decrease only in II group of CD children (p less than 0.02), where they result also positively correlated to the histological score (p less than 0.05). Circulating immune complex-like material is higher in DH, but incidence of pathological values decrease in II group only in CD (p less than 0.04). These data suggest probable significant differences in the pathogenetic mechanisms of CD and DH involving C'.

Antigen-Antibody Complex↗