bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies to proteinase 3 increase adhesion of neutrophils to human endothelial cells
Authors: MAYET W-J , MEYER ZUM BÜSCHENFELDE K-H 
Published: July 2010

SUMMARYThe detection of anti-neutrophil cytoplasmic antibodies (ANCA), especially those with specificity for proteinase 3, is important in the diagnosis and in monitoring disease activity of Wegener's granulomatosis and related vasculitides. An ubiquitous feature of all ANCA-associated acute vascular injury is lytic necrosis. Adhesion of neutrophils to endothelium is a fundamental early step of the inflammatory response. Recently we were able to show that ANCA recognize their target antigen (proteinase 3) translocated into the membrane of human endothelial cells. The aim of this study was to investigate the effect of ANCA on the adhesion of neutrophils to human endothelial cells. Incubation of endothelial cells with affinity-purified antibodies to proteinase 3 (IgG- and F(ab′)2-fractions) led to a marked increase of neutrophil adhesion, with a peak after 4 h and a rapid decrease after 8 h. This effect could be inhibited by preincubation of the endothelial cells with an antibody to endothelial leucocyte adhesion molecule-1 (ELAM-1). Incubation with antibodies to proteinase 3 also led to an incrcase of endothelial ELAM-1 expression as measured in a cyto-ELISA and by flow cytometry. Our data demonstrate a direct effect of ANCA on neutrophil endothelial interactions. The enhanced adhesion of neutrophils occurs time-dependently via induction of ELAM-1 expression on the surface of endothelial cells. Our data give a hint of an ANCA-mediated mechanism of endothelial injury via induction of neutrophil adhesion to vascular endothelium in Wegener's granulomatosis and other ANCA-related vasculitides.
Glycation increases the vascular clearance rate of IgG in mice
Authors: KENNEDY D M , SKILLEN A W , SELF C H 
Published: July 2010

SUMMARY
As elevated levels of glycated IgG have been detected in the plasma of diabetics we have investigated whether glycation of IgG affects its vascular clearance rate, using a mouse model system. Polyclonal mouse IgG was aseptically incubated for 14–19 days with 0.5 m glucose in 0.1 m phosphate buffer (pH7.4) at 37 C, As control, IgG was incubated under identical conditions but with no added glucose. After incubation, both forms were labelled with 125I and injected intravenously into BALB/c mice. The rate of vascular clearance of the glycated IgG was found to be significantly higher than the control IgG in the periods 524 h (P&lt;0.001,n= 6) and 24–48 h (P&lt;0.01, n=6) after injection. After 2–3 days the mice were killed and the major organs were harvested. With glycated IgG there was a significant increase in the 125I accumulated in the kidney (P&lt;0.02). In later experiments, dual labelling with 131I and 1251 allowed mixtures of glycated and unglycated IgG to be injected into the same mouse so that the vascular clearance of both forms of IgG could be followed simultaneously. These experiments confirmed that glycation of the IgG significantly increases its vascular clearance rate.
Identification of human T cell epitopes in theMycobacterium lepraeheat shock protein 70-kD antigen
Authors: ADAMS E , BRITTON W J , MORGAN A , GOODSALL A L , BASTEN A 
Published: July 2010

SUMMARYIn a number of pathogens, heat shock proteins (hsp) stimulate humoral and cellular immune responses despite significant sequence identity with host hsp. The 70-kD hsp of Mycobacterium leprae, whieh shares 47% identity with human hsp70 at the protein level, elicited a T cell response in most Myco. bovis (bacille Calmette Guérin (BCG)) vaccinees as well as leprosy and tuberculosis patients and their contacts. In order to locate T cell epitopes, DNA fragments encoding portions of the 70-kD hsp were expressed in the vector pGEX-2T and tested for T cell reactivity in an in vitro proliferative assay. Cultures of peripheral blood mononuclear cells (PBMC) from BCG vaccinees indicated that the C-terminal half of the molecule contained multiple T cell epitopes, as the T cells from a majority of Myco. leprae hsp70-reactive individuals responded to C-344. Lower proportions of patients with paucibacillary leprosy (36%) and tuberculosis patients (16%) responded to C-344. The smaller C-142 fragment which includes the terminal 70 residues unique to Myco. leprae and is the target for the human antibody response elicited a cellular response in few patients and no vaccinees. In order to map T cell epitopes, two series of synthetic peptides encompassing the region 278–502 were prepared. Using overlapping 12mer and 20mer peptides, this region of the molecule was found to contain several potential T cell epitopes. The longer peptides gave a clearer indication of reactive sequences including regions of the molecule which were not identified with the 12mer peptides. Fine mapping of reactive peptide pools using the 12mer peptides identified two T cell epitopes. Although both were located in regions of the molecule shared with Myco. tuberculosis, one appeared to be cross-reactive with the equivalent human sequence, and thus has the potential to initiate autoimmune responses.
Anti-CD5 therapy decreases severity of established disease in collagen type II-induced arthritis in DBA/1 mice
Authors: PLATER-ZYBERK C , TAYLOR P C , BLAYLOCK M G , MAINI R N 
Published: July 2010

SUMMARYCollagen-induced arthritis has been widely used as an animal model of rheumatoid arthritis. We have used this model with a view to determining potential therapeutic targets for the treatment of human disease. To do this we have attempted to modulate the progression of established arthritis over a 10-day time period following the first appearance of disease, by i.p. injection of one of three different MoAbs. These consist of a rat IgG2a specific for the CD5 antigen expressed on all T cells and a subpopulation of B cells, a mouse IgG2b recognizing the CD72 antigen, and a rat IgM specific for the B220 molecule, CD72 and B220 both being expressed on all B cells. None of the three MoAbs had depleting activity in vivo. The progression of arthritis was monitored both clinically, and histologically. The effects of treatment with anti-CD5 and anti-CD72 antibodies were compared with control antibodies of the same species class and subclass. In the case of anti-B220 antibodies, the effects of treatment were compared with administration of FBS. Of these MoAbs, only treatment with anti-CD5 resulted in disease amelioration with significant decrease in disease severity in 60% of the animals. These changes became apparent 6 days after initiation of treatment. There were no significant differences in serum levels of IgG antibodies to native bovine collagen type II between the groups of treated and control mice. Possible mechanisms underlying the modification of disease expression following treatment with anti-CD5 MoAb are discussed.
Perforin expression by thyroid-infiltrating T cells in autoimmune thyroid disease
Authors: WU Z , PODACK E R , McKENZIE J M , OLSEN K J , ZAKARIJA M 
Published: July 2010

SUMMARYInfiltration of the thyroid gland by lymphocytes is a hall-mark of autoimmune thyroid disease; it is particularly evident in Hashimoto's thyroiditis but is also seen in most patients with Graves’ disease. Infiltrating cells are comprised primarily of T lymphocytes., of which only a minority appears to be activated. Their precise pathogenic role is largely unknown. Since perforin has been a marker for functionally activated cytotoxic T cells in situ we elected to assess the presence of perforin-containing cells in thyroid-infiltrating lymphocytes and establish their phenotype. Cells were isolated from seven subtotal thyroidectomy specimens, five from patients with Graves” disease and two with Hashimoto's thyroiditis. The novel findings were as follows: CD4+ perforin-containing T cells occurred only in Hashimoto's glands, suggesting a class II-restricted component of cytotoxicity; in Graves' disease, and to a lesser extent in Hashimoto's, perforin-expressing cells were primarily T cell receptor αβ+ CD4- CD8- (double negative); double negative perforin-containing cells in peripheral blood of normal individuals were largely γδ+T cells. In Hashimoto's samples, the predominant population of T cells expressing perforin was CD8+. By comparison, in studies of the synovial fluid of knee joints from patients with rheumatoid arthritis only a minor population of the perforin-containing cells was double-negative. The data suggest significant differences in cytotoxic autoimmune mechanisms between the two autoimmune thyroid diseases. Functional characterization of double-negative T cells is necessary to define their role in autoimmunity.
Characterization of neural cell adhesion molecule (NCAM) expression in thyroid follicular cells: Induction by cytokines and over expression in autoimmune glands
Authors: VARGAS F , TOLOSA F , SOSPEDRA M , CÁTALFAMO M , LUCAS-MARTÍN A , OBIOLS G , PUJOL-BORRELL R 
Published: July 2010

SUMMARYNCAM (CD56) is a cell surface glycoprotein of the immunoglobulin superfamily expressed on neuroendocrine and natural killer (NK) cells which has considerable molecular heterogeneity due to differential splicing and post-translational modifications. NCAM has been detected in the thyroid follicular cells (thyrocytes) immunohistological. We report here the molecular form, the modulation by cytokines and the levels of expression in thyroid pathology. By using a panel of MoAbs to NCAM on Western blots from thyrocyte extract we have determined that these cells express the 140- and 180-kD forms of NCAM, Exposure of primary cultures of thyrocytes to interferon-gamma (IFN-Γ), and even more, to the combination of IFN-Γ plus tumour necrosis factor-alpha (TNF-α) induced a clear increase in the expression of NCAM as assessed by FACS analysis. NCAM expression in thyrocytes was assessed by immunofluorescence in 59 surgical specimens of thyroid glands, and was found increased in 11/17 (64%) of Graves’, in 5/25 (20%) of multinodular goitre (MNG) and in occasional adenoma glands. No correlation was found with the expression of HLA class I. class II or the degree of lymphocytic infiltration scored in adjacent sections, but it was often seen in areas infiltrated by macrophages. In conclusion, NCAM is an adhesion molecule whose expression is clearly increased in thyrocytes in autoimmune glands, probably as a consequence of exposure to cytokines locally released. Since one of the forms of NCAM expressed by thyrocytes has the capability to generate intracellular signal it may play a role in normal thyroid function. In addition, NCAM may facilitate the recognition of thyrocytes by lymphocytes, particularly by NK CD56+ lymphocytes.
Failure in IgA secretion by surface IgA-positive B cells in common variable immunodeficiency (CVID)
Authors: SCOTT L J , BRYANT A , WEBSTER A D B , FARRANT J 
Published: July 2010

SUMMARY
CVID is an acquired disease with low serum immunoglobulins. Patients are classified into three groups on the ability of their B cells to secrete IgM and IgG in vitro in response to IL-2. We have now extended this patient classification to include IgA secretion and to assess whether the patients have IgA+ B cells in the circulation. B cells from almost all of the CVID patients studied were unable to secrete any IgA in vitro, with or without IL-2, although all B cells tested from normal donors showed some spontaneous IgA secretion. Thus, the defect with IgA secretion is more profound than with the secretion of IgM or IgG. Despite this failure to secrete IgA, using flow cytometry techniques all CVID patients tested were found to have IgA+ cells (expressed as a percentage of B cells) within the normal range. This suggests that CVID may involve a defect in the secretion of immunoglobulin isotypes rather than a defect in isotype switching.
Antineutrophil cytoplasm antibodies (ANCA) of IgA isotype in adult Henoch-Schönlein purpura
Authors: RONDA N , ESNAULT V L M , LAYWARD L , SEPE V , ALLEN A , FEHHALLY J , LOCKWOOD C M 
Published: July 2010

SUMMARY
ANCA are associated with certain forms of systemic vasculitis, and have been reported previously to be of the IgG and IgM isotype. We examined ihc possible association between IgA ANCA and the IgA-related diseases Henoch-Schönlein purpura (HSP) and IgA nephropathy (IgAN). IgA and IgG ANCA were detected by isotype-specific solid-phase assays with a crude neutrophil extract, and their presence was confirmed by antigen-specific fluid-phase competitive inhibition tests and by indirect immunofluorescence. The possible interference by IgA rheumatoid factor was excluded. IgA ANCA were detected in sera from 11/I4 HSP patients (79%). from 1/30 IgAN patients (3%), from 1/40 patients with vasculitides classically associated with IgG ANCA (2.5%), and in none or 60 sera from healthy blood donors. IgG ANCA were present with IgA ANCA in three patients with HSP. Only one HSP serum had anti-myeloperoxidase (MPO) activity by both IgA and IgG isotype-specific ELISA, and none was positive for proteinase 3 (PR3). Western blot analysis performed with neutrophil extract showed that the four strongest IgA ANCA-positive HSP sera reacted with a 51 -kD protein; Western blot performed on cellular fractions showed that this protein is primarily membrane-associated, and different from fibronectin. Our study suggests that adult HSP is closely associated with circulating IgA ANCA. which may be directed against a different autoantigen than that recognized by IgG ANCA.
Production and secretion of interferon-gamma (IFN-γ) in children with atopic dermatitis
Authors: TANG M , KEMP A 
Published: July 2010

SUMMARYIFN-γ is known to be a major inhibitor of IgE synthesis in vitro. Recent studies demonstrating reduced production of IFN-γ in children and adults with atopic dermatitis and elevated serum IgE suggest a similar role for this cytokine in vivo. The reasons for this reduced IFN-γ production are not known. One possibility is Ibal atopic individuals have a reduced population of cells producing IFN-γ in vivo. Using a fluorescence-labelled antibody to detect intracellular IFN-γ. the percentage of IFN-γ-producing cells was determined in children with atopic dermatitis and in non-atopic controls. Children with atopic dermatitis had a greater percentage of IFN-γ-producing ceils in unstimulated cultures compared with controls, indicating in vivo activation of lymphocytes in the atopic group. This could reflect the significant degree of inflammation present in these children, or the presence of bacterial infection or colonization. Although secretion of IFN-γ after stimulation with phorbol myristate acetate(PMA)/Ca was significantly lower in children with atopic dermatitis compared with controls, the percentage of IFN-γ-producing cells in the stimulated cultures from this group was equivalent to controls. This demonstrates that the reduced ability of atopic children to secrete IFN-γin vitro does not relate lo a lack of IFN-γ-producing cells, but to a difference in the regulation of IFN-γ production beyond the stage of signal transduction.
IgG glycosylation in autoimmune-prone strains of mice
Authors: BODMAN K B , HUTCHINGS P R , JEDDI P A , DELVES P J , ROOK G A W , SUMAR N , ROITT M , LYDYARD P M 
Published: July 2010

SUMMARYThe relationship between increased levels of IgG oligosaccharide chains lacking galactose (G0) and the development of rheumatoid arthritis is unclear. In order to further our understanding of the observed correlation between raised serum G0 and arthritis, we have studied G0 levels in arthritis prone and non-susceptible (i.e., non-arthritis-prone) mice and the effects on G0 of mycobacterial antigens, which have been postulated to play a role in the early events leading to the development of arthritis. We have shown that different age-matched mouse strains have characteristic “resting” levels of G0 which (in six out of seven strains of mice) increase with age. We have also shown that these increases can be enhanced by immunization of arthritis-prone strains of mice with an adjuvant containing mycobacteria (Freund's complete adjuvant (FCA)), suggesting that deflects in the ability to regulate these G0 changes may be related to susceptibility to arthritis.
The effect of anti-CD4 on helper function of CD4,45RA+ versus CD4,45RO+ T cells
Authors: WANG J , YAN T , SIMMER B , EMMRICH F 
Published: July 2010

SUMMARYHere we have investigated and compared the effects oranti-CD4 on helper function of CD4, 45RA+ versus CD4, 45RO+ Tcells. Only CD4, 45RO+ cells, but not CD4, 45RA+ cells were able lo promote B cell differentiation resulting in immunoglobulin production in vitro(IgM as well as IgG) which could be inhibited by anti-CD4 MoAbs (MAX.16H5 and T151). In pokeweed mitogen (PWM)-induced B cell proliferation a similar pattern of responsiveness was obtained. When we studied the anti-CD4 effects on cytokine production in T cells stimulated in mixed lymphocyte reaction (MLR) or by mitogens, we found that neither IL-2 nor IL-4 production was dramatically influenced by anti-CD4 in CD4, 45RO+ cells. This led us to the conclusion that the inhibitory effect olanti-CD4 on B cell proliferation and immunoglobulin secretion was not due lo inhibition of cytokine production. To clarify this point, we investigated the ability of anti-CD4 to inhibit conjugate formation between B and T cells. It was found that CD4, 45RO+ T cells formed more conjugates than CD4, 45RA+ cells, and that only the conjugate formation by CD4, 45RO+ T cells was inhibited by anti-CD4. These results suggest that (i) anti-CD4 inhibits T helper functions primarily by affecting CD4, 45RO+ cells, and (ii) this effect is probably mediated by contact inhibition in the early phase of T-B collaboration.
Circulating autoantibodies directed against conjugated fatty acids in sera of HIV-1-infected patients
Authors: AMARA A , CHAUGIER C , RAGNAUD J-M , GEFFARD M 
Published: July 2010

SUMMARYSeveral reports have demonstrated that major changes occur in the fatty acid content of HIV-infected cells. In order to evaluate if these changes are recognized by the immune system, we have attempted to assay the possible presence of autoantibodies (autoAb) directed against conjugated fatty acids (CFA). Using an adapted ELISA, anti-CFA autoAb were assayed in sera of 150 HIV-1- infected patients and 116 controls (healthy donors and patients suffering from other diseases). Significantly increased anti-CFA autoAb of IgG class were found in HIV-1-infected patients (α &lt; 0 001). Using our ELISA method and CFA differing in their length and their degree of unsaturation (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoienic, linolcic, ligniceric, araehidonic, eicosapentaenoic and docosabexaenoic acids), it was demonstrated that the acyl chain of CFA is the immunodominanl part recognized by these autoAb. Anti-CFA autoAb were present in 15/52 asymptomatic carriers, 14/36 symptomatic carriers, 16/39 ARC patients, but only 3/23 AIDS patients. Anti-CFA aetivity seemed to be linked with the CD4+ T cell count, and was not related to the total IgG amounts. Anti-CFA autoAb could result from self-antigen presentation to immunological cells, and may reflect lipid membrane modifications occurring in HIV-infected cells.
The significance of anti-streptokinase antibodies
Authors: LYNCH M , PENTECOST B L , LITTLER W A , STOCKLEY R A 
Published: July 2010

SUMMARY
Antibodies to streptokinase (SK) are widespread in the population, but reports of their effect on the action of SK are conflicting. Specific anti-SK IgG was purified from the sera of 10 patients, five with low titres of anti-SK IgG and five with high titres. The effect of increasing specific anti-SK IgG antibodies on the action of SK was evaluated IN vitro using a fluorimetric assay for plasmin and by a fibrin plate lysis assay. The inhibition of SK by whole plasma from a further group of patients was also assessed by the fibrin plate assay. There was a positive correlation between the serum antibody concentration and the quantity of specific anti-SK eluted (r= 0.797;P&lt;0.005). The addition of specific anti-SK IgG caused a dose-related decrease in SK activity (fluorimetric assay r =−0.93; P = 0.02; fibrin plate assay r =−0.98: P&lt;0.001). The addition of patient plasma to the fibrin plate assay also resulted in decreased lysis, which was dependent upon antibody titre (r=−0.95; P&lt;0.0001). Significant in vitro reduction of the activity of SK by specific antibody was demonstrated, and this was similar with plasma containing comparable amounts of antibody. The findings suggest that treatment with SK would be unlikely to induce an effective thrombolytic slate when antibody titres are high (such as those seen within 2 years of an initial dose of SK).
IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease
Authors: MITSUYAMA K , TOYONAGA A , SASAKI E , WATANABE K , TATEISHI H , NISHIYAMA T , SAIKI T , IKEDA H , TSURUTA O , TANIKAWA K 
Published: July 2010

SUMMARYIL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC),18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found lo contain significantly more IL-8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P&lt;0.001: CD, P&lt;0.001), in patients with other types of colitis (UC, P&lt;0.05; CD, P&lt;0.01), or in normal control subjects (UC. P&lt;0.001; CD. P&lt;0.001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P&lt; 0.001). Colonic lL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0.950, P&lt;0.001; CD. r=0-940, P&lt;0.001), and with colonic IL-1β (r=0.911, P&lt;0.001) and tumour necrosis factor-alpha (TNF-a) levels (r=0-604. P &lt; 0001) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-I and TNF-a in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease.
Effects of ethanol consumption and withdrawal on B cell subpopulations in murine bone marrow
Authors: KRUGER T E , JERRELLS T R 
Published: July 2010

SUMMARYWe designed studies to examine the effects of ethanol consumption and withdrawal on the numbers of pre-B and B cells in murine bone marrow. Flow cytometric analysis of B220 and surface IgM expression on bone marrow cells revealed that consumption of ethanol by mice for 7 days led to a significant reduction in pre-B cells. The number of mature B cells in the bone marrow of these animals, however, did not differ from that of control mice. In contrast, examination of bone marrow obtained from mice at various times after withdrawal from ethanol showed significantly fewer numbers of mature B cells and an even greater toss of pre-B cells. This effect was seen for relatively long periods after withdrawal. These study findings are interpreted to suggest that ethanol consumption results in changes in the pre-B cell population in murine bone marrow, II also appears that withdrawal from ethanol results in more profound changes in the mature B cell population of the bone marrow than those that occur during ethanol consumption.