bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization and specificity of anti-endothelial cell membrane antibodies and their relationship to thrombosis in primary antiphospholipid syndrome (APS)
Authors: Hill M B , Phipps J L , Malia R G , Greaves M , Hughes P 
Published: July 2010

SUMMARYImmunoblotting was used to detect antibodies reacting with membrane and cytosol preparations of human umbilical vein endothelial cells (HUVEC), fibroblasts and a T lymphoma line HUT78 in 18 patients with anticardiolipin antibodies (ACA) (14 of whom had had a thrombotic event), 11 patients with a recent myocardial infarction and 17 controls. Multiple membrane-specific anti-bodies to HUVEC were found in 10 of the patients with ACA (28 bands) and in nine of the patients with thromboses (27 bands) in contrast to only three of the patients with myocardial infarction (four bands) and one control (one band). The most frequently recognized HUVEC membrane epitopes were at 33 kD (four sera), 61–63 kD (five sera) and 76–79 kD (four sera). Although cross-reactivity with fibroblast and/or HUT78 membranes was seen at 33 kD, binding at 61–63 kD and 76–79 kD was specific for endothelial membranes. Although no correlations with the presence and titre of ACA were seen, HUVEC membrane-specific antibodies showed a correlation with venous thrombotic events.
Peptide phage libraries can be an efficient tool for identifying antibody ligands for polyclonal antisera
Authors: Dybwad A , Bogen B , Natvig JB , FØRre Ø , Sioud M 
Published: July 2010

SUMMARYWe have examined the potential of isolating ligands for polyclonal antibodies from a nanopeptide phage library. The library was screened with a rabbit polyclonal antiserum raised against a synthetic peptide (ALWFRNHFVFGGGTKVT). Following screening, the positive phages were tested in an ELISA for their reactivity with the antiserum. Phages that showed positive reactivity with the antiserum compared with a normal rabbit serum were selected and their displayed peptides were determined. Among the 36 random positive clones, 31 clones carried the sequence AVFGGGTKL, PFFGGGSRA or APTGGSKRT that have a significant homology to the immunizing peptide. Five positive phages displayed the ATNIFIEGT sequence, which has no obvious linear homology with either the other selected peptides or with the peptide used for immunization. In contrast to the control peptide, the immunizing peptide inhibited binding of the antiserum to the peptide-displaying phages in a dose-dependent manner, thus demonstrating the specificity of the interaction. Furthermore, the rabbit B cell response to the peptide was found to be limited and focused on its C-terminal. Taken together, our data demonstrate the potential of random peptide phage libraries for defining epitopes for polyclonal antisera as well as for investigation of the nature of B cell responses to any given antigen.
Relationships between humoral factors in HIV-1-infected mothers and the occurrence of HIV infection in their infants
Authors: MABONDZO A , ROUVIER P , RAOUL H , LE NAOUR R , COURPOTIN C , HERVÉ F , PARNET-MATHIEU F , LASFARGUES G , DORMONT D 
Published: July 2010

SUMMARYBased on what is known about the biology of HIV-1 vertical transmission, the HIV burden of the mother, maternal immune factors and the integrity of the placental barrier are likely to play major roles. We therefore sought to determine whether the presence of antibodies in sera from 47 HI V-1- infected mothers, including 30 non-transmitting and 17 transmitting mothers, affected the risk of HIV-1 transmission to infants. Our findings showed no significant correlation between the capacity of antibodies to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) and their capacity to induce protection of the child from HIV-I infection (p=0.14). Furthermore, no correlation was found between the capacity of maternal antibodies to neutralize in vitro lymphocyte or macrophage heterologous viral infection and the occurrence of in vivo HIV-1 infection in the infant. Sera recovered from five of 12 transmitting mothers and from five of 11 non-transmitting mothers were compared in their capacity to neutralize the viruses drawn from the same individuals. Four out of five maternal isolates from transmitting mothers and all maternal isolates from non-transmitting mothers were sensitive to enhancement of infection mediated by the maternal serum.
High levels of the soluble form of CD30 molecule in rheumatoid arthritis (RA) are expression of CD30+ T cell involvement in the inflamed joints
Authors: Gerli R , Muscat C , Bistoni O , Falini B , Tomassini C , Agea E , Tognelllni R , Biagini P , Bertotto A 
Published: July 2010

SUMMARYThe CD30 is a surface molecule expressed by Th2-type lymphokine-producitig T cells upon activation. CD30-expressing activated T cells release a soluble form of the molecule, which can be detectable both in vitro and in vivo. In the present study, high levels of soluble CD30 were found in peripheral blood and synovial fluid from patients with RA. However, CD30+ CD3+ cells, either CD4+ or CD8+, were significantly present in synovial fluid, but not in peripheral blood, of RA patients. Serum values of soluble CD30 were higher in active than inactive RA patients and directly correlated with rheumatoid factor serum titres. These data strongly support an involvement of CD30+ T cells in the immune processes of rheumatoid synovitis, and may suggest a relationship between Th2-type cytokine-secreting T cells and the pathological response in RA.
Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL)
Authors: Marquart H V , GrØNbÆEk K , Christensen B E , Svehag S-E , Leslie R G Q 
Published: July 2010

SUMMARYIt has previously been reported that the expression of the complement receptors CRI (CD35) and CR2 (CD21) on malignant B cells in CLL is reduced compared with the expression on normal B cells, while deposition of complement C3 fragments, as a consequence of alternative pathway (AP) activation of complement, is observed on mononuclear cells from patients with B CLL. Following our demonstration that normal B cells are capable of activating the AP of complement in a CR2- dependent fashion, we have chosen to re-examine the complement-activating ability of B CLL cells in relation to their altered phenotype with respect to CR2 and the complement regulatory membrane proteins. CRI. Decay accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46). Flow cytometry was used to measure expression of complement receptors and regulatory proteins on CDS+ B cells from CLL patients, as well as the deposition of C3 fragments occurring both in vivo and after in vitro AP activation. We have confirmed the reduced expression of CRI and CR2 on CLL cells and have shown that AP activation in the presence of homologous, normal serum was reduced on B CLL cells compared with normal B cells. The degree of AP activation correlated directly with CR2 expression. In addition, we observed that CLL cells bear in vivo-deposited C3d, g, although at a significantly lower level than normal B cells.
Decreased release of IL-10 by monocytes from patients with lipoid nephrosis
Authors: Matsumoto K 
Published: July 2010

SUMMARYTL-10, a cross-regulatory cytokine produced by several cell types. Including monocytes, is known to stimulate B cell growth and maturation and to inhibit cytokine production, In order to characterize further monocyte function in patients with lipoid nephrosis (LN). the release of IL-10 was measured in supernatants of cultured peripheral blood monocytes (PBM) that were obtained from LN patients and healthy controls. Spontaneous and lipopolysaccharide (LPS)-induced IL-IO release was decreased in patients with LN compared with those in normal controls and lower in LN patients with the nephrotic syndrome (NS) than in those without NS. In contrast, the values in IgA nephropathy (IgAN) patients with or without NS did not differ from normal subjects. There was a negative correlation between IL-IO concentration and the quantity of vascular permeability factor (VPF) released in LN patients. These imply that there is a relative deficit in IL-10 release in active LN, which suggests the possibility that inadequate release of IL-IO may lead to increased VPF activity in active LN patients and the measurements of IL-10 may be of value for monitoring kidney disease. The data provide the first detailed analysis of IL-10 in a group of patients with LN.
The influence of tetracyclines on T cell activation
Authors: Kloppenburg M , Verweij C L , Miltenburg A M M , Verhoeven A J , Daha M R , Dijkmans B A C , Breedveld F C 
Published: July 2010

SUMMARYMinocycline has been shown to have an anti-inflammatory effect in patients with rheumatoid arthritis (RA). Since there is evidence that RA is a T cell-mediated disease, we investigated the effect of minocycline on human T cell clones derived from the synovium of an RA patient. The T cells, when activated via the T cell receptor (TCR)/CD3 complex, were suppressed functionally by minocycline, resulting in a dose-dependent inhibition of T cell proliferation and reduction in production of lL-2. interferon-gamma (IFN-γ) and tumour necrosis faetor-alpha (TNF-α). Besides an inhibition of IL-2 production, mitiocycline exerted its effect on T cell proliferation by induction of a decreased IL-2 responsiveness. We showed that the chelating capacity of minocycline plays a crucial role in the inhibitory effect on T cell function, since the inhibitory effect on T cell proliferation could be annulled by addition of exogenous Ca2+. However, minocycline did not markedly influence the typical TCR/CD3-induced intracellular Ca2+ mobilization. Taken together. the results clearly indicate that minocycline has immunomodulating effects on human T cells.
Efficacy of HIV-specific and ‘antibody-independent’ mechanisms for complement activation by HIV-infected cells
Authors: Saarloos M-N , Lint TF , Spear GT 
Published: July 2010

SUMMARYPrevious studies in this laboratory have shown that efficient activation of complement (C) on HIV isolates and HIV-infected cells requires the binding of specific anti-HIV antibodies, while other investigators have observed ‘antibody-independent’ C activation. In an attempt to clarify these disparate findings, we investigated the effect of several variables on C activation by HIV-infected cells using flow cytometric analysis of C3 deposition. Antibody-mediated C activation using pooled sera from infected persons or human MoAbs directed against the V3 region of gp120 was always substantially higher than activation without antibody. Normal human serum (NHS) from a subset of HIV antibody-negative donors did, however, induce low levels of C3 deposition. Differences in C3 activation between the various NHS did not correlate with total haemolytic C levels or mannose-binding protein (MBP) levels. IgM isolated from NHS that induced high levels of C activation was at least partly responsible for the ‘antibody-independent’ C activation. Although there appeared to be a correlation between NHS that induced C activation and the presence of anti-blood type B IgM, absorption of anti-B did not abrogate the C3 deposition. Additionally. MoAb to the B antigen did not induce C3 deposition. These studies show that IgM in sera from HIV-uninfected donors can induce C3 deposition on HIV-infected cells, but that specific antibody-dependent C activation is substantially more efficient. Therefore,‘antibody-independent’ C activation on HIV-infected cells may, in some cases, be more accurately described as HIV-cross-reactive antibody-dependent C activation.
A prospective study of CD45 isoform expression in haemophagocytic lymphohistiocytosis; an abnormal inherited immunophenotype in one family
Authors: Wagner R , Morgan G , Strobel S 
Published: July 2010

SUMMARY
In a prospective study, CD45 isoform expression on T lymphocytes was analysed in seven patients with haemophagocytic lymphohistiocytosis (HLH) and their family members. Six patients, their parents and seven healthy age-matched controls showed the normal pattern of three subpopulations of CD45R expression. In one patient, his mother and one of his healthy brothers only two subpopulations could be identified, which might indicate that the maturation from a CD45RA/RO double-positive to a CD45RO single-positive phenotype does not occur in these individuals. It is not clear if this finding had any impact on the development of HLH in this patient and if the pattern of CD45RA and RO expression observed in this family might represent a predisposition to HLH. In another patient a marked increase of the CD45RO single-positive T cell population was observed during a period of increased disease activity. The clinical relevance of this observation and whether CD45RO expression could serve as a marker for disease activity, or in selected individuals as a susceptibility marker for HLH, remain unknown.
Expression of MHC antigens by intestinal epithelial cells. Effect of transforming growth factor-beta 2 (TGF-β2)
Authors: Donnet-Hughes A , Schiffrin E J , Huggett A C 
Published: July 2010

SUMMARYThe effect of interferon-gamma (IFN-γ) and TGF-β2 on expression of MHC antigens by the human intestinal epithelial cell line HT-29 was examined by immunohistochemistry and flow cytometry. Untreated HT-29 cells constitutively expressed HLA-ABC but little HLA-DR. Expression of both molecules was increased by IFN-γ(100 U/ml, 24 h). TGF-β2 at concentrations × 0·5 ng/ml given before or simultaneously with IFN-γ, inhibited the IFN-induced expression of HLA-DR. Small increases in HLA-ABC expression by IFN-γ were further increased by pretreatment with TGF-β2, while a strong induction of HLA-ABC was inhibited by the TGF-β2 pretreatment. Our results suggest that the inhibitory action of the TGF-β2 on both HLA-ABC and HLA-DR correlates with the degree of induction following IFN-γ treatment. Since TGY-β2 is present in milk and is produced by gut epithelial cells, one of its possible functions may be to regulate expression of HLA antigens in the neonatal intestine and/or diseased intestine.
Up-regulated expression of Fas antigen (CD95) by peripheral naive and memory T cell subsets in patients with systemic lupus erythematosus (SLE): a possible mechanism for lymphopenia
Authors: Amasaki Y , Kobayashi S , Takeda T , Ogura N , Jodo S , Nakabayashi T , Tsutsumi A , Fujisaku A , Koike T 
Published: July 2010

SUMMARYFas antigen (CD95) is a membrane-associated molecule that mediates apoptotic cell death and may play a role in the induction and maintenance of T cell tolerance. To elucidate the involvement of Fas antigen in human autoimmune diseases, we analysed Fas antigen expression by peripheral T cells from patients with SLE and rheumatoid arthritis (RA), using three-colour flow cytometry. Both CD4+ and CD8+ T cell from SLE patients expressed Fas antigen in a higher density than did these cell from healthy donors and from RA patients. Enhancement of Fas antigen density was noted in Fas+CD45RO+ memory T cell from SLE patients. More remarkably, a significant expression of Fas antigen was observed in CD45RO− naive T cells from SLE patients CD4+CD45RO− T cells from SLE patients co-expressed Fas antigen and early to intermediate activation antigens such as CD25 and CD71, and late activation antigen HLA-DR in only FashiCD4+ naive T tells. Such up-regulation of Fas antigen expression in SLE patients seems to be clinically meaningful, because mean fluorescence intensity (MFI) of Fas antigen on CD4+ T cell subsets inversely correlates with the absolute size of CD4+ T tell subsets in peripheral blood of SLE patients. These results suggest that T cells with increased Fas antigen expression may be highly susceptible to apoptotic cell death, in vivo. A putative mechanism for lymphopenia in SLE patients is discussed.
The effect of free and liposome-encapsulated clodronate on the hepatic mononuclear phagocyte system in the rat
Authors: Camilleri J P , Williams A S , Amos N , Douglas-Jones A G , Love W G , Williams B D 
Published: July 2010

SUMMARYClodronate, encapsulated within small unilamellar vesicles (SUVc) will deplete hepatic macrophages after intravenous injection. Functional studies, using probes to evaluate hepatic Fc and C3b uptake, showed a close correlation between the inhibition of receptor-mediated uptake and the depletion of hepatic macrophages. Twenty milligrams of clodronate encapsulated within SUVc produced · 90% inhibition of uptake and clearance of Fc- and C3b-coated erythrocytes and a comparable reduction of hepatic macrophage numbers. Inhibition of macrophage receptor-mediated uptake of these erythroctyes was closely related to the reduction in macrophage numbers. Repopulation of macrophages within the liver took place over 2 weeks. At 1 week after depletion, although repopulation was taking place, receptor-mediated function remained suppressed. In a preliminary experiment, treatment of rats with adjuvant arthritis with 20 mg clodronate encapsulated in SUV suppressed the inflammation and reversed the course of the disease, while treatment with 20 mg free clodronate in saline or 20 mg clodronate in multilamellar vesicles (MLVc) did not.
Unaltered thyroid function in mice responding to a highly immunogenic thyrotropin receptor: implications for the establishment of a mouse model for Graves’ disease
Authors: Carayanniotis G , Huang G C , Nicholson L B , Scott T , Allain P , Mcgregor A M , Banga J P 
Published: July 2010

SUMMARYGrave's disease (GD) is a common disorder characterized by the presence of autoantibodies to the thyrotropin receptor. In the past, the exceedingly low expression of the thyrotropin receptor on thyrocytes has not allowed its purification in quantities sufficient to investigate the establishment of an animal model for this disease. In this study, we have purified the 398-amino acid, extracellular region of the human thyrotropin receptor (TSH-R.E) from insect cells using recombinant baculovirus, and explored its immunopathogenic properties in H-2b,d,q,k,s strains of mice. The receptor preparation was highly immunogenic since it elicited strong specific proliferative T cell responses as well as IgG responses in all strains tested. In addition, hyperimmunization with TSH-R.E induced (i) serum antibodies that blocked the binding of 125I-TSH to its receptor, a common feature of GD autoantibodies; and (ii) IgG that reacted with a synthetic peptide (residues 32–54) from the N-terminus of the receptor, a region implicated in the binding of thyroid stimulating antibodies. In SJL animals only, a weak antibody response to two other thyroid antigens, thyroglobulin and thyroid peroxidase, was also observed. The presence of these antibodies, however, was not accompanied by a detectable alteration in thyroid function as assessed by the measurement of serum TSH, T4 and iodine levels. Also mononuclear infiltration of the thyroid gland or morphological changes compatible with an activation state of thyrocytes were not apparent in TSH-R-challenged mice. In contrast, mice treated with the anti-oxidant aminotriazole showed a dramatic increase in serum TSH levels and an activated follicular epithelium. These data demonstrate that a highly immunogenic TSH-R.E in mice does not necessarily provide a proper stimulus for the induction of a hyper- or hypothyroid status as defined by hormonal or histological criteria. Main reasons for the inability to induce receptor-specific antibodies that affect thyroid function such as those generated in GD are likely to be the inappropriate folding of the recombinant extracellular domain of the receptor, or the xenogeneic nature of the autoantigen.
Expression of endogenous retroviruses, ERV3 and λ4–1, in synovial tissues from patients with rheumatoid arthritis
Authors: Takeuchi K , Katsumata K , Ikeda H , Minami M , Wakisaka A , Yoshiki T 
Published: July 2010

SUMMARYWe addressed the question of whether or not expression of human endogenous retroviruses (ERV). ERV3 and λ4–1, is related to the pathogenesis of rheumatoid arthritis (RA). In genomic Southern hybridization, there were no significant differences between RA patients and healthy volunteers with regard to frequencies of restriction fragment length polymorphism (RFLP) patterns, for either ERV3 or λ4–1. By Northern blot analysis using fresh synovial tissues, cultured synovial cells, and peripheral blood mononuclear cells (PBMC) from patients with RA, we noted two molecular species of ERV3 mRNAs of 3·5 kb and 9·0 kb sizes, and one single molecular species of λ4–1 mRNAs of 4·2 kb size. The expression was detected not only in RA patients but also in synovial cells from osteoarthritis (OA) as a non-RA control and PBMC from healthy volunteers, and was not related to RA activities or treatments. Although ERV3 and λ4–1 expression may not be directly associated with the pathogenic pathway of RA, the possibility exists that human ERV may have a causative role in autoimmune diseases, including RA. We also examined the effect of cytokines on the transcriptional regulation of ERV3. Although the level of ERV3 expression in cultured synovial cells did not change with IL-1β treatment, the level for cultured proximal tubular epithelial cells (hKEC) was up-regulated.
Synovial cells are potent antigen-presenting cells for superantigen, staphylococcal enterotoxin B (SEB)
Authors: Origuchi T , Eguchi K , Kawabe Y , Mizokami A , Ida H , Nagataki S 
Published: July 2010

SUMMARYThere is ample evidence suggesting that superantigens may act as a triggering factor in the pathogenesis of rheumatoid arthritis (RA). We investigated whether superantigen could activate T cells in the presence of synovial cells. T cells were cultured with SEB in the presence of interferongamma (IFN-γ)-treated synovial cells. T cell proliferation and activation were assessed by 3H-thymidine incorporation and IL-2 production. The expression of HLA class II antigens and adhesion molecules on synovial ceils was detected by flow cytometer. In the presence of IFN-γ-treated synovial cells, T cells proliferated vigorously and produced IL-2 in response to SEB. A low SEB-induced T cell response was noticed in the presence of untreated synovial cells. Allogeneic as well as autologous IFN-γ-treated synovial cells markedly enhanced SEB-induced T cell proliferation. IFN-γ-treated synovial cells had increased expression of HLA class II antigens and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules. MoAbs towards these antigens markedly inhibited the SEB-induced T cell response. These results indicate that activated synovial cells are potent antigen-presenting cells for SEB to T cells, and that superantigens may play a critical role in the pathogenesis of RA through activated synovial cells.