bluuebunny/crossref_metadata_2025_split huggingface dataset:
FcγRIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease
Authors: Botto M , Theodoridis E , Thompson E M , Beynon H L C , Briggs D , Isenberg D A , Walport M J , Davies K A 
Published: November 2003

SUMMARY
An allotypic variant of FcγRIIa, FcγRIIa-HR (FcγRIIa-R131), has been shown in vitro to reduce the capacity of phagocytic cells to bind and internalize IgG-containing immune complexes. Our aim was to determine whether this allotypic variant was associated with susceptibility to SLE and the development of lupus nephritis, as previous studies have suggested. FcγRIIA genotype analysis was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 215 Caucasoid, 70 Afro-Caribbean, and 46 Chinese patients with SLE, and in 259, 77, and 49 ethnically matched controls, respectively. Distribution of FcγRIIa genotypes between the patients and ethnically matched controls was not significantly different in the three populations studied. No association between the FcγRIIa-HR allotype and nephritis was found. Our results suggest that the FcγRIIa-HR allotype is not a major factor predisposing to the development of SLE, or to lupus nephritis.
Production of nitrite by dengue virus-induced cytotoxic factor
Authors: Misra A , Mukerjee RUMA , Chaturvedi U C 
Published: November 2003

SUMMARY
Dengue type 2 virus (DV) infection induces production of a cytokine, the cytotoxic factor (CF) in the spleen of mice. The present study was undertaken to investigate the production of nitrite (NO−2) by the spleen cells of mice in vitro and in vivo following inoculation of DV or CF. Maximum NO−2 production occurred at 45 min after inoculation of 5 μg CF, both in vitro and in vivo. The NO−2 was produced by macrophages and T cells and not by B cells. Pretreatment of CF with anti-CF antisera inhibited production of NO−2. DV-stimulated spleen cell culture supernatants showed peak production of CF and NO−2 at 72 h. In DV-infected mouse spleen, maximum NO−2 production occurred at 8–11 days post-infection, which correlated with peak cytotoxic activity in the spleen. Pretreatment of spleen cells with NG-monomethyl l-arginine (NMMA) inhibited NO−2 production. NO−2 production was abrogated in a dose-dependent manner by treatment of spleen cells with Ca2+ channel blocking drug, Nifedipine. The findings demonstrate that DV-induced CF induces production of NO−2 in spleen cells, probably in a Ca2+-dependent manner, and may be a mechanism of target cell killing.
Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid arthritis (RA)
Authors: Hoffmann J C , Bayer B , Zeidler H 
Published: November 2003

SUMMARY
Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS–PAGE, and Western blotting. Gel filtration gave similar peaks at 95–125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2+ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation.
VH gene-family representation in peripheral activated B cells from systemic lupus erythematosus (SLE) patients
Authors: Demaison C , David D , Fautrel B , Theze J 
Published: November 2003

SUMMARY
A semiquantitative polymerase chain reaction (PCR) assay described in this study has been used to analyse the VH1, VH3 and VH4 repertoire expressed by total IgM+ and IgG+ B cells from normal individuals and lupus patients. This approach consists of a combination of B cell selection, utilization of the anchored PCR technique to avoid technical bias in the amplification of different VH gene family cDNA templates, and screening of the amplified IgM or IgG cDNA rearrangements by family-specific oligonucleotide probes. In four lupus patients, VH family representation in IgM+ and IgG+in vivo activated B cells, selected by anti-CD71 antibody, and in total CD19+ B cells were compared. In all patients, VH4 gene family segments were preferentially underrepresented in IgM+ activated B cells. In IgG+ B cells the results suggest that VH4 expression is variable, depending on the phase of the disease. Polyclonal B cell activation, which is usually considered as being the first event in autoantibody production in SLE, cannot explain our results. The data evoke the possible involvement of a VH4-specific B cell superantigen in the onset or development of SLE. This hypothesis is also supported by the sequence conservation of the fourth β loop—a putative superantigen binding site—of functional VH4 gene segments which are preferentially used by anti-dsDNA lupus antibodies of established clones and hybridomas.
Function of C3 in a humoral response: iC3b/C3dg bound to an immune complex generated with natural antibody and a primary antigen promotes antigen uptake and the expression of co-stimulatory molecules by all B cells, but only stimulates immunoglobulin synthesis by antigen-specific B cells
Authors: Thornton B P , Větvička V , Ross G D 
Published: November 2003

SUMMARY
Previous studies have shown that an optimal humoral response to a primary protein antigen requires C3 and CR2 (CD21). Sera from non-immunized donors contain natural IgM and IgG antibodies to the primary antigen keyhole limpet haemocyanin (KLH), and these have been previously shown to form immune complexes (IC) that activate the classical pathway of C, fixing iC3b/C3dg onto the KLH antigen. Such KLH IC bind to CR2 on KLH-non-specific B lymphocytes, resulting in antigen processing and MHC class II-dependent presentation to KLH-specific helper T cells. KLH IC also induce B lymphocytes to express the CD80 co-stimulatory molecule via simultaneous CR2 ligation with C3 and FcγRII (CD32) stimulation by IgG natural antibody. The current study demonstrated that KLH IC ligation to either CR2 or FcγRII resulted in activation of a second co-stimulatory molecule, LFA-1 (CD11a, CD18). The possibility of polyclonal B cell stimulation by the presentation of KLH-iC3b/C3dg by antigen-non-specific B cells was excluded by demonstration that in vitro cultivation of peripheral blood mononuclear cells (PBMC) with KLH-iC3b/C3dg elicited only anti-KLH, and did not stimulate synthesis of antibodies to hepatitis C virus (HCV) or tetanus toxoid (TT). Of greatest significance, a specific anti-KLH response was only detectable in cultures stimulated with KLH-iC3b/C3dg and not in cultures stimulated with KLH alone or KLH-IgG. Thus, iC3b/C3dg that was bound to a primary protein antigen enhanced recognition and specific immunoglobulin synthesis by antigen-specific B cells, even though the antigen was taken up and processed via CR2 by both antigen-specific and non-specific B cells.
Dietary β-carotene and ultraviolet-induced immunosuppression
Authors: Noonan F P , Webber L J , de Fabo E C , Hoffman H A , Bendich A , Mathews-Roth M 
Published: November 2003

SUMMARY
Ultraviolet (UV)-induced immunosuppression is a critical step in UV carcinogenesis, permitting tumour outgrowth. We investigated the effect of dietary β-carotene on UV suppression of contact hypersensitivity (CHS) to trinitrochlorobenzene (TNCB) in BALB/c mice. Mice were fed for 10–16 weeks chow alone or supplemented with 1% β-carotene or placebo as beadlets. Serum β-carotene was detectable by high performance liquid chromatography (HPLC) analysis only in β-carotene-fed mice (2.06 ± 0.15 μg/ml). Serum retinol was 0.22–0.27 μg/ml in all three groups. Mice (n = 41/dietary group) were irradiated with 0, 4.5, 9 or 18 kJ/m2 of UVB and the CHS response was measured. Decreased CHS responses were observed in all UV-irradiated groups compared with unirradiated controls. UV dose–responses for suppression of CHS derived by first-order regression analyses of plots of percentage suppression of CHS as a function of log10UV dose showed significant slopes (P &lt; 0.02) for all three dietary groups and similar residual variances between groups, P &gt; 0.05. The UV dose for 50% suppression of CHS was 6.3 kJ/m2 for control, 6.4 kJ/m2 for placebo, and 5.5 kJ/m2 for β-carotene-fed mice. No significant differences in slopes or elevations between UV dose–responses were observed, P &gt; 0.05. Skin levels of the initiator of UV-induced immunosuppression, cis urocanic acid, were determined by HPLC in mice given 0 or 9 kJ/m2 of UV (n = 28/dietary group). No significant differences were observed between dietary groups (range 35.2–41.1 ng/mg skin, P &gt; 0.15) We conclude feeding β-carotene to BALB/c mice does not alter susceptibility to UV immune suppression, in contrast to human studies.
Generalized immune activation in pulmonary tuberculosis: co-activation with HIV infection
Authors: Vanham G , Edmonds K , Qing L , Hom D , Toossi Z , Jones B , Daley C L , Huebner R , Kestens L , Gigase P , Ellner J J 
Published: November 2003

SUMMARY
Parameters of immune activation/differentiation were studied in a group of newly diagnosed HIV− and HIV+ pulmonary tuberculosis (TB) patients. Compared with controls, HLA-DR expression on both CD4 and CD8 T cells from the HIV− TB patients was approximately doubled; HLA-DR on T cells from the HIV+ group was tripled. The monocytes from both groups of patients expressed abnormally high levels of the Fcγ receptors I and III. Serum levels of tumour necrosis factor-alpha (TNF-α), neopterin and β2-microglobulin were increased in HIV− and even more so in HIV+ TB patients. The expression of HLA-DR on T cell subsets and of FcγR on monocytes correlated with each other, but not with serum activation markers. This pattern of non-specific activation during TB infection may be associated with enhanced susceptibility to HIV infection.
Cross-reactive antibodies between HIV-gp120 and platelet gpIIIa (CD61) in HIV-related immune thrombocytopenic purpura
Authors: Bettaieb A , Oksenhendler E , Duedari N , Bierling P 
Published: November 2003

SUMMARY
We have previously demonstrated that immune platelet destruction observed in an AIDS-free HIV-infected patient was associated with the presence of a cross-reactive antibody recognizing both HIV-glycoprotein (gp)120 and platelet gpIIIa (CD61). We have now investigated the presence of such antibodies in other HIV-infected patients, together with the molecular structure of the cross-reactive epitope. Platelet gpIIb/IIIa antibodies were characterized in sera from HIV-infected patients with immune thrombocytopenic purpura by means of an ELISA and a radioimmunoprecipitation procedure (RIP). The platelet antibodies were purified and tested for their ability to recognize HIV-gp. We also tried to characterize the antibody target epitope on HIV-gp120 using recombinant gp and synthetic peptides. IgG with anti-gpIIb/IIIa activity were detected, by means of an ELISA with purified gpIIb/IIIa, in 101/138 (73%) sera from HIV-infected patients with immune thrombocytopenic purpura. The platelet antibodies were purified from 23 sera by absorption/elution on purified immobilized platelet gpIIb/IIIa, and recognition of gpIIIa was confirmed in eight cases with a RIP. Furthermore, the presence of a cross-reactive antibody between HIV-gp120 and platelet gpIIIa was demonstrated in 18/18 patients (including the eight with a confirmed gpIIIa antibody) by the ability of the serum HIV-gp160/120 antibodies to bind to purified gpIIb/IIIa. The cross-reactive epitope was shown to be independent of the carbohydrate moieties of gp120, since deglycosylation of two recombinant (r)-gp120s did not abolish antibody binding. However, the antibody did not recognize synthetic gp120 peptides spanning 355 of the 516 amino acids of gp120, particularly the four regions exhibiting sequences of four or five consecutive amino acids that are identical between r-gp120 and gpIIIa. Our results thus support the hypothesis that the cross-reactive antibody recognizes the conformational structure of gp120. These results strongly suggest that molecular mimicry between HIV-gp120 and platelet gpIIIa may be important in the pathogenesis of immune thrombocytopenia in AIDS-free HIV-infected patients.
Differential maturation of avidity of IgG antibodies to gp41, p24 and p17 following infection with HIV-1
Authors: Thomas H I J , Wilson S , O’Toole C M , Lister C M , Saeed A M , Watkins R P F , Morgan-Capner P 
Published: November 2003

SUMMARY
We have evaluated solid-phase ELISA IgG antibody avidity studies as a means of identifying cases of recent HIV-1 infection. Although separate studies on the avidity of anti-gp41 and anti-p24 antibodies in seroconvertors have been reported, a comparison of the ability of patients to simultaneously mature their immune response to more than one HIV antigen immediately following seroconversion appears to be lacking. We have demonstrated a maturation in anti-gp41 avidity which reflects the time since seroconversion in all cases. In contrast, however, only some patients produced high-avidity anti-p24 or anti-p17 antibodies during the same time span. While the avidity of anti-gp41 antibodies remained high in cases of non-recent HIV infection, even in the face of advanced disease, we have confirmed the findings of others that the avidity of anti-p24 falls before the onset of ARC or AIDS. Therefore, whilst the avidity of anti-gp41 antibodies could reliably be of value in identifying cases of recent HIV infection, the avidity of anti-p24 or anti-p17 antibodies could not, but may be of prognostic value, even at an early stage. The time taken to reach maximum anti-p17, anti-p24 and anti-gp41 titres was variable, but anti-gp41 titres, like anti-gp41 avidity, remained high. In contrast, anti-p24 titres fell, even during the early follow-up period in some seroconvertors. Anti-p24 antibody avidity, however, appeared to be a better predictor of disease progression in ‘remote’ cases than anti-p24 titre. The avidity and titres of these antibodies are presented in relation to the clinical details, p24 antigen status, CD4 and CD8 counts where these are known.
Virus-specific cytotoxic T cell responses are associated with immunity of the cottontop tamarin to Epstein–Barr virus (EBV)
Authors: Wilson A D , Shooshstari M , Finerty S , Watkins P , Morgan A J 
Published: November 2003

SUMMARY
The cytotoxic responses of peripheral blood lymphocytes from cottontop tamarins to in vitro re-stimulation with autologous lymphoblastoid cell lines (LCL) were assayed. Lymphocytes from immune tamarins that had recovered from EBV challenge developed potent cytotoxicity for natural killer (NK) cell targets and for autologous LCL. The cytotoxicity for LCL targets was EBV-specific, as B cell blasts uninfected with EBV were not killed. The cell lines could be maintained by repeated stimulation with LCL and the addition of IL-2. Flow cytometry showed that they were T cell lines expressing CD2, CD3, CD4, CD8 and CD25. Dual-colour flow cytometry revealed two subpopulations, one CD4+ CD8+ population and the other CD4− CD8+. After separation by magnetic cell sorting both subpopulations were shown to be cytotoxic and the CD4+ CD8+ fraction was also shown to be MHC class II-restricted; the MHC restriction of the CD8+ subpopulation could not be determined. The unseparated T cells and both the subpopulations were able to inhibit LCL outgrowth in vitro. In contrast, PBL from naive tamarins stimulated by autologous LCL developed less NK cell cytotoxicity and little cytotoxicity for LCL. The cytotoxic response was enhanced at higher levels of LCL stimulation, but the cells were unable to inhibit LCL outgrowth in vitro. We conclude that cytotoxic responses capable of inhibiting LCL growth in vitro correlate with in vivo immunity in the tamarin model and provide a basis for understanding the mechanism of vaccine-induced immune protection.
Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls
Authors: Nilsen E M , Gjertsen H A , Jensen K , Brandtzaeg P , Lundin K E A 
Published: November 2003

SUMMARY
Coeliac disease is apparently a T cell-mediated disease, precipitated in the proximal small intestine of susceptible individuals by gluten. Preferential presentation of gluten peptides most probably takes place in coeliac mucosa by the disease-associated HLA-DQ2 and -DQ8 molecules. In peripheral blood, however, both HLA-DR, -DQ and -DP-restricted T cell responses to gluten have been observed. We examined gluten-specific T cell clones (TCC) derived from peripheral blood for cytokine production to see if their profiles were related to the HLA restriction or the disease state of the donors. As previously found for mucosal TCC, the main product was interferon-gamma (IFN-γ), often with additional IL-4, IL-5, IL-6, IL-10, tumour necrosis factor, and transforming growth factor-beta. Regardless of restriction element or disease state, gluten-reactive TCC from peripheral blood therefore seem to secrete cytokines compatible with a Th0 profile.
IL-6-induced anaemia in rats: possible pathogenetic implications for anaemia observed in chronic inflammations
Authors: Jongen-Lavrencic M , Peeters H R M , Rozemuller H , Rombouts W J C , Martens A C M , Vreugdenhil G , Pillay M , Cox P H , Bijser M , Brutel G , Breedveld F C , Swaak A J G 
Published: November 2003

SUMMARY
Anaemia of chronic disease (ACD) is frequently found in rheumatoid arthritis (RA). In the pathogenesis of ACD both cytokines, such as tumour necrosis factor-alpha (TNF-α), IL-1 and Il-6 as well as a relative deficiency of erythroprotein (EPO), are thought to play a key role. In the present study the role of IL-6 in the pathogenesis of this anaemia was investigated. IL-6 was administered intraperitoneally to rats for 14 sequential days. It appeared that IL-6 was able to induce anaemia. No evidence for suppression of bone marrow erythropoiesis or enhanced sequestration of erythrocytes in the liver was found. However, decreased plasma and bone marrow iron contents were observed in anaemic rats. Blood loss in intestinal tissue was demonstrated using erythrocyte labelling with 99mtechnetium. Histologically this was associated with inflammatory cell infiltration, oedema and bleeding in the intestinal wall. In conclusion, IL-6 induced anaemia in rats. This anaemia was caused by intestinal blood loss.
T cell clones from a Sjögren’s syndrome salivary gland biopsy produce high levels of IL-10
Authors: Brookes S M , Cohen S B A , Price E J , Webb L M C , Feldmann M , Maini R N , Venables P J W 
Published: November 2003

SUMMARY
Sjögren’s syndrome (SS) is characterized by a focal periductal salivary gland infiltrate consisting mainly of T and B lymphocytes. Most of the T cells bear the memory of CD4+ Th-1-like phenotype and express high levels of class II, though CD8+ cells are also present. We have studied 17 labial salivary gland and 15 peripheral blood T cell clones from a patient with primary SS. The tissue clones were 71% CD8+ and 29% CD4+, and the peripheral blood-derived clones were 60% CD8+ and 40% CD4+. The CD4+ T cell clones from both the salivary gland and autologous peripheral blood were of the Th1 phenotype, in that they produced interferon-gamma (IFN-γ) and IL-2 but very little IL-4 after 24 h stimulation with phorbol myristate acetate and anti-CD3 antibody. The salivary gland-derived CD4+ clones produced 15 times more IL-10 (7.92 ng/ml) than peripheral blood-derived CD4+ clones (0.52 ng/ml, P≤0.02). The tissue CD8+ clones produced 1.2 times (P&lt;0.04) more IFN-γ and CD4+ clones produced 3.5 times less IL-2 (P&lt;0.02) than the respective PBM-derived clones. The accumulation of Th1-type cells producing high levels of IL-10 in the salivary gland suggests a specific immunoregulatory function at the site of inflammation in SS.
Impairment of the inhibitory effect of sodium on basophil histamine release in patients with systemic sclerosis
Authors: Tedeschi A , Palella M , Milazzo N , Mascagni B , Miadonna A 
Published: November 2003

SUMMARY
It has been demonstrated that Na+ down-regulates IgE-dependent and IgE-independent histamine release from basophils of normal subjects. The aim of this study was to evaluate whether Na+ exerts its inhibitory effect on basophil histamine release in patients with systemic sclerosis (SSc). Peripheral blood leucocytes were stimulated with anti-IgE, n-formyl-methionyl-leucyl-phenylalanine (fMLP) and IL-3 in the presence of high and low Na+ concentrations, and histamine release was measured by a fluorometric method. The dose–response curves of histamine release induced by the above stimuli were similar in SSc patients (n = 15) and in normal subjects (n = 39). Na+ removal from the extracellular medium and its isosmotic replacement with choline chloride led to a significant increase of anti-IgE-and fMLP-induced histamine release in normal subjects, but not in SSc patients. In the former population, histamine release induced by an optimal dose of anti-IgE (1/5000) was 26.4 ± 3.1% in high Na+ and 59.3 ± 3.5% in low Na+ (mean ± s.e.m., P &lt; 0.0001), whereas in the latter population mean histamine release was 20.4 ± 5.1% in high Na+ and 15.8 ± 2.9% in low Na+ (P NS). A similar trend was observed when basophils were stimulated with fMLP. Na+ exerted a dose-dependent inhibitory effect on anti-IgE- and fMLP-induced histamine release in normal subjects, but not in SSc patients. IL-3-induced histamine release from basophils of SSc patients was increased in a low-Na+ solution, but to a lesser extent when compared with normal controls. Therefore basophils from normal subjects and SSc patients behave in a different way when stimulated in a low-Na+ medium. The inhibitory effect of Na+ on basophil histamine release is impaired in SSc patients, and this abnormality could contribute to basophil dysfunction.
Role of glycosaminoglycans (GAGs) in regulation of the immunogenicity of human vascular endothelial cells
Authors: Rix D A , Douglas M S , Talbot D , Dark J H , Kirby J A 
Published: November 2003

SUMMARY
Heparan sulphate is a common glycosaminoglycan component of proteoglycans present on the luminal surface of vascular endothelium. It has been proposed that an important function of these molecules is the sequestration of a range of proinflammatory and proadhesive cytokines. Such cytokines play a vital role during lymphocyte recruitment from the blood at sites of inflammation. In this study it is shown that the effects of interferon-gamma (IFN-γ), but not of tumour necrosis factor-alpha (TNF-α), are inhibited by treatment with soluble heparin. Specifically, heparin was shown to inhibit the induction of class II MHC antigens and the up-regulation of intercellular adhesion molecule-1 (ICAM-1) produced by treatment of cultured human endothelial cells with IFN-γ. Furthermore, it was shown that heparin blocked the enhanced adhesion of T lymphocytes to IFN-γ-treated endothelial cells. Investigation of the inhibitory effects of other GAG molecules demonstrated a requirement for heparin-like structural domains as chondroitin sulphate was unable to inhibit the function of IFN-γ. These results may explain reported immunosuppressive properties of heparin, and are consistent with the model that heparin may compete with cell surface GAGs to bind IFN-γ, thereby reducing effective biological activity.