bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigenic structure of the hepatitis C virus envelope 2 protein
Authors: ZHANG Z-X , SÖNNERBORG A , SÄLLBERG M 
Published: July 2010

SUMMARY
The antigenic structure of the envelope 2 (e2) protein of the hepatitis C virus (HCV) was characterized by the use of 70 synthetic peptides and 131 human sera from persons with antibodies to HCV, Among 34 overlapping peptides spanning the e2 protein of HCV, two major antigenic regions were located to residues 484–499 and residues 554–569. The sequence of the two major antigenic regions of the e2 protein are partly well conserved within the described types of HCV. Both regions contain two Cys residues in close proximity, and the region at residues 554–569 contains a putative N-glycosylation site, which are factors that previously have been suggested to affect the immune recognition of the e2 protein. Using substitution peptide analogues where each position within residues 484–499 and 554–569 were sequentially substituted by Ala or Gly, the most essential residues for antibody binding were found to be the Pro-498, Ala-499, Ala-566, Pro-567, and Pro-568. All of these, except for the Pro-498 and Ala-566, are conserved among different HCV strains. Also, according to previous studies, position 496 often shows variations, which could be explained by position 496 being contained within the antigenic region at residues 484–499. Interestingly, none of the Cys residues at positions 486, 494, 564 and 569 were found to be essential for antibody binding, indicating that these are not essential in maintaining the e2antigenicity of the peptides. In a material of 114 confirmed anti-HCV positive sera, derived from patients during the acute or the chronic phase of HCV infection, the prevalence of antibodies to the two major linear antigenic regions of the e2 protein was found to be 55% among HCV RNA-positive sera, and 53% among HCV RNA-negative sera. In conclusion, we have identified and characterized two major linear antigenic regions outside the two hypervariable regions of the e2 protein. Since these regions are accessible to the B cells of the infected host, these two regions are likely to be surface exposed either on the precursor polyprotein or the native e2 protein. Also, we could confirm that antibodies to the e2 protein co-exist with HCV viraemia.
Cross-regulatory role of interferon-gamma (IFN-γ), IL-4 and IL-10 in schistosome egg granuloma formation:in vivoregulation of Th activity and inflammation
Authors: CHENSUE S W , WARMINGTON K S , RUTH J , LINCOLN P M , KUNKEL S L 
Published: July 2010

SUMMARYThis study examined the relationship ofIL-4, IL-10 and IFN-γ with regard to the local granuloma (GR) and draining lymph node (LN) response to Schistosoma mansoni eggs. Synchronized GR were induced in naive and schistosome-infected mice at the vigorous (8 weeks) and late chronic (20 weeks) stages. In LN cultures, IL-10 and IFN production peaked on day 4 and was greatest for 8 week-infected mice. All GR cultures contained IFN, but compared with naive mice IL-10 production was accelerated at 8 weeks and abrogated at 20 weeks, consistent with expansion and abatement of Th2 activity, Cytokine neutralization was performed in egg-challenged, naive mice that were adoptively sensitized with lymphoid cells from 8 week-infected donors. GR size, GR macrophage tumour necrosis factor (TNF) production and egg antigen-elicited IL-2, IL-4, IL-5, IL-10 and IFN were examined on day 4 of GR formation, Anti-IFN augmented GR area by 40%, increased local IL-4 and IL-10, but decreased IFN and TNF production. In corresponding LN cultures, IFN decreased by about 50%, while IL-2, IL-4, IL-IO and lL-5 increased by nearly two-, four-, five- and six-fold, respectively, Anti-IL-10 did not affect GR size or GR cytokines, but increased IFN levels in LN cultures four-fold and decreased IL-2, IL-4, lL-5 and IL-10. Anti-IL-4 abrogated GR area by 40%, along with a reduction in local IL-4 and TNF production. In LN, IL-4 depletion reduced IL-4 and IL-5 by 60–70% and increased IFN levels. These results support the notion of a cross-regulatory network in which IFN inhibits Th2 and IL-10 inhibits ThI cells. IL-4 fosters Th2 cell differentiation in LN, but also performs a critical recruitment function in the eosinophil-rich schistosome egg-induced GR, whereas IFN contributes to enhanced GR macrophage function.
Evaluation of Onchocerca volvulus-specific IgG4 subclass serology as an index of onchocerciasis transmission potential of three Gabonese villages
Authors: EGWANG T G , DUONG T H , NGUIRI C , NGARI P , EVERAERE S , RICHARD-LENOBLE D , GBAKIMA A A , KOMBILA M 
Published: July 2010

SUMMARY
The major objective of this study was to evaluate the usefulness of IgG4 ELISA and Western blot analysis, using a crude extract of Onchocerca volvulus adult worms as antigens, for diagnosing onchocerciasis in a Gabonese paediatric population with mixed filarial infections. The subjects had loaisis, streptocercosis or mansonellosis in addition to onchocerciasis. Control sera from loaisis or mansonellosis subjects residing outside the endemic zone were used to provide the cut-off point for positive results. The IgG4 ELISA had a specificity of 96% but a lower sensitivity of 78·7%. It detected 25 onchocerciasis cases out of 65 individuals who were negative on parasitological examination. Furthermore, the ELISA provided a more accurate picture of onchocerciasis transmission in a village with very low skin microfilartal load. A 27·5-kD antigen was identified on Western blots as a marker of onchocerciasis. The paediatric population provided a reliable window for assessing the parasitologic and serologic parameters in the three villages with disparate levels of onchocerciasis transmission.
Suppression of experimental systemic lupus erythematosus (SLE) with specific anti-idiotypic antibody–saporin conjugate
Authors: BLANK M , MANOSROI J , TOMER Y , MANOSROI A , KOPOLOVIC J , CHARCON-POLAK S , SHOENFELD Y 
Published: July 2010

SUMMARYThe importance of the idiotypic network is represented in experimental SLE induced by active immunization of naive mice with an anti-DNA idiotype (Ab1) emulsified in adjuvant. The mice after 4 months of incubation generate Ab3 having anti-DNA activity. In addition, the mice develop other serological markers for SLE associated with clinical and histopathological manifestations characteristic of the disease. To confirm further the etiological role of the idiotype in this experimental model the mice were treated with specific anti-idiotypic antibodies (anti-id) which were also conjugated to a toxin-saporin (Immunotoxin (IT)). Pretreatment of hybridoma cell line producing the anti-anti-Id (anti-DNA = (Ab3)) for 48 h with the anti-Id MoAb (Ab2) reduced the production of anti-DNA by 58%, while pretreatment with the IT resulted in 86% decrease in anti-DNA secretion (saporin alone had only 12% effect). The anti-Id MoAb had no effect on the production of immunoglobulin by an unrelated cell line. In vivo treatment of mice with experimental SLE led to a significant decrease in titres of serum autoantibodies, with diminished clinical manifestations. The results were more remarkable when the IT was employed. These suppressive effects were specific, since an anti-Id treatment of experimental anti-phospholipid syndrome was of no avail. The anti-Id effect was mediated via a reduction in specific anti-DNA antibody-forming cells, and lasted only while anti-Id injections were given. Discontinuation of the anti-Id injection was followed by a rise in titres of anti-DNA antibodies. No immunological escape of new anti-DNA Ids was noted. Our results point to the importance of pathogenic idiotypes in SLE and to the specific potential of implementing anti-idiotypic therapy, enhanced by the conjugation of the anti-Id to an immunotoxin, in particular one with low spontaneous toxicity.
T cell reactivity to proteinase 3 and myeloperoxidase in patients with Wegener's granulomatosis (WG)
Authors: BROUWER E , STEGEMAN C A , HUITEMA M G , LIMBURG P C , KALLENBERG C G M 
Published: July 2010

SUMMARYT cell-mediated immunity is hypothesized to play an important role in the pathogenesis of granulomatous inflammation and vasculitis as found in patients with WG. The antigenic specificities of those T cells remain, however, unknown. Anti-neutrophil cytoplasmic antibodies (ANCA) present in patients with WG are directed to proteinase 3 (PR3) and myeloperoxidase (MPO). In the present study we investigated the proliferative capacity of peripheral Wood mononuclear cells (PBMC) from patients with WG and age-and sex-matched controls in response to the WG autoantigens PR3 and MPO. Possible mitogenic effects of active PR3 and toxic effects of active MPO were excluded by using heat-inactivated PR3 and MPO. Antigen-specific stimulation induced by these autoantigens was studied by using processed PR3 and MPO in the lymphocyte stimulation test (LST). Proliferation induced by processed antigen correlated with that by heat-inactivated free antigen. The general capacity to proliferate in response to mitogens and recall antigens did not differ between patients and controls. However, patients with WG who were or had been positive for PR3-ANCA (n = 17) responded more strongly to PR3 than to MPO and showed higher responses to PR3 compared with controls (n = 13). Within the PR3-ANCA group T cell proliferation did not correlate with ANCA titre. In a small group of patients with MPO-ANCA (n=5) no differences were observed compared with controls for MPO-specific proliferation. The data presented demonstrate that autoreactive PR3-specific T cells are present in patients with WG. Their fine specificity and possible role in the pathogenesis of WG have to be defined in further studies.
T cell receptor V-gene usage in oral lichen planus; increased frequency of T cell receptors expressing Vα2 and Vβ3
Authors: SIMARK-MATTSSON C , BERGENHOLTZ G , JONTELL M , TARKOWSKI A , DAHLGREN U I 
Published: July 2010

SUMMARY
In order to analyse the clonality of T cells in the inflammatory infiltrate of oral lichen planus (OLP), mucosal biopsies were obtained from seven patients with manifest disease. The biopsies were stained with MoAbs directed against 11 different T cell receptor (TCR) V-gene families, anti-CD4, anti-CD8 and lL-2 receptor (1L-2R). For comparison, the frequencies of the different TCR V-families were determined in biopsies from five patients with oral candidosis as well as in peripheral blood from three patients with OLP and from six healthy blood donors (HBD), The occurrence of the investigated TCR V-families varied between 0% and 7% in venous blood obtained from both HBD and OLP patients, T lymphocytes expressing the TCR Vβ3 and Vα2 in OLP biopsies were, however, detected in frequencies ranging between 18% and 40% of the total fraction of lymphocytes, a consistent finding for all the OLP infiltrates studied. The other nine TCR V-families examined appeared in low frequencies both in biopsies and in peripheral blood, Vα2+ and Vβ+β3+ cells were often localized adjacent to the basal membrane. In contrast, T cells in Candida-induced lesions did not express a biased TCR distribution, and most V-families studied appeared in frequencies of 0–6%. Thus, T lymphocytes in OLP lesions express a substantially higher frequency of TCR Vα2 and Vβ3 than expected from the distribution in blood. The clonal expansion of T cells observed in OLP suggests that a superantigen is involved in the pathogenesis of the disease. Whether this superantigen is of exogenous or endogenous origin needs to be investigated.
Immune complex-degradation ability of macrophages in MKL/Mp-lpr/lprlupus mice and its regulation by cytokines
Authors: KANNO H , TACHIWAKI O , NOSE M , KYOGOKU M 
Published: July 2010

SUMMARYImpaired clearance of circulating and/or deposited immune complexes (IC) by the mononuclear phagocylic system is one of the major factors in the pathogenesis of IC diseases. MRL/Mp-lpr/lpr (MRL/lpr) lupus mice spontaneously develop a lethal glomerulonephritis associated with IC deposition. The ability of macrophages to degrade phagocytozed IC and regulation of this degradation in MRL/lpr mice were examined. In 4-month-old MRL/lpr mice. Macrophages accumulated in the affected glomeruli and these macrophages contained many phagosomes containing electron-dense bodies. When culture supernatant of human T cell line HUT102 was administered intraperitoneally into disease-bearing MRL/lpr- mice, degradation of these electrondense bodies in the macrophages in glomeruli was noted. We developed a quantitative in vitro assay for IC degradation activity of MRL/lpr resident peritoneal macrophages (RPM) using peroxidase-labelled IC derived from MRL/lpr mouse sera. The ability of the RPM to degrade IC was remarkably enhanced by the pretreatment with HUT102 cell products and the related human recombinant cytokines lymphotoxin and IL-1α. Moreover, pretreatment of RPM from non-diseased MRL/Mp- +/+ mice with the culture supernatant of spleen cells from diseased MRL/lpr mice reduced their IC degradation activity. These results suggested that the ability of macrophages to degrade IC in MRL/Mp strains of mice is under the regulation of cytokines and the impaired ability in the disease-bearing mice may be the result of abnormalities in the cytokine system in these mice.
Regulation of human basophil activation; the role of Na+ and Ca2+in IL-3-induced potentiation of IgE-mediated histamine release from human basophils
Authors: BEAUVAIS F , ECHASSERIEAU K , BURTIN C , BENVENISTE J 
Published: July 2010

SUMMARYThe release of mediators from human basophils is strongly enhanced by lL-3. However, the signalling pathways of IL-3 arc poorly defined in these cells. Since external Ca2+ and Na+ play important regulating roles in histamine release, the possibility that these cations could be involved in the potentiation by rL-3 of the anti-IgE-induced histamine release from human basophils was considered, and it was observed that: (i) lL-3 dramatically decreased the external Ca2+ requirement for IgE-mediated histamine release. However, histamine release from IL-3-treated basophils became only partially independent of external Ca2+, since addition of EGTA in the external medium abolished the effect of IL-3; (ii) decreasing Na+ influx by lowering external Na+ concentration in isosmotic medium inhibited thepotenEiatiiigefTeLtoriL-3on IgE-mediated release; (iii) amiloride. An inhibitor of Na+/Ca2+ and Na+/H+ exchanges, and its derivative, benzamil, more specific for Na+/Ca2+ exchanges, inhibited the release potentiated by IL-3. In contrast, the amiloride derivative 5-(N, N-dimethy1)-amiloride more specific for Na+/H+ exchanges, slightly increased the IL-3-enhaneed release. Thus, the decreased requirement for external Ca2+ and the dependence on external Na + taken with the effect of the Na+/Ca2+ exchange inhibitors, suggest that Na+/Ca2+ exchanges are involved in the IL-3-indueed enhancement of IgE-mediated human basophil histamine release.
Dichotomy of the human T cell response toLeishmaniaantigens. I. Th1-like response toLeishmania majorpromastigote antigens in individuals recovered from cutaneous leishmaniasis
Authors: KEMP M , HEY A S , KURTZHALS J A L , RISTENSEN C B V C H , GAAFAR A , MUSTAFA M D , KORDOFANI A A Y , ISMAIL A , KHARAZMI A , THEANDER T G 
Published: July 2010

SUMMARYThe T cell response to antigens from Leishmania major promastigotes was investigated in peripheral blood mononuclear cells from Sudanese individuals with a history of cutaneous leishmaniasis (CL), Sudanese individuals with positive DTH reaction in the leishmanin skin test but with no history of skin lesions, and in Danes without known exposure to Leishmania parasites. Proliferation and production of interferon-gamma (IFN-γ) and IL-4 in antigen-stimulated cultures was measured. Lymphocytes from individuals with a history of CL proliferated vigorously and produced IFN-γ after stimulation with either a crude preparation of L. major antigens or the major surface protease gp63. These cultures produced no or only little IL-4. Also cells from leishmanin skin test-positive donors with no history of CL produced IFN-γ and no IL-4 in response to major antigens. Cells from the unexposed Danes were not activated by gp63. The cells from Danish donors produced either IFN-γ or IL-4, but not both cytokines after incubation with the crude preparation of L. major antigens. The data show that the T cell response to Leishmania antigens in humans who have had uncomplicated CL or subclinical L. major infection is an IFN-γ-producing Th1-like response.
Augmentation of antigen-specific lymphoproliferative responsesin vitroby biological response modifiers
Authors: GRUIJL T D D E , MOORE J J , DE VRIES E , VON BLOMBERG-VAN DER FLIER B M E , FONK J C M , SCHEPER R J 
Published: July 2010

SUMMARYThe detection of antigen-specific T cell responsiveness, particularly of resting memory lymphocytes, in cultures of peripheral blood mononuclear cells (PBMC) may be hampered by a less than optimal antigen presentation in vitro. Augmented sensitivity of the test system may be achieved by the addition of reagents with a beneficial effect on lymphocyte and antigen-presenting cell (APC) functions. In this study the effect of several biological response modifiers on antigen-specific T cell proliferation was determined, using nickel sulphate and tetanus toxoid as lest antigens. IL-lα (100 U/ml). interferon-gamma (IFN-γ) (10 U/ml), and indomethacin (2 μM) were found to significantly enhance nickel-induced proliferation in PBMC cultures from nickel-hypersensitive donors (n = 6). Tetanus-induced proliferation (n = 5) was similarly enhanced, both by the above supplements and by the addition of polyethylene glycol (PEG) or a neuraminidase treatment of the PBMC before culture. The addition to PBMC cultures of a combination of IL-lα (30 U/ml), IFN-γ (10 U/ml), and indomethacin (2 μM) is recommended to specifically enhance antigen-induced lymphoproliferative signals.
Pathogenic natural anti-cardiolipin antibodies: the experience from monoclonal gammopathy
Authors: COHEN J , BAKIMER R , BLANK M , VALESINI G , SHOENFELD Y 
Published: July 2010

SUMMARY
Anti-cardiolipin antibodies (ACA) were detected in 19% of sera from patients with monoclonal gammopathies (MG). ACA were purified from the sera of patients with MG. One of the IgG-ACA was found to be monospecific with high affinity for cardiolipin, and to carry a pathogenic ACA Id (1.10), Active immunization of naive BALB/c mice with the puri6ed IgG-ACA was followed by production in the mice of sustained high titres of ACA, associated with prolonged activated partial thromboplastin time (APTT) (61 ± 14s versus 31 ± 2 s in control mice; P &lt; 0.001) and thrombocytopenia (468 000 ± 224 000/mm3 versus 994 000 ± 92 000/mm3 in controls; P &lt; 0001). The titres of other autoantibodies (e.g. anti-DNA, anti-histones), although being high after immunization, decreased rapidly and were undetected after 1 month following the boost injection. The mice immunized with the IgG-ACA exhibited low fecundity (36% of mice became pregnant versus 62% observed in the group immunized with control IgG). The pregnant mice had increased resorption rate (the equivalent of fetal loss in the human) of 52 ± 8% (versus 5 ± 4% in the control group). The mean (±s.d.) embryo and placental weights in mice with anti-phospholipid syndrome (APLS) were significantly lower compared with the mice injected with control IgG (682 ± 304 mg and 102±12mg versus 1303 ± 105 mg and 145±8mg, respectively; P&lt;0.001). Serum monoclonal immunoglobulins having autoantibody activity may be regarded as an expansion of clones producing natural autoantibodies. Our results confirm the pathogenic role of natural ACA in the pathogenesis of the anti-phospholipid syndrome.
Persistence of a rheumatoid factor (RF)-producing B cell clone with a somatically mutated Igκ chain in a patient with rheumatoid arthritis
Authors: SCHRAUDER A , GAUSE A , JUNG W , MIERAU R , PFREUNDSCHUH M 
Published: July 2010

SUMMARYThe VκIV gene encoding the light chain of an IgA RF has been shown to have undergone 31 somatic mutations compared with the single existing VκIV germ-line gene. We now show the persistence of the rearranged and mutated DNA coding for this RF over a period of 5 years in the peripheral blood lymphocytes (PBL) of the patient with rheumatoid arthritis (RA). The sequence of the RF has been conserved to identity over this period. These results raise the possibility that the particular antigenic stimulus leading to RF production in this RA patient is active over a long period of time.
Enhanced generation of reactive oxygen species in monocytes from patients with common variable immunodeficiency
Authors: AUKKUST P , MÜLLER F , FRØLAND S S 
Published: July 2010

SUMMARYMonocyte and macrophage dysfunction may be important for both immunopathogenesis and clinical manifestations in subgroups of patients with primary hypogammaglobulinaemia. In the present study we examined the ability to generate reactive oxygen species (ROS) in isolated monocytes from these patients by two different methods: superoxide dismutase (SOD) inhibitable cytochrome c reduction by O2− and nitroblue tetrazolium (NBT) reduction. Monocytes from patients with common variable immunodeficiency (CVI) demonstrated significantly enhanced ROS generation both unstimulated and stimulated (unopsonized zymosan and phorbol myristate acetate (PMA)). The enhanced oxidative burst response in CVI patients was found both with and without scrum containing medium. Furthermore, serum from CVI patients did significantly enhance the oxidative burst response in monocytes from healthy blood donors compared with the effect of control serum. The enhanced ROS generation in CVI patients was significantly correlated with elevated serum levels of neopterin, reduced numbers of CD4+ lymphocytes in peripheral blood and occurrence of splenomegaly. In contrast to the CVI group, monocytes from patients with X-linked agammaglobulinaemia (XLA) did not show enhanced ROS generation. The increased oxidative burst response in monocytes from CVI patients most probably reflects in vivo activation of these cells. Our observations indicate the presence of a subgroup of CVI patients characterized by chronic immune activation particularly of monocytes. The enhanced ROS generation might be involved in immunopathogenesis (e.g. T cell dysfunction) and in the pathogenesis of clinical manifestations (e.g. malignancies and autoimmune disorders) in these patients.
Serum soluble CD23 in patients with hypogammaglobulinaemia
Authors: BANSAL A S , HAENEY M R , COCHRANE S , PUMPHREY R S H , GREEN L M , BHAVNANI M , WILSON P B 
Published: July 2010

SUMMARY
Serum levels of the soluble form of the low-affinity receptor for IgE (FcERII, CD23) (sCD23) are elevated in autoimmune conditions associated with hypergammaglobulinaemia and B cell hyperactivity. Very high levels of sCD23 are found in patients with B-chronic lymphatic leukaemia (B-CLL) who are, however, frequently hypogammaglobulinaemic. We therefore compared the serum levels of sCD23 in healthy controls (n= 33) with three conditions associated with hypogammaglobulinaemia (HGG) and varying B cell numbers: X-linked agammaglobulinaemia (XLA, n= 12), common variable immunodeficiency (CVI, n= 20) and B-chronic lymphatic leukaemia (n= 33). Serum levels of sCD23 showed a significant correlation with the CD19+ B cell count in both normals and patients with CVI (r= 0 65, P &lt; 0·0001). Amongst the different clinical groups, serum levels of sCD23 were increased in the order XLA &lt; CVI &lt; normals &lt; CLL (medians 2·5, 7·7, 11·1 and 540, respectively; P &lt; 0·001 for all comparisons except CVI versus normals P &lt; 0·03 in a one-tailed test). In the CVI group, serum sCD23 was lowest amongst four patients with low B cell numbers. There was no overlap in sCD23 between patients with XLA and this subgroup of CVI patients. Serum sCD23 is, therefore, derived predominantly from B cells, and is significantly related to the peripheral blood B cell count.