bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human anti-mouse antibody response to the injection of murine monoclonal antibodies against IL-6
Authors: LEGOUFFE E , LIAUTARD J , GAILLARD J P , ROSSI J-F , WIJDENES J , BATAILLE R , KLEIN B , BROCHIER J 
Published: July 2010

SUMMARYWe analysed human anti-mouse antibodies (HAMA) in 12 patients (six with multiple myeloma (MM) and six with metastatic renal cell carcinoma (MRCC)) who were treated with B-E8, an IgG1 MoAb against IL-6. Efficiency of the treatment was evidenced by the drop in the serum levels of C-reactive protein (CRP), the in vivo production of which is under the control of IL-6. Three patients with MM and the six patients with MRCC became immunized m the injected MoAb. HAMA appeared between days 7 and 15 after the beginning of the treatment. The nine patients made IgG antibodies: four also made IgM. All immunized patients made anti-biotype antibodies specific to B-E8. Two of them also developed HAMA directed to murine IgG1 isotype: in these two patients B-E8 MoAb cleared rapidly from the circulation with loss of treatment efficiency. In the patients who developed only anti-biotype antibodies, serum levels of B-E8 remained unchanged and CRP production remained inhibited, indicating that treatment remained efficient in the presence of HAMA, Circulating B-E8 MoAbs were still able to bind to iL-6 and to inhibit IL-6-dependent proliferation despite the presence of anti-idiotypic HAMA, Therefore, in contrast to HAMA produced against MoAb directed against cellular targets, HAMA against anti-IL-6 MoAb idiotopes led neither to clearance nor to functional inactivation of the injected MoAb. This was further shown by resuming the B-E8 treatment with success in a patient who still had anti-idiotypic HAMA.
The significance of the pre-challenge immune status of mice for development of retrovirus-induced immunodeficiency syndrome (MAIDS)
Authors: PAVLOVITCH J H , RIZK-RABIN M , PICARD F , MARUSSIG M , HALBREICH A 
Published: July 2010

SUMMARYThe effects of vaccination with RNA-free viral pseudoparticles, preinfection with non-pathogenic ecotropic virus, and induction of tolerance to viral proteins in newborns on the outcome of murine immunodeficiency syndrome (MAIDS) were studied. The parameters used to follow disease progression were: lymphopenia, circulating B and T8 cells, serum IgG and IgM levels, lymphoproliferation and skin graft rejection, [minimization with RNA-free viral pseudoparticles had no effect on any of these parameters. Preinfection of adults with ecotropic virus and the induction of tolerance in newborns to virus antigens both attenuated the early symptoms of viral infection and delayed the onset of immunodeficiency and lympho-proliferation in some mice, but did not significantly alter the number of deaths due to MAIDS. Failure of immune-based therapy to produce successful protection against MAIDS suggests that immune destruction caused by the persistent virus rather than hyper immune activity is the main pathogenic factor in this disease.
Comparison of the immune response against Mycobacterium tuberculosis antigens between a group of patients with active pulmonary tuberculosis and healthy household contacts
Authors: TORRES M , MENDEZ-SAMPEIRO P , JIMENEZ-ZAMUDIO L , TERAN L , CAMARENA A , QUEZADA R , RAMOS E , SADA E 
Published: July 2010

SUMMARYThe mycobacterial antigens and the factors related to protection for the development of active tuberculosis are not known. In a natural model of tuberculosis, we studied 10 patients with active pulmonary tuberculosis (non-protective immune response) and 38 healthy household contacts (protective immune response). We tested the lymphocyte proliferative response by T cell Western blotting to eight different antigen fractions and lo two purified mycobacterial antigens of 30 and 64 kD. Patients with active tuberculosis recognized fractions with molecular weights of 80–114, 60–80, 28–41 and 14–19kD. Household contacts recognized the same fractions except the 14–19 kD. The response lo the 64-kD antigen was not significantly different between groups. In contrast, 10% of the patients with active tuberculosis and 73% of the household contacts responded to the 30-kD antigen. The humoral response against the 30-kD antigen by ELISA showed a significantly higher production of antibodies in tuberculosis patients compared with household contacts. We conclude that patients with active pulmonary tuberculosis develop an immune response characterized by poor proliferative response to the 30-kD antigen with a strong humoral response, whereas the opposite occurs in healthy subjects infected by Mycobacterium tuberculoses.
Surface molecules involved in the adherence of recombinant interferon-gamma (rIFN-γ)-stimulated human monocytes to vascular endothelial cells
Authors: WANG J , BEEKHUIZEN H , VAN FURTH R 
Published: July 2010

SUMMARYDuring an inflammatory reaction, an increased number of circulating monocytes adhere to the endothelial cells (EC) of the vessel wall. This process is mediated by molecules located on the surface of monocytes and EC. Locally released Inflammatory mediators can modulate monocyte EC interaction. In an earlier study we reported that stimulation of monolayers of cultured venous EC with rIFN-γ enhanced their adhesiveness for monocytes. The aim of the present study was to investigate the effect of rIFN-γ on peripheral blood monocytes with regard to the expression of surface molecules and the binding to non-stimulated or cytokine-stimulated EC. Flow cytometric analysis demonstrated that monocytes stimulated with 500 U/ml rIFN-γ for 24 h showed increased expression of CR3 (CDIIb;CD18), p150,95 (CD11c/CD18) and Fc-γ (CD64); the expression of LFA-1 (CD11 la/CD18). L-selectin, CD14 and VLA-4 (CD49d/CD29) did not change or was slightly reduced. Upon stimulation with rIFN-γ monocytes showed an enhanced binding to both nonstimulated or rIFN-γ-stimulated EC. This was even more pronounced when EC had been stimulated with rIL-lα for 24 h. The increased binding of rIFN-γstimulated monocytes to rIL-lα-stimulated EC was further analysed. Studies with MoAbs against adhesion molecules on monocytes revealed that the binding of rIFN-γ-stimulated monocytes, hut not that of non-stimulated monocytes, to rIL-lα stimulated EC was inhibited by about 30–60% with MoAbs against CD11a. CDllb, CD18, L-selectin or CD14. MoAbs againsi CD11c or CD49d had little or no effect. From these results, we conclude that exposure of monocytes to rIFN-γ enhances their adhesiveness to cytokine-stimulated EC by a mechanism which involves CD11a/CD18, CD11b/CD18, CD14 and L-selectin on monocytes.
Antibody reactivity to an Epstein–Barr virus BERF4-encoded epitope occurring also in Asp-57 region of HLA-DQ8 β chain
Authors:   THE CHILDHOOD DIABETES IN FINLAND STUDY GROUP, PARKKONEN P , HYÖTY H , ILONEN J , REIJONEN H , YLÄ-HERTTUALA S , LEINIKKI P 
Published: July 2010

SUMMARYA five amino acids-long sequence (GPPAA) in the region of the 57th amino acid of HIA-DQ8 β chain, with seems to be important in defining the risk for type I diabetes, occurs also in the BERF4-encoded EBNA 3C protein of Epstein-Barr virus (EBV) in six successive repeats. The antigenicity of this region was analysed using synthetic peptides containing different modifications of the GPPAA sequence. Two of the seven individuals who had acute EBV infection produced antibodies against an EBV-derived peptide (GPPAAGPPAAGPPAA) paralleling the EBNA2 antibodies. These two cases also contracted type I diabetes immediately after the infection. High antibody levels against this peptide were found in a total of 12%, of EBV+ individuals, and in most cases antibodies remained at high levels for several years. Human sera as well as affinity-purified antibodies specific for the GPPAAGPPAAGPPAA peptide reacted also with shorter peptide analogues (GPPAAGPPAA and GPPAA), as well as with peptides containing the surrounding motifs from DQ8 β chains. However, none of these antibodies bound to denatured DQ8 β chains in immunoblotting. The charge of the 57th amino acid modulated the antigenicity of this epitope, as peptides from Asp-57-negative DQ molecules were reactive, while peptides from Asp-57-positive DQ molecules were not. The responsiveness was seen in both HLA-DQ8-positive and -negative subjects as well as in type I diabetic individuals. The results suggest that some individuals who carry the GPPAA sequence in their HLA-DQ molecule recognize this epitope in EBV. This phenomenon may have potential importance in EBV-induced immune abnormalities, although cross-reactivity against DQ molecules could not be demonstrated in the present study.
IgG2 subclass restriction of anti-β2 glycoprotein 1 antibodies in autoimmune patients
Authors: ARVIEUX J , ROUSSEL B , PONARD D , COLOMB M G 
Published: July 2010

SUMMARY
The IgG subclass and light chain distribution of antiphospholipid antibodies (aPL) occurring in autoimmune patients were determined by means of two radioimmunoassays using either cardiolipinor β2 glycoprotein 1 (β2GP1)-coated microtitre plates and mouse MoAbs. Of 50 sera selected for positivity of anticardiolipin antibodies (ACA) of the IgG isotype, 32 (64%) possessed anti-β2GPl antibodies and their presence was closely associated with clinical features of the antiphospholipid syndrome. Good correlations were found between ACA and anti-β2GP1 antibodies when considering antibody level and patterns of light chain and IgG subclass, suggesting that, overall, the same antibodies were being measured. Light chain analysis showed the polyclonal origin of these antibodies and, in most sera, a trend towards use of λ chain. Among sera positive for anti-β2GP1 antibodies, IgG2 was the major subclass reactive with β2GP1 and cardiolipin (87% and 74β2 of the IgG antibody activity, respectively). In contrast, in the group of 18 sera lacking anti-β2GP1 antibodies, ACA were largely restricted to lgG3, with a lesser contribution by IgGl. A few selected sera from the anti-β2GP1-positive group were shown to contain mixtures of antibodies that required β2GP1 (restricted to IgG2 present in large amounts) and did not require this cofactor (restricted to IgG3 and/or IgG1 present in low amounts) for their reactivity with cardiolipin. There was no contribution of glycosylation to the epitopes recognized by anti-β2GP1 antibodies, even though human anti-carbohydrate antibodies are restricted to the IgG2 subclass. These findings further emphasize the intra- and interindividual heterogeneity of aPL, and should help to discriminate clinically relevant specificies.
Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinicalOnchocerca volvulusinfection
Authors: SOBOSLAY P T , LÜDER C G K , HOFFMANN W H , MICHAELIS I , HELLING G , HEUSCHKEL C , DREWECK C M , BLANKE C H , PRITZE S , BANLA M , SCHULZ-KEY H 
Published: July 2010

SUMMARYThe present study examined the quantitative and qualitative changes registered in the parasite-specific antibody response, cellular reactivity and cytokine production profile in onchocerciasis patients repeatedly treated with ivermectin over a period of 8 years. The densities of Onchocerca volvulus microfilariae (mf) in treated patients remained significantly reduced, whereas the number of permanently amicrofilaridermic patients (subclinical infection) increased with repeated treatments. In vitro cellular responses to O. volvulus antigen (OvAg) were highest (P&lt;0.001) in untreated control individuals exposed to infection, but negative for mf of O. volvulus (endemic normals). Cellular reactivity in repeatedly treated patients was higher at 84 than at 36 months post initial treatment (p.i.t.); furthermore, the proliferative responses to OvAg, mycobacterial purified protein derivative (PPD) and streptococcal SL-O were greater (P&lt;0·05) at 84 months p.i.t. in amicrofilaridermic than in microfilaria-positive onchocerciasis patients. In amicrofilaridermic patients such reactivity approached the magnitude observed in endemic normals. Peripheral blood mononuclear cells (PBMC) from patients and endemic normals produced equivalent amounts of IL-2. IL-4 and interferon-gamma (IFN-γ) in response to mitogenic stimulation with phytohaemagglutinin (PHA); in response to OvAg, however, significantly more IL-2 and IFN-γ were produced by PBMC from subclinical amicrofilaridermic patients or endemic normals than by mf-positive patients OvAg-specific production or IL-4 by PBMC from treated patients was lower at 84 than at 36 months p.i.t. At three months p.i.t. the titres of circulating OvAg-specific IgG1-3 had increased (P&lt;0·05), but they then continuously declined with repeated treatments. Only IgG1 and IgG4 bound to OvAg of mol. wt 2-l2 kD at 1 month p.i.t., while recognition of OvAg of mol. wt 10–200 kD by IgG1, IgG2 and IgG4 reached a maximum intensity at 3–6 months p.i.t., with the overall intensity of binding to OvAg gradually weakening thereafter. These results suggest that onchocerciasis-associated immuno-suppression is reversible following ivermectin-induced permanent clearance of microfilariae from the skin; and that a vigorous parasite-specific cellular reactivity and a sustained production of IL-2 and IFN-γ in amicrofilaridermic individuals may contribute to controlling O. volvulus infection.
Selective induction of anti-fibrillarin autoantibodies by silver nitrate in mice
Authors: HULTMAN P , ENESTRÖM S , TURLEY S J , POLLARD K M 
Published: July 2010

SUMMARYFemale SJL (H-2s) mice developed serum IgG anti-nucleolar antibodies (ANoA) after 5 weeks treatment with 0·05% or 0·01% silver nitrate (AgNO3) in drinking water. Five more weeks of treatment increased the ANoA titre to 3410 ± 853 and 640±175 (reciprocal mean ± s.e.m.), respectively. Controls receiving ordinary tap water and mice given 0·002% AgNO3, showed no antinucleolar antibodies. The high-titre ANoA targeted a 34-kD nucleolar protein identified as fibrillarin, the major autoantigen in murine mercury-induced autoimmunity and in a fraction of patients with systemic scleroderma. Serum autoantibodies to chromatin or histones, kidney, spleen, stomach, thyroid, or skin antigens (except the nucleolus) were not found in any of the mice. There was no consistent significant increase of serum IgG1 igG2a, IgG2b, or IgG3 concentrations after AgNO3 treatment compared with controls. Mice treated with 0·05% AgNO3 for 10 weeks showed a slight decrease in serum IgG1, IgG2b and lgG3 concentrations. These mice also showed a small but statistically significant increase in renal, mesangial IgM deposits, which was not accompanied by any increase in C3c deposits, whereas mice given lower doses of silver nitrate showed no significant increase in mesangial immunoglobulin immune deposits. Systemic vessel wall immune deposits were not found in any of the mice. In mice given 0·05% silver nitrate, the kidney showed the highest concentration of silver (12·2±0·09 μg Ag/g wet weight; mean ± s.e.m.). followed by the spleen (8·7±1·3), and the liver (3·9±0·4). Treatment with 0·01% silver nitrate caused a different distribution of silver, with the highest concentration in the spleen (2·1±0·16 μg Ag/g), followed by the kidney (0·63±0·037), and the liver (&lt; 0·29 μg Ag/g; mean). Silver seems to be a more specific inducer of antinucleolar/anti-fibrillarin autoantibodies than mercury and gold, lacks the general immune stimulating potential of mercury, and has only a weak tendency to induce renal immune deposits. These observations suggest that the autoimmune sequelae induced in mice by metals is dependent, not only upon the genetic haplotype of the murine strain, but also on the metal under investigation.
Modulation of the IL-2 production defectin vitroin Graves'disease
Authors: EISENSTEIN Z , ENGELSMAN E , WEISS M , KALECHMAN Y , SREDNI B 
Published: July 2010

SUMMARYIL-2 production by mitogen-induced peripheral blood mononuclear cells was reported to be reduced in several autoimmune diseases, including Graves'disease (GD). This production defect in hyperthyroid GD was restored to normal by antithyroid drug therapy or during remission. However, its underlying mechanism and role in the autoimmune process are still uncertain. The present study was undertaken in order to screen the in vitro IL-2 generating system for putative factors responsible for its failure, and to see to what extent this was reversible. Thyroid hormone or antithyroid drugs had no effect on IL-2 production in vitro. Cultures were found lo be free of soluble inhibitors of IL-2 production or action. IL-1 deficiency as a cause of the IL-2 defect was ruled out; rather, Graves'adherent cells were found to be activated in being capable of secreting large amounts of IL-1 and prostaglandin E2: (PGE2). The latter was not found to be responsible for the decreased IL-2 production, IL-2 production by Graves'mononuclears was completely restored to normal by: (i) adherent cell depletion, irradiation or substitution with normal adherent cells; (ii) preincubation of mononuclears for 24–72 h before mitogen stimulation; (iii) the synergistic action of a phorbol ester and a calcium ionophore. These data indicate that inhibition by activated adherent ceils accounts for the in vitro IL-2 production defect in GD. This inhibition is not mediated by soluble factors, but probably through direct interaction with the producing cells, and is reversible in rested cultures or through a bypassed signal transduction.
Invasive amoebiasis is associated with the development of anti-neutrophil cytoplasmic antibody
Authors: PUDIFIN D J , DUURSMA J , GATHIRAM V , JACKSON T F H G 
Published: July 2010

SUMMARY
Features of tissue damage in invasive amoebiasis, in particular polymorphonuclear neutrophil (PMN) degranulation and vasculitis, bear resemblance to that seen in Wegener's granulomatosis, the latter being associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). We therefore tested sera from patients with confirmed amoebic liver abscess (ALA) for the presence of ANCA by means of an indirect fluorescent antibody test using pure neutrophils as substrate. ANCA was detected in 97·4% of amoebic sera: the pattern of staining was cytoplasmic, homogeneous, without central accentuation (C-ANCA). A proteinase 3 (PR3) ELISA demonstrated PR3 specificity in 75% of C-ANCA-positive ALA sera. Possible explanations are (i) a cross-reacting antibody to a component of Entamoeba histolytica, or (ii) an antibody to PMN components released, and possibly modified, by the action of E. histolytica on PMN. It is possible that this antibody contributes to the pathogenesis of invasive amoebiasis.
Inhibition of HIV replication by CD8+ T cells correlates with CD4 counts and clinical stage of disease
Authors: GÓMEZ A M , SMAILL F M , ROSENTHAL K L 
Published: July 2010

SUMMARYWe sought to evaluate the relationship of CD8+ T cell-mediated inhibition of autologous HIV replication in vitro to disease stage in HIV+ individuals. Depletion of CD8+ T cells from peripheral blood lymphocytes of 16 HIV+ subjects increased the percentage of virus-producing cultures from 56% to 81%. CD4+ T cells were purified from 52 HIV+ individuals and cultured alone or in the presence of autologous CD8+ T cells. In 13 (25%) subjects HIV replication was only detected in the absence of CD8+ T cells (inhibition positive); in 26 (50%) viral replication occurred both in the absence and presence of CD8+ cells (inhibition negative). In the remaining 13 (25%) subjects, CD8+ T cell-mediated inhibitory activity could not be evaluated because stimulation of their purified CD4+ T cells did not result in p24 production. In some virus culture-negative individuals, the inability to demonstrate HIV replication was due to the presence of low numbers of CD8+ T cells that co-purified with CD4+ T cells. Detection of inhibitory CD8+ T cells was associated with significantly higher CD4 counts and better clinical status compared with inhibition-negative subjects. These results demonstrate that CD8+ T cell-mediated inhibition of HIV replication correlates with disease stage, and thus may play a role in preventing disease progression. CD8+ T cells did not inhibit autologous HIV replication across a semipermeable membrane. Further, the ability of CD8+ T cells to prevent HIV replication did not correlate with lysis of autologous CD4+ T cells. Thus, CD8+ T cells inhibited autologous HIV replication in vitro through a contact mediated non-lytic mechanism.
Pathogenicity and immunogenicity ofParacoccidioides brasiliensisisolates in the human disease and in an experimental murine model
Authors: SINGER-VERMES L M , BURGER E , CALICH V L G , MODESTO-XAVIER L H , SAKAMOTO T N , SUGIZAKl M F , MEIRA D A , MENDES R P 
Published: July 2010

SUMMARYThe pathogenicity and immunogenicity of six recently isolated Paracoccidioides brasiliensis samples derived from patients presenting distinct and well defined clinical forms of paracoccidioidomycosis (PCM) were compared as to their virulence, tropism to different organs and ability to induce specific cellular and humoral immune response in susceptible (B10.A) inbred mice. Isolates Pb44 and Pb47 were obtained from acute cases, Pb50 from a chronic severe form, Pb45 from a chronic moderate ease and both Pb56 and Pb57 from chronic mild forms of PCM. Pathogenicity and tropism of each fungal sample were evaluated by LD50% estimation, examination of gross lesions on various organs at 2, 4, 12 and 16 weeks post-in feet ion, and by colony-forming unit (CFU) counts in the lungs at week 16 post-infection of mice. Fungal tropism in human PCM and in B10. A mice was always dissociated. A well defined relationship between virulence of the fungal sample and the clinical findings of the correspondent patient was not evident, although a tendency to higher LD50% and less intense paracoccidioidic lesions was observed in mice infected with Pb56 and Pb57. The specific DTH response patterns varied according to the infectant sample, but positive DTH reactions at the beginning of the infection and a tendency to anergy or low DTH responses at week 12 and/or week 16 post-infection were always observed. A correspondence between the DTH response in humans and in mice was noticeable only when the isolates from the most benign cases (Pb56 and Pb57) were considered. The specific antibody patterns in mice and in the correspondent patients were also not analogous. Collectively, these results indicate that an association between the fungal pathogenicity and immunogenicity in the human disease and in susceptible mice was discernible only when isolates obtained from very mild eases (Pb56 and Pb57) were considered.
Eicosapentaenoic acid modulates neutrophil leukotriene B4 receptor expression in cystic fibrosis
Authors: LAWRENCE R H , SORRELL T C 
Published: July 2010

SUMMARYIn patients with cystic fibrosis (CF), high intrapulmonary concentrations of the neutrophil chemotaxin leukotriene B4(LTB4) are associated with specific reduction of LTB4-induced chemotaxis of circulating neutrophils. The chemotactic abnormality is partially corrected by dietary supplementation with eicosapentaenoic acid (EPA). LTB4-induced neutrophil chemotaxis is mediated by specific, high-affinity, cell surface LTB4 receptors. The hypotheses that neutrophil LTB4 receptors are down-regulated in CF, and that EPA normalizes receptor expression, were tested by measuring the number (Rmax) and affinity (Kd) of LTB4 receptors on neutrophils from eight CF patients before and after EPA (6 weeks of 2–7g/day), and from nine normal individuals. High-affinity receptor Rmax was depressed in CF patients (0·6 ± 0·2 × 104/cell (mean ± s.d.) versus 1·8 ± 0·7 × 104/cell in normals), but corrected to normal (2·0 ± 1·9 × 104/cell) after EPA. High-affinity receptor Kd was depressed in CF patients (0·4 ± 0·3 nM versus 1·4 ± 0·5 nM in normals), and also corrected to normal with EPA (1·4 ± 1·2 nM). Low-affinity receptors were depressed, but did not change significantly with EPA. These results indicate that neutrophil responses in chronic inflammatory lung disease can be influenced directly by LTB4 receptor modulation, and that this effect of EPA predominates over alterations in neutrophil signal transduction in situations of chronic exposure to LTB4.