bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of cross-reactive idiotype-positive rheumatoid factor produced in autoimmune rheumatic diseases. An indicator of clonality and B cell proliferative mechanisms
Authors: SHOKRI F , MAGEED R A K , KITAS G D , KATSIKIS P , MOUTSOPOULOS H M , JEFFERIS R 
Published: July 2010

SUMMARYThe aetiology of sustained autoantibody production in human autoimmune diseases is unknown. Evidence for structural similarities and common clonal origin among autoantibodies have been demonstrated through the expression or cross-reactive idioiype (CRI). In the present study we use four monoclonal antibodies (MoAbs) with specificity for non-overlapping CRI on human rheumatoid factor (RF) autoantibodies to define the structural features of polyclonal RF characteristic of patients with autoimmune rheumatic diseases. The pattern of CRI expression in the scrum of 12 patients with rheumatoid arthritis (RA), eight with systemic lupus crythcmalosus(SLE) and 20 with primary Sjögren’s syndrome and 34 normal individuals were determined in parallel with the level of igM RF. IgA RF and autoantibodies to the cellular antigens SS-A. SS-B. Sm. nRNP and dsDN A and cryoglobulins. The results demonstrate significant elevation in the level of IgM and IgA expressing VHI (G6 and G8) and YHl 11 (B6 and Dl2) associated CRI in the scrum of patients with autoimmune rheumatic diseases compared with normal individuals. These increases paralleled, but did not equal the increase in the level of immunoglobulins and RF. However, when expressed as proportion of immunoglobulin. only the VHI-associated CRI were significantly elevated in patients compared with normal individuals. The proportion of IgM RF expressing the VMI -associated CRI was higher in patients with Sjdgrcn’s syndrome compared with SLE and RA. Furthermore, the proportion of IgA RF expressing the G6 CRI was higher than G66 IgM RF. These findings imply that different mechanisms contribute to RF production in autoimmune diseases. It is suggested thai polyconal B cell activation is likely to be a contributing mechanism. However, such polyclonal activation is unlikely to be random since a selective elevation in the level of specific autoantibodies and VMI -associated CRI is observed. Furthermore, the data demonstrate that a proportion of autoanlibodies in autoimmune diseases arc immunoglobulin gcrmline gene encoded. This is more evident in some patients with primary Sjogrcn’s syndrome, where RF is likely to be oligoclonal or monoclonal in individuals with lymphoprolifcration.
Contribution of the spleen, lymph nodes and bone marrow to the antibody response in collagen-induced arthritis in the rat
Authors: RAHMAN J , STAINES N A 
Published: July 2010

SUMMARYThe relative contribution of different lymphoid tissues to the anti-CII antibody response was studied in rats with arthritis produced as a result of immunizing them with collagen type II (CII). Antibody production was measured by maintaining lymphoid cells in short-term culture in collagen-coated microculture wells: the antibody they secreted was determined directly by a modified ELISA. Systemic sensitization to CII was established within a week of immunization, and a stronger response in the local draining lymph nodes relative to the spleen was associated with the development of clinical disease. From experiments involving splenectomy and adoptive cell transfer, the spleen was ascribed a suppressive role in controlling both arthritis and total antibody production. The bone marrow was found to be an important site of antibody production and the greater production of antibody by cells from tibial marrow in limbs with arthritis, compared with healthy limbs, argues for a local immune response to degrading joint antigens that may have systemic suppressive or protective properties. It is concluded that local immunity reflects the state of disease and that the antibodies produced by different lymphoid tissues may be made in response to different stimuli, and that the antibodies in turn may have different pathological effects.
T cell interactions in active rheumatoid arthritis: insights from the human autologous mixed lymphocyte reaction as a model of T cell activation cascade
Authors: SAKANE T , MURAKAWA Y , TAKENO M , SHIGEKI T , NAGAFUCHI H , MIKI T 
Published: July 2010

SUMMARYThe autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Using monoclonal anti-Leu8 antibody to isolate subpopulations of human CD4+ and CD8+ T cells, we have investigated the role of these subpopulations in the T cell activation cascade during the course of AMLR. In normal subjects, CD4+ Leu8+ cells are necessary for the initiation of the AMLR response, and sequentially lead to activation and proliferation of both CD4+ Leu8- cells and CD8+ Lcu8+ cells. The activated CD8+Lcu8+ cells, in turn, induce CD8+ Leu8- cells to generate proliferation of the latter cells. Soluble mediators could be involved in the T cell activation cascade induced by the AMLR. Patients with active rheumatoid arthritis have a profound defect in the AMLR. Further analysis indicates that rheumatoid arthritis CD8+ T cells are markedly defective as responding cells in the AMLR. The impaired AMLR response by CD8+ cells cannot be reconstituted with AMLR-derived supernatants from normal T cells. The data suggest that the defective CD8+ T cell function may contribute to the pathogenesis of the disease.
Detection of circulating FcɛR2/CD23+ monocytes in patients with rheumatic diseases
Authors: BECKER H , POTYKA P , WEBER C , FEDERLIN K 
Published: July 2010

SUMMARYRecently, in vitro studies have demonstrated that expression of FcɛR2/CD23 on normal monocytes can be specifically induced by IL-4. In order to investigate the interaction of IL-4 and monocytes in rheumatic diseases, flow cytometry studies were performed. Elevated numbers of circulating FcɛR2/ CD23+ monocytes were detected in patients with progressive systemic sclerosis (PSS) as compared with controls, in addition, supernatants derived from phytohaemagglutinin-stimulated peripheral blood mononuclear cells of PSS patients contained high activity to induce FcɛR2/CD23 on CDI4+ monocytes. An increased frequency of FcɛR2/CD23+ monocytes was also observed in rheumatoid arthritis, and sequential studies in patients with systemic lupus erythematosus showed a close relationship between FcɛR2/CD23+ monocytes and disease activity. It is suggested that IL-4 has an important role in the pathogenesis of PSS by activating monocytes, and might also contribute to monocyte activation in other rheumatic diseases.
Failure Co detect deposition of complement and immunoglobulin in allergen-induced late-phase skin reaction in atopic subjects
Authors: FREW A J , KAY A B 
Published: July 2010

SUMMARYThere still remains some controversy regarding the possible role of immune complexes in the pathogenesis of the late-phase skin reaction (LPSR). To assess this, skin biopsies were obtained from LPSR induced in atopic human subjects 6, 24 and 48 h after allergen challenge. Cryostat sections were stained by direct immunofluorescence for the presence of fibrinogen, immunoglobulin classes IgM and IgG and for the the complement components C1q and C3c. Complement components were observed in only two of the 29 biopsies studied. In both instances, only C3c was detected. One of these subjects also had unequivocal IgG staining at 6 h. IgM staining was detected in two out of 10 subjects at 6 h but no significant deposition of immunoglobulins could be found at 24 or 48 h. Fibrinogcn deposition was observed in about half of the biopsies at each time-point. This study suggests that substantial complement and immunoglobulin deposition arc not overt features of the allergen-induced LPSR. although the presence of small amounts of immune complexes, below the sensitivity of the method employed cannot be excluded. Fibrin deposition occurs in the LPSR but docs not appear to be a prerequisite for LPSR development.
Analysis of the cells involved in the lymphoproliferative response toCoxiella burnetiiantigens
Authors: IZZO A A , MARMION B P , HACKSTADT T 
Published: July 2010

SUMMARYVaccination with an inactivated, whole cell, Q fever vaccine (Q-vax) induces lasting antibody conversion and a positive delayed-type hypersensitivity (DTH) skin reaction in about 60% of recipients but a long-lasting positive lymphoproliferative or mitogenic response to C. burnetii antigens with peripheral blood mononuclear cells (PBMC) in 85–95% of subjects. Analysis of the lymphoproliferative response to C. burnetii antigens has now been made by fractionationreconstitution experiments with PBMC from vaccinees, from past infections, and from healthy controls. The major contributor to the response in immune subjects proved to be the T lymphocyte. T cells were stimulated by both the phase I and phase II antigens of two prototype strains of C. burnetii and responses were greatly amplified by addition of IL-2. Similar T lymphocyte stimulation profiles were obtained with the ‘Priscilla’ strain of C. burnetii which represents a different biotype of Coxiella isolated from Q fever endocarditis; Q-vax is therefore likely to protect against endocarditis strains. Fractionation-reconstitution experiments with T and B cells from vaccinees and subjects infected in the past, using various antigenic or haptenic fractions from C. hurnetii indicate that protein, non-lipopolysaccharide components of the organism are responsible for the mitogenic response of immune T cells. However, the role of the lipopolysaccharide in the protective immunogen has still to be defined.
Examination of serum class I antigen in liver-transplanted rats
Authors: SUMIMOTO R , SHINOMIYA T 
Published: July 2010

SUMMARYWe examined the appearance of donor (DA) type class I antigen in the serum of rats that had received isogeneic (DA→DA) or allogencic (DA→PVG, DA→BN, DA→LEW) liver transplants with or without cyclosporin A treatment, using two-site enzyme immunoassay. We also tested the serum titre of class I antigen in the normal DA rats with either 70% hepatectomy or cyclosporin A treatment, in order (o clarify the relationship between the fluctuation in the scrum titre of class I antigen in the recipient and the outcome of the transplanted liver graft. The suppression of liver graft rejection by cyclosporin A treatment significantly lowered the serum level of donor liver-derived class I antigen as compared with that of the recipient without cyclosporin A for a certain period. However, there was almost no correlation between the intensity of rejection of the liver graft and the serum level type class I among these allogencic rejection and non-rejection liver transplantation combinations. The amount of donor-type class I antigen in the recipient’s scrum is dependent on whether the grafted liver is severely damaged following partial hepateetomy, whether the liver has associated biliary complications or ischaemic damage, or whether the liver has had absolute residual parenchymal cell volume or function following liver rejection. Our results suggest that the appearance of donor type class I anligen following liver transplantation is dependent on many factors, and therefore the litre of serum class I antigen may not always be a decisive indicator of liver graft rejection.
Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-6 on the production of immunoreactive IL-1 and TNF-α by human monocytes
Authors: DANIS V A , FRANIC G M , RATHJEN D A , BROOKS P M 
Published: July 2010

SUMMARYThe effects of GM-CSF, IL-2, IFN-γ, TNF-α and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-α by peripheral blood monocytes were studied. Monocytes were cultured for 20 h in suspension and in serum-free conditions which minimized background stimulation of monokine production. GM-CSF, IL-2 and TNF-α directly induced the production of cell-associated IL-1 but little or no IL-1 or TNF-α secretion. Combination of GM-CSF with IFN-γ, IL-2 or TNF-α synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-γ or TNF-α also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergisticaily enhanced TNF-α secretion induced by IFN-γ but not by tipopolysaccharide. GM-CSF did not enhance TNF-α secretion induced by IL-2 or TNF-α. In contrast, IL-2 synergistically enhanced TNF-α secretion induced by IFN-γ. These results are discussed in relation to cytokine involvement in rheumatoid arthritis.
Defective neutrophil and lymphocyte function in leucocyte adhesion deficiency
Authors: LAU Y L , LOW L C K , JONES B M , LAWTON J W M 
Published: July 2010

SUMMARYWe report a Chinese girl with the moderate phenotype of leucocyte adhesion deficiency (LAD), presenting with persistent omphalitis and recurrent soft tissue infections. She had subnormal adhesion-dependent neutrophil functions, such as chemotaxis and chemiluminescence response to a particulate stimulant (opsonised zymosan). Despite her adequate humoral response to documented herpes simplex virus type 1, parainfluenza type 2 and adenovirus infection in vivo. there was marked impairment in the generation of plaque-forming cells (PFC) driven by pokeweed mitogen (PWM) in vitro. IgM PFC were less severely affected than IgG and IgA PFC, probably because IgM production is less dependent on T cell help than IgA and IgG production. The patient’s B cells and accessory cells had reduced function compared with the control subsets, while helper function of her CD4+ cells was virtually absent in the PWM-driven PFC assay. She also had marked defect in natural killer cell activity. The proliferation of her lymphocytes was normal to several plant Iectins, including phytohaemagglutinin, concanavalin A and PWM, but markedly defective to OKT3.
Sequential serological studies of homosexual men with and without HIV infection. Epstein-Barr virus activation preceding and following HIV seroconversion
Authors: SCHATTNER A , HANUKA N , SAROV B , SAROV I , HANDZEL Z , BENTWICH Z 
Published: July 2010

SUMMARYViral cofactors may be important in the pathogenesis of HIV infection and the development of AIDS, but their role is still imperfectly understood. Sequential serological studies were performed in a cohort of 100 homosexual men and 70 matched healthy controls over a mean period of 4 years. Of the patients, 18 were found to be HIV+ on admission to the study and 15 seroconverted to HIV+ during the follow up (seroconversion group). Serum antibodies of both IgG and IgA isotypes against Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were determined. IgG antibodies indicate past infection, while a marked increase in IgG titre or a positive IgA titre were taken to indicate active infection or reactivated latent infection. EBV and CMV infections were about two to four times more prevalent in the homosexual men both HIV– and HIV+, compared with controls. Active infections were increased in the homosexual men and particularly in the HIV+ patients. The seroconversion group revealed activation of both EBV and CMV following HIV infection. When the antibody profile of seroconverting patients at the time preceding seroconversion was compared with a matched group of 39 homosexual men who remained HIV–, no change was found in CMV antibodies, but four out of 15 (26.6%) of the patients had high titres of anti-EBV IgA preceding seroconversion, as compared with only one out of 39 (2.6%) of HIV– homosexual men (/&lt;0.05). This suggests a role for EBV reactivation in the pathogenesis of HIV infection in some patients.
Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis
Authors: D’CRUZ D P , HOUSSIAU F A , RAMIREZ G , BAGULEY E , MCCUTCHEON J , VIANNA J , HAGA H-J , SWANA G T , KHAMASHTA M A , TAYLOR J C , DAVIES D R , HUGHES G R V 
Published: July 2010

SUMMARY
Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84%± 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45%±35.9). Seventy normal human sera had a mean BI of 10%±9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P&lt; 0.001). AECA levels correlated with low complement levels but not with anti-DN A antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.
Anti-IgG antibodies in rheumatic diseases cross-react withStreptococcus mutansSR antigen
Authors: ACKERMANS F , PINI A , WACHSMANN D , SCHOLLER M , OGIER J , KLEIN J-P 
Published: July 2010

SUMMARYWe have previously shown that SR protein, a S. mutans major cell wall protein, as well as the recombinant protein SR (rSR) share common epitopes with human IgG. Since this antigenic mimicry could play a role in the induction of Anti IgG, we have examined, in k-ELISA, the presence of antibodies reacting with S. mutans SR proteins and S. mutans whole cells in sera from 36 patients with rheumatic diseases. The majority of the 36 sera showed a high reactivity with rSR when compared with control sera. Eight highly positive sera were further purified on rSR and human IgG sorbents and tested against both rSR and IgG in ELISA and Western blotting. The affinity-purified antibodies reacted strongly with rSR, IgG and IgG Fab fragments but failed to react with IgG Fc fragment. In Western blotting the addition of unlabelled IgG abolished the reactivity of affinity-purified biotinylatcd antibodies with all antigens, confirming the existence of a common epitopc shared by rSR and human IgG heavy chain. We show the existence in rheumatic diseases of high litres of anti-human IgG antibodies cross-reactive with S. mutans SR proteins. Those antibodies are principally IgG and react with the Fd part of the Fab fragment. We can hypothesize from the above data that this antigenic mimicry existing between S. mutans SR-related antigens and human IgG could play a role in the synthesis of at least a part of the anti-IgG antibodies present in rheumatic diseases sera.
Bacterial lipopolysaccharide enhances deposition of immune complexes and exacerbates nephritis in BXSB lupus-prone mice
Authors: GRANHOLM N A , CAVALLO T 
Published: July 2010

SUMMARYSystemic autoimmune disease is influenced by genetic, immunological, hormonal, and environmental factors. Although environmental factors are major agents that induce or exacerbate autoimmune diseases, the mechanism(s) and the molecular events by which they operate remain poorly understood. Here we used the lupus-prone BXSB mouse as an animal model of systemic autoimmune disease, and we used a bacterial lipopolysaccharide (LPS) as a surrogate infectious agent to gain some insight into the mechanism(s) by which infectious agents exacerbate autoimmune diseases. Our experimental protocol was designed to address three questions: (i) whether spontaneous polyclonal B cell activation (PBA) that occurs in BXSB mice could be further enhanced by bacterial LPS; (ii) whether repeated exposure to LPS would exacerbate autoimmune disease, as reflected by enhanced deposits of immune complexes (ICs) in kidneys and exacerbated nephritis; and (iii) whether the mechanism by which LPS exacerbates nephritis might involve interference with blood cell carrier function, mononuclear phagocyte function, or both. BXSB mice were injected with LPS (25 μg) twice a week for 5 weeks; control autoimmune BXSB mice and immunologically normal (C57BL/6) mice were injected with vehicle only. The three groups of mice were then challenged with soluble ICs to assess the kinetics of their disappearance from the circulation, their uptake by the mononuclear phagocyte system (liver, spleen), their distribution in target organ (kidney), and blood cell carrier function. The results indicate that: (i) spontaneous PBA can be enhanced further by LPS; (ii) exposure to LPS results in increased deposits of endogenous ICs in kidneys and exacerbated nephritis; and (iii) defective handling of ICs by the mononuclear phagocyte system and impaired blood cell carrier function are contributory factors to exacerbated nephritis, but that mechanisms in addition to passive localization of ICs may also be operative.
Effects of IL-5, granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-3 on the survival of human blood eosinophilsin vitro
Authors: TAI P-C , SUN L , SPRY C J F 
Published: July 2010

SUMMARYThe mechanisms that could affect the lifespan of eosinophils after they have left the bone marrow, and their capacity to respond to activation factors were studied by examining the effects of IL-5, GM-CSF and IL-3 on purified human blood eosinophils in culture. All three cytokines prolonged the lifespan of the majority of blood eosinophils. This effect was dose dependent: IL-5 &gt; GM-CSF &gt; IL-3. Light density eosinophils from most patients had a longer lifespan in culture than did normal density eosinophils, with or without the three cytokines. Eosinophil death in the absence of these cytokines occurred by apoptosis. Eosinophils from two patients did not survive when cultured with IL-5, although they survived in the presence of IL-3 or GM-CSF- IL-5, GM-CSF and IL-3 induced the expression of the activation epitope on the eosinophil ribonucleases recognized by monoclonal antibody EG2. We conclude that small amounts of IL-5, GM-CSF and IL-3 prevented programmed cell death in human blood eosinophils and induced the expression of the activation forms of eosinophil ribonucleases. We suggest that differences in the capacity of normal and light density eosinophils to survive in culture, and in the ability of eosinophils from some patients to respond to IL-5 could account for variations in the severity of disease seen in patients with persistent eosinophilia.
IgG human monoclonal anti-DNA autoantibodies from patients with systemic lupus erythematosus
Authors: WINKLER T H , JAHN S , KALDEN J R 
Published: July 2010

SUMMARYWe describe the production of six mouse-human heterohybridomas secreting human IgG anti-dsDN A antibodies derived from patients with systemic lupus erythematosus (SLE). Peripheral blood cells used for fusion experiments were from patients who were shown to have high numbers of anti-DNA secreting B cells in the peripheral blood. All monoclonal antibodies bind to dsDNA in ELISA systems, five are reactive with Crithidia lucilae kinetoplasts and three precipitate dsDNA in the Farr assay. Inhibition studies revealed a remarkable specificity for certain polynucleotide structures. To our knowledge these are the first hybridomas described in the human system that secrete anti-dsDNA antibodies of the IgG class.