摘要:

A panel of autoantigens (myosin, actin, myelin basic protein MBP, and thyroglobulin) was used to analyze antigen recognition by the peripheral blood leukocytes (PBL) of patients with active and stable multiple sclerosis (MS), patients with other neurological diseases (OND) and healthy individuals. The immune responsiveness was studied by examining thein vitrocell proliferation and the increase in the expression of two T-cell-surface activation markers (the interleukin-2 receptor IL-2R, and a late activation antigen recognized by the 19.2 monoclonal antibody). In MS, autoantigen recognition occured more frequently than in the other groups and it was manifested by moderate proliferation or marked elevation of the expression of the IL-2R, whereas autoantigen recognition in the other groups concerned essentially the expression of the late activation antigen. Results similar to those described above were obtained with enriched T lymphocytes either in the presence or absence of IL-2. Our results suggest that the peripheral immune system in MS patients may recognize and can be activated by different autoantigens and not only by MBP, and that this response is quantitatively and qualitatively different from that of PBL from OND patients and healthy individuals.

ISSN:0891-6934    

DOI:10.3109/08916939309014641

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The sera patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) were tested, by ELISA, for antibodies to phosphatidylethanolamine (aPE), as well as to cardiolipin (aCL) and compared to healthy blood donors (HBD). Both, SLE and APS patients presented a higher titre of IgM-aPE antibodies than normals, while the IgG and IgA aPE reactivity did not differ. APS patients were characterized by higher IgM-aPE antibody titres than SLE patients. In contrast, the predominant isotype of aCL antibodies in APS patients was IgG. The IgM aPE reactivity was correlated with IgM aCL reactivity, while no correlation was observed between the total IgM values and IgM-aPE binding units of sera tested. Since it was shown thatβ2-glycoprotein-I (β2-GPI) contributes to a complex antigen by binding to phospholipids and that this antigen is recognized by antiphospholipid antibodies from autoimmune patients, seraβ2-GPI levels were measured and correlated to aCL and APE activity. Although APS patients had higherβ2-GPI levels than SLE patients, no correlation was found between theβ2-GPI levels and IgG/IgM aCL and IgM-aPE reactivities a finding suggesting that in addition toβ2-GPI, other cofactors for aPE antibodies may exist. These findings indicate that aPE and aCL antibodies co-exist and that the IgM-isotype is predominant in APS. In addition, the IgA and IgG aPE antibodies appear to occur in low titres in these patients, as well as in normals and may exist as natural autoantibodies. We suggest that the high IgM-aPE antibodies may be viewed as a thymus independent process.

ISSN:0891-6934    

DOI:10.3109/08916939309014642

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Graves' disease is an autoimmune disorder but the nature of the association between hyperthyroidism and ophthalmopathy is not yet understood. Serum autoantibodies to orbital tissues have previously been identified and the cross-reactivity with orbital and thyroid antigens has been implicated in the development of thyroid-associated ophthalmopathy (TAO). The ophthalmopathy of Graves' disease is remarkable for the hypertrophy of extraocular muscles and proliferation of fibroblasts within the orbit;features which suggest a possible involvement of growth factors. The present study was therefore undertaken to investigate the interaction of IgGs extracted from the sera of patients with Graves' disease, with or without overt ophthalmopathy, with respect to IGF-1 receptor binding sites on fibroblasts from human orbital tissue.IGF-1 binding sites were demonstrated on human orbital fibroblast monolayers grown from eye muscle explants. These cells exhibited a population of high affinity IGF-1 binding sites (Kd, 0.5nM SEM±0.05). IgG prepared from sera taken from patients with Graves' disease (n = 23) significantly inhibited [125I] IGF-1 binding to orbital fibroblasts when compared to IgGs prepared from normal volunteers (n = 13, p<0.002). It was found that 12 of 23 (52%) patients' IgG samples gave rise to significant levels of inhibition of [125I]IGF-1 binding to orbital fibroblasts. The IgG preparations did not bind directly to IGF-1.This study demonstrates that IgG prepared from patients with Graves' disease with or without overt ophthalmopathy interact with IGF-1 binding sites on orbital fibroblasts whereas IgG from normal subjects had no significant effect. This suggests (a) that antibodies may occur in Graves' disease which bind to the IGF-1 receptor and (b) that, if such antibodies were biologically active, IGF-1 mediated pathways may be implicated in the proliferation of orbital fibroblasts and hypertrophy of ocular muscles which characterise TAO.

ISSN:0891-6934    

DOI:10.3109/08916939309014643

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The platelet-activating factor inhibitor BN50730, a hetrazepine, was injected intraperitoneally daily from 30 days of age into diabetes-prone BB rats. While 96% (22123) Tween 80 injected control rats developed diabetes, 0.05 mg/kg BN50730 decreased the frequency to 72% (17/24;n.s.) and 0.5 mg/kg to 56% (14125;p<0.01). Mean onset age in controls was 81±9 days (mean±SD), but BN50730 delayed onset to 87±15 days in the low and 93±12.days (p<0.01) in high dose rats. The relative degree of insulitis was reduced in both low (p<0.01) and high (p<0.05) dose treated groups. Serum insulin in young prediabetic controls decreased from 84±34μU/ml to 38±20 in the 22 rats developing diabetes (p<0.001). Serum insulin in BN50730-protected compared to unprotected rats was 114±49 and 32±22 (p<0.001) in the low, and 91±4 6 and 21±15 (p<0.001)μU/ml in the high dose group, respectively. Increased serum insulin correlated with preserved isletβcells and decreased insulitis. Treatment did not affect thyroiditis. Thus, platelet-activating factor may be involved in insulitis pathogenesis and platelet-activating factor inhibitors may decrease autoimmuneβcell destruction.

ISSN:0891-6934    

DOI:10.3109/08916939309014644

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Interferon-γ(IFN-γ) is a cytokine with multiple activities on a variety of cells. Under various circumstances, IFN-γcan exhibit either pro-inflammatory or inhibitory actions. Treatment of SJL/J mice with a monoclonal antibody (Mab) to IFN-γduring the afferent limb of the immune response to myelin protein produced an enhancement of acute experimental allergic encephalomyelitis (EAE), with increased morbidity, mortality and earlier onset of disease. Systemic administration of IFN-γdid not improve or worsen clinical outcome, but delayed disease onset. Passive transfer of immune lymph node cells co-activated with MBP and anti-IFN-γMab resulted in more severe disease than that induced by MBP stimulated cells or MBP and IFN-γco-stimulated cells. However,in vitroproliferation of an MBP specific T cell line was not influenced by IFN-γnor anti-IFN-γtreatment. Mab to IFN-γinhibited suppressor function, in a non-specific assay. Thesein vivoandin vitroresults suggest that systemic IFN-γserves as a physiological regulator of a suppressor mechanism in EAE. The abrogation of this regulatory mechanism by anti-IFN-γadministration contributes to a more severe form of experimental allergic encephalomyelitis.

ISSN:0891-6934    

DOI:10.3109/08916939309014645

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

It is well known that ageing is associated with various alterations of the lymphoid cell functions. Although both B and T cell are affected, the last appear to be more sensitive to ageing process. During the past years, to gain insight into the mechanism(s) of this impairment, effort has been centered on the helper T cells specifically engaged in the production of interleukin-2 (IL-2) because of the pivotal role played by this cytokine in the activation of several immune functions. The results have demonstrated that the ability to produce IL-2 declines with age. In this paper we report the results of a study performed to determine the influence of age on the capacity to produceγ-interferon (γ-IFN), interleukin-4 (IL-4) and interleukin-6 (IL-6). Mononuclear cells from young and old subjects were assessed for cytokine producing capacity in response to phytohaemoagglutinin stimulation. A significant decrease ofγ-IFN production by old subjects has been observed. No significant difference was instead observed between the old subjects and the young ones as regards IL-4 and IL-6 production. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in elderly, i.e. a normal or increased humoral response in face of a low T cell immune responsiveness.

ISSN:0891-6934    

DOI:10.3109/08916939309014646

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

To determine if glipizide could enhance remission induction in new onset type 1 diabetes compared to intensive insulin treatment alone, 27 patients with type 1 diabetes were intensively treated in an open randomized trial with subcutaneous injections for one month. The insulin was randomly either discontinued (Group A) or the insulin discontinued and glipizide begun (Group B). Three patients in Group A (22%) and 7 in Group B (54%, p<.05) underwent insulin-free remissions for 10.3±4.4 and 8.7±2.6 months, respectively (p = NS). Mean blood glucose levels during insulin treatment were lower in patients entering remissions (94±3 mg/dl versus 102±5 mg/dl, p<0.05). C-peptide levels were performed 0, 4, 8, and 24 weeks after insulin treatment. When all patients were examined, mean stimulated C-peptide levels at 4 weeks (0.58±0.09 pm/ml) were incrreased compared to time 0 (0.32±0.05 pm/ml, p<0.02). Patients not entering remission had higher 4-week stimulated values (0.67±0.12 pm/ml) compared to time 0 values (0.29 + 0.06 pm/ml, p<01), whereas remission patients' mean C-peptide levels remained similar at 0, 4, 8 and 24 weeks. These data indicate that a) insulin treatment plus glipizide induces higher rates of remission compared to intensive insulin treatment alone, b) the intensity of initial metabolic control may be an important determinant for remission induction, and c) endogenous insulin secretion is not associated with remission induction, suggesting that glipizide alters insulin sensitivity or is immunomodulatory in the context of new onset type 1 diabetes.

ISSN:0891-6934    

DOI:10.3109/08916939309014647

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We have previously shown that parietal cell autoantibodies predominantly react with a 60-90 kDa gastric autoantigen1,2, subsequently identified as the (3 subunit of the gastric H+/K+-ATPase (EC 3.6.1.3) (proton pump)3-5whereas Karlsson et al6showed that these autoantibodies primarily target the 95 kDaαsubunit of the pump. In view of these discordant results, we have reassessed the reactivity of parietal cell autoantibodies with the two subunits of the gastric H+/K+-ATPase. We show here that all 26 parietal cell autoantibody-positive sera immunoblot both subunits under appropriate, but mutually exclusive, conditions. Thus, reactivity of anti- parietal cell autoantibodies with the 95 kDaαsubunit is optimal when the SDS-PAGE is carried out with samples which are reduced but not boiled. Whereas reactivity with the 60-90 kDaβsubunit is optimal with samples which are boiled but not reduced. Autoantibody reactivity with theβsubunit is critically dependent on the presence of a full complement of N-linked glycans since partially deglycosylated protein, and recombinantβsubunit expressed in COS cells, bearing high mannose N-glycans, failed to bind to the autoantibody. These studies also suggest that B cell auto-epitopes are located on the lumenal domain of theβsubunit. Reactivity of parietal cell autoantibodies with a bacterial fusion protein incorporating the catalytic cytoplasmic domain of theαsubunit suggests the presence of auto-epitopes in this region of the molecule.

ISSN:0891-6934    

DOI:10.3109/08916939309014648

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Sixteen patients with primary Sjogren's syndrome, verified according to the Copenhagen criteria, were investigated for evidence of complement activation. Thirteen of the patients had intact functional activity of both the classical and alternative pathways, with normal concentrations of the complement proteins Clq, Cls, C3, C4 and the complement protein fragments C2a and C3d in the circulation. In contrast, three patients showed clear evidence of complement activation. Further investigation of these patients revealed manifestations of glomerulonephritis, vasculitis and primary biliary cirrhosis. Six months later, one patient developed a malignant non-Hodgkin lymphoma.We conclude that complement activation is generally not associated with primary Sjögren's syndrome. Evidence of complement activation in patients considered to have primary Sjögren's syndrome should raise the suspicion of concomitant systemic disease and/or extraglandular activity.

ISSN:0891-6934    

DOI:10.3109/08916939309014649

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Treatment of insulin-dependent diabetes remains problematic since there continues to be high rates of morbidity and mortality among affected patients. Good outcomes are most likely to be more common among patients who maintain endogenous insulin reserves for the longest time following diagnosis. The disease process can now be identified in its early, pre-symptomatic stages and thus, the time has come for the investigation of preventive therapies through multicenter clinical trials. A wide variety of strategies are available and their choice should be dependent on the pathogenic stage of disease at which treatment is initiated. This stage-specific approach to prevention is discussed with a particular focus on those therapies that will soon be tested in clinical trials.

ISSN:0891-6934    

DOI:10.3109/08916939309014650

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor