摘要:

Anticardiolipin antibodies (aCL) and HLA-DR antigens were determined in 314 central European patients with systemic lupus erythematosus (SLE). Both HLA-DR4 and DR7 were increased in aCL-positive patients, and aCL were significantly associated with DRw53.The association between DRw53 and aCL was also apparent in those 17 patients with SLE and the anticardiolipin syndrome. There was no association between aCL and HLA-DQ or C4 alleles in SLE.

ISSN:0891-6934    

DOI:10.3109/08916939209001909

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The clinical expression of disease in patients with conditions in which autoimmunity is thought to contribute to the pathogenesis of disease is the result of an unfortunate combination of predisposing and environmental factors. The presence of autoantibodies showing a variety of antigen specificities in sera from many of these patients has been closely correlated with particular spectra of organ involvement or tissue destruction. Their precise role in the disease process is as yet unclear. Sera from patients with paraproteinaemia also often contain autoantibodies to a variety of cell components, although symptoms of autoimune disease are rarely found in this group of individuals. In this study of 42 sera from patients with paraproteinaemia we have confirmed the presence of autoantibodies in 33% (13/42) of samples. Amongst the autoantibodies detected were those to human neutrophils (3), U1RNP (8) and cardiolipin (4). In five sera, the immunoglobulin class of autoantibody did not correlate with that of the monoclonal band. This study extends previous reports of the repertoire of autoantibodies present in sera from patients with paraproteinaemia.

ISSN:0891-6934    

DOI:10.3109/08916939209001910

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Although changes in surface carbohydrate expression of abnormally expanded MRL/Mp-lpr/lpr (MRL/lpr) lymph node (LN) cells have previously been described, the composition and function of glycolipids present on these cells as well as the spectrum of specificity of anti-carbohydrate antibodies reactive with these cells remains obscure. Analysis of antibodies to a panel of 22 carbohydrate structures using a liposome immune lysis assay (LILA) showed that, except for anti-asialo GM2 (GA2) antibodies, marked reduction of antiglycolipid antibody levels was observed in sera from 4-mo-old MRL/lpr mice compared with these from MRL/Mp-+/+ (MRL/+) mice. Absorption experiments revealed that both anti-asialo GM1 (GA1) and globo-side antibodies had binding capacity to MRL/lpr LN cells. To elucidate the glycolipid profiles of MRL/lpr LN cells, glycolipids were extracted from LN cells of both MRL/lpr and MRL/+ mice and analysed. A 30-fold elevation of GM1 was found in MRL/lpr LN cells compared with MRL/+ LN cells. From the results of LILA using GA1/GM1 mixed liposomes, aberrantly expressed GM1 inhibited the classical complement pathway but did not interfere with the binding of anti-GAl antibodies to liposomal GA1. These findings suggest that a drastic GM1 increase on MRL/lpr LN cells would inhibit the action of anti-GAl antibodies and complement on the cell surface. This may explain the escape of these cells from an activated self directed immune response.

ISSN:0891-6934    

DOI:10.3109/08916939209001911

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Nervous tissue expression of immunological signal and recognition molecules, as well as lymphoid tissue immune responses after facial nerve trauma was studied in male rats of the Lewis and Brown Norway (BN) strains. In both rat strains nerve transection caused within four days the appearance of IFN-γ-like immuno-reactivity in the cytoplasm of axotomized motor neurons and an induction of MHC class I and II, and CD4 molecules on surrounding glial cells to a similar extent. T lymphocytes also infiltrated the facial nuclei ipsilateral to the axotomy in all animals. The number of autoreactive T cells in superficial cervical lymph nodes, which in response to whole myelin or peptides of myelin basic protein (MBP) secreted IFN-γincreased markedly after axotomy. This response was more conspicuous in Lewis rats, which are susceptible to experimental allergic encephalomyelitis (EAE), than in BN rats, which are EAE resistant. A proportion of the axotomized Lewis rats also developed widespread perivascular infiltration of mononuclear cells in the CNS, reminiscent of EAE. Hypothetically, a strong expansion of myelin autoreactive IFN-γproducing T cells secondary to nerve trauma may have immunopathological consequences in genetically predisposed individuals. It is also possible that myelin reactive T cells, whether recruited to the lesioned nerve, could have impact on macro-phage function during Wallerian degeneration in the distal stump.

ISSN:0891-6934    

DOI:10.3109/08916939209001912

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Argininosuccinate synthetase (ASS) is a rate-limiting enzyme of urea cycle and functions primarily in the liver, whereas ASS activity is hardly delected in normal lymphocytes. In this study, we examined the level of ASS gene expression in peripheral blood lymphocytes (PBL) from human SLE patients by amplification of reverse-transcribed mRNA using the polymerase chain reaction. We have demonstrated that (a) approximately 40% of SLE patients exhibited 2.5 to 5 times higher expression of ASS gene in PBL than those of healthy PBL and (b) the elevation of ASS gene expression of PBL significantly correlates with the active pathogenesis of SLE patients according to the criteria of Japanese Ministry of Health and Welfare (p<0.001 by student's two-tailedt-test). Thus, it is suggested that ASS gene expression is a promising marker of hyper-activated lymphocytes uniquely generated in patients with systemic autoimmune disease.

ISSN:0891-6934    

DOI:10.3109/08916939209001913

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We used flow cytometry to investigate the binding of platelet-binding IgG (PBIgG) to unfixed platelets in idiopathic thrombocytopenic purpura (ITP), including that of anti-glycoprotein (GP) IIb/IIIa antibodies. Anti-GPIIb/IIIa antibodies were detected in 13/64 ITP patients using antigen-capture ELISA and immunoblotting. When unfixed platelets were incubated with ITP plasma, the PBIgG level was significantly higher than after incubation with normal plasma. When 1μM ADP was added to unfixed platelets, which were incubated with ITP plasma and washed, the PBIgG level increased additively. GMP-140 is a constituent of plateletα-granules, and a monoclonal antibody directed against this protein showed weak binding to platelets after 1μM ADP stimulation. The increase of PBIgG produced by ADP was significantly greater when ITP plasma positive for anti-GPIIb/IIIa antibody was used compared with that obtained using antibody-negative ITP plasma. This increase of PBIgG was markedly inhibited by the removal of extracellular calcium with EDTA or the dissociation of the GPIIb/IIIa complex, by EDTA treatment at 37°C. These results suggest that anti-GPIIb/IIIa autoantibodies are internalized by unfixed ITP platelets and stored somewhere other than theα-granules. This stored antibody pool can be reversibly redistributed on the platelet surface by weak stimulants such as ADP and a functional GPIIb/IIIa complex appears to be necessary for this to occur.

ISSN:0891-6934    

DOI:10.3109/08916939209001914

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Administration of OKT3 anti-CD3 monoclonal antibody (mAb) to patients for transplant rejection, is associated with a distinct and often severe clinical syndrome related to massive cytokine release. Previous reports have similarly demonstrated increased levels of serum tumor necrosis factorα(TNFα) in normal mice following administration of 1452-C11 anti-CD3 mAb. In this study, we compared serum TNFαlevels at baseline and after anti-CD3 stimulation among three groups of mice: normal BALB/c controls, pre-diabetic non-obese diabetic (NOD) mice, and diabetic NOD mice. Baseline serum TNFαlevels, as measured by L929 cell bioassay, were 2×higher in diabetic NOD and 3×higher in pre-diabetic NOD compared with BALB/c. Ninety minutes after anti-CD3 mAb stimulation, serum from BALB/c controls and pre-diabetic NOD contained 2-to 8-fold higher levels of TNF-αas compared to untreated control mice. In contrast, following anti-CD3 mAb, there was a dramatic 20-fold increase in serum TNFαin diabetic NOD mice (levels>5000 pg/ml). Additionally, anti-CD3 mAb increased the steady-state TNFαmRNA transcripts. Spleens from diabetic mice given anti-CD3 mAb had higher steady-state TNFαmRNA than spleen from normal mice similarly treated. The enhanced release of circulating TNFαafter anti-CD3 mAb in diabetic NOD mice was abrogated by pre-treatment of mice with prostaglandin E1(PGE1) 30 min prior to anti-CD3 mAb stimulation. Since dietary lipid can influence cytokine generation, serum from BALB/c mice fed fish (FO) or safflower oil (SO) supplemented diets was examined for TNFαbefore and after administration of anti-CD3 mAb. Mice supplemented with a FO diet had higher serum TNFαlevels at baseline and following anti-CD3 mAB compared with mice fed SO. Supplementation of either lipid resulted in higher serum TNFαlevels than mice fed standard laboratory chow (LC) (4.5% lipid). Taken together, we suggest the enhanced capacity of OKT3 to induce TNFαin patients with IDDM can be diminished by injection of PGE1. In addition, clearly the amount and composition of dietary lipid should be regulated in patients with IDDM receiving anti-CD3 mAb therapy.

ISSN:0891-6934    

DOI:10.3109/08916939209001915

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We have tested sera from patients with autoimmune thyroid disorders with or without ophthalmopathy for immunoreactivity, in a dot blot assay, against a recombinant 98 amino acid fragment of a cloned 64 kDa protein, D1, which is expressed in human eye muscle and thyroid, in the form of a Lac Z fusion protein. Tests were positive in 19 out of 40 patients with established thyroid-associated ophthalmopathy (TAO), in 12 out of 21 patients with Graves' hyperthyroidism (GH) without clinically evident ophthalmopathy, in 5 out of 10 patients with thyroid autoimmunity and lid retraction but no other signs of ophthalmopathy, in 4 out of 23 patients with Hashimoto's thyroiditis (HT) without evident ophthalmopathy and in 2 out of 18 patients with benign adenoma or multinodular goitre, but in only 2 out of 37 normal subjects tested. SDS-polyacrylamide gel electrophoresis and Western blotting for an antibody reactive with a 64 kDa antigen in pig eye muscle membranes was also carried out on sera from patients with TAO and GH. While immunoblotting for antibodies reactive with a 64 kDa protein was more often positive in patients with TAO, in whom 58% had serum antibodies which reacted with a 64 kDa protein, this was not the case in patients with GH without eye signs in whom the prevalence of positive immunoblot tests was 35%. Overall there was a fairly close correlation between the two tests although there were many exceptions. While the apparent discrepancy between antibodies recognizing the human recombinant 98 amino acid peptide in dot blot and those binding to a 64 kDa protein in pig eye muscle membranes in immunoblot could be explained by the existence of more than one epitope on the native protein, it is possible that the peptide D1and the 64 kDa molecule are different. Although the relationship of these antibodies to the ophthalmopathy is uncertain, the high prevalences of antibodies to the D1fusion protein in patients with GH without evident ophthalmopathy (but who may have sub-clinical disease) and in patients with thyroid autoimmunity with lid retraction, which many believe to be an early stage of ophthalmopathy, raises the possibility that these antibodies may be an early marker of the eye disease in patients with thyroid autoimmunity. Further molecular studies will show whether D1and the 64 kDa protein are the same or different molecules while prospective clinical studies of these patient groups will be necessary to determine the significance of the corresponding antibodies.

ISSN:0891-6934    

DOI:10.3109/08916939209001916

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Enzyme-linked immunosorbem assay (ELISA) was used to study the temporal relationship between the appearance of murine autoantibodies reactive to insulin and thyroid membrane antigens (TMA) and the development of diabetes and thyroiditis in the non obese diabetic (NOD) mouse. Overall, 28% of NOD mice had antibodies specific for mouse thyroid membrane antigens (MTMA), 30% had antibodies to human thyroid membrane antigens (HTMA) and 23% of NOD mice had insulin autoantibodies (IAA), in at least one of their serial monthly blood samples. Non autoimmune BALB/c mice did not develop antibodies to these antigens. Presence of IAA was associated with the development of diabetes and in 87% of cases such antibodies were detected before the diabetes was diagnosed. IAA were usually demonstrated before insulitis. No association between thyroiditis and IAA was noted. Anti-MTMA and anti-HTMA antibodies were detected more frequently in NOD mice with thyroiditis than in those without thyroid inflammation. No significant association was noted between detection of serum anti-TMA antibodies and the development of diabetes. In young mice, anti-TMA antibodies were not detected in the absence of thyroiditis. Western blot analysis of NOD sera positive for MTMA by ELISA revealed a heterogeneous pattern of reactivity. The significance of these findings with respect to the pathogenesis of diabetes and thyroiditis and their association, is discussed.

ISSN:0891-6934    

DOI:10.3109/08916939209001917

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Theαandβsubunits of the gastric H+/K+-ATPase (proton pump) have been identified as the major molecular targets of parietal cell autoantibodies associated with pernicious anaemia and with murine experimental autoimmune gastritis (BAG) induced by neonatal thymectomy. Recent studies with BAG suggest that the mechanisms of peripheral tolerance and autoimmunity to extrathymic autoantigens are mediated by subsets of“regulator”and“effector”CD4+T cells, respectively. The persistence of“effector”CD4+autoreactive T cells in the periphery may be a direct consequence of the delayed developmental expression of the target autoantigen. We hypothesize that cytokines produced by the“regulator”T cells prevent the clonal expansion of the“effector”autoreactive T cells, and that neonatal thymectomy induces organ-specific autoimmunity in genetically susceptible individuals by the reduction of the“regulator”T cell population.

ISSN:0891-6934    

DOI:10.3109/08916939209001918

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor