摘要:

Circulating parietal cell auto antibodies, a useful diagnostic marker for autoimmune gastritis and pernicious anaemia, are currently routinely tested by serum immune of luorescence reactivity with frozen sections of rodent stomach. The major molecular targets of these parietal cell autoantibodies have recently been demonstrated to be theα- and theβ-subunits of the gastric H+/K+-ATPase (proton pump)1,2. We have demonstrated that tomato lectin binds specifically to theβ-subunit of the proton pump and concomitantly co-purifies theα-subunit34. In the present study, we have exploited the latter observation for the development of a diagnostic ELISA for the detection of parietal cell autoantibodies and compared the performance of this assay with an ELISA using crude gastric membranes. The ELISAs were tested on 72 parietal cell autoantibody-positive sera, 72 parietal cell autoantibody-negative sera and 72 disease-control sera. The ELISA using lectin-purified canine proton pump was superior to that using crude canine gastric membranes in that it was about two-fold more sensitive (82% vs. 43%). With an assay sensitivity of 82% and a specificity of 90%, we propose that the ELISA using the lectin-purified proton pump is a rapid, simple, sensitive and specific diagnostic immunoassay for parietal cell autoantibodies.

ISSN:0891-6934    

DOI:10.3109/08916939209146123

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Pancreatic beta-cell autoantigen recognition by the immune system appears to be a critical event in the evolution of insulin dependent diabetes. Immune recognition involves antigen presentation by macrophages and subsequent antigen-peptide-class II MHC recognition by T cell receptors (TCR). Using the NOD mouse as a model for human IDD, we hypothesized that germline variability in the Dßnodand/or Jßnodsegments could contribute to beta cell autoimmunity by influencing the specific peptides that are recognized. As an initial approach to our hypothesis, we sought to compare these segments to other strains of mice in search of genetic polymorphisms as reported in NZW mice. The germ line TCRßnodgene did not display evidence of an expansion or contraction in the number of Dßnodor Jßnodsegments at the level of resolution provided by restriction fragment length polymorphism analysis. The absence of such polymorphisms suggests thatDßnodor Jßnodsegments are not different from nonautoimmune strains of mice.

ISSN:0891-6934    

DOI:10.3109/08916939209146124

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We report the expression on synovial cells of cell surface molecules known to be involved in T cell activation by antigen presenting cells. Normal human synovial fibroblasts and a human synovial cell line transformed with the SV40 large T antigen were used forin vitrostimulation studies with recombinant cytokines. We demonstrate an increase in MHC-A, B, C expression in normal synovial cells in response to recombinant interferon gamma (r/IFN), tumour necrosis factor alpha and beta (rTNFαandβ) and interleukin-1 (rlL-lα). Intercellular adhesion molecule-1 (ICAM-1) expression was increased in parallel with MHC Class I. The combination of rγlFN and rTNFa was additive in its effect on ICAM-1 expression. Northern blot analysis suggests that ICAM-1 expression in synovial cells is controlled at the level of transcription. In contrast, MHC Class II (HLA-DR) was only significantly induced by rylFN. Other stimuli including interleukin-4 (IL-4), interleukin 6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF) and prostaglandin E2(PGE2) did not affect the expression of ICAM-1 or MHC Class I and II. Leucocyte function antigen 3 (LFA-3) expression was not affected by any of the stimuli tested. Immunoperoxidase staining of rheumatoid synovial tissue confirmed enhanced in vivo expression of ICAM-1 in rheumatoid arthritis. These changes are discussed in the context of T cell activation in inflammatory arthritis.

ISSN:0891-6934    

DOI:10.3109/08916939209146125

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Diabetes susceptibility in non-obese diabetic (NOD) mice may involve immune dysregulation resulting from cytokine deficiencies. The cytokine IL-1 plays a role in various immune as well as endocrine responses and may be hypoexpressed in NOD mice. Treatment with low levels of exogenous IL-1 a for 22 weeks prevented the naturally occurring insulitis and diabetogenic process in NOD mice during and at least 33 weeks after cessation of IL-1αtreatment. Treatment with IL-1αalso inhibited insulitis and hyperglycemia induced by adoptive transfer of pathogenic, polyclonal CD4+8−T cells. Even after islet-cell destruction, IL-1αinjections in diabetic NOD mice normalized plasma glucose levels when administered in combination with insulin, whereas equivalent levels of IL-1αalone did not. Our studies support the hypothesis that IL-1αsuppresses autoimmune diabetes and hyperglycemia in NOD mice by pleiotropic effects on both immune and metabolic systems. Thus, IL-1 treatment could clinically be an effective immunotherapeutic modality for autoimmune diabetes mellitus by suppressing early disease progression or normalize plasma glucose levels when insulin is present.

ISSN:0891-6934    

DOI:10.3109/08916939209146126

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Anti-RNA polymerase I (RPI) antibodies in the sera of MRL/Mp-lpr/lpr and MRL/Mp-+/+ mice, which develop an autoimmune disease similar to human systemic lupus erythematosus, were screened for reactivity with purified RPI or RPI which had been dephosphorylated. In every case (n=10), dephosphorylation of RPI resulted in a significant decrease (33–95%) in antibody binding. The anti-RPI antibodies in the sera of the same mice approximately 6 weeks later also reacted better with untreated as compared to dephosphorylated RPI but, in every case, the decrease in antibody (0–30%) caused by dephosphorylation was substantially diminished. That the proportion of anti-RPI antibodies in the sera of MRL mice decreased with progression of lupus-like disease was confirmed by closely monitoring the antibodies over the course of disease. Anti-RPI antibodies produced at the earliest stages appeared to be directed almost exclusively against phosphorylation-dependent determinants since dephosphorylation of RPI essentially abolished antibody binding. Subsequently, the percentage of the total anti-RPI antibodies in the sera of these mice directed towards phos-phorylation-independent epitopes increased linearly with time. The importance of phosphorylation-dependent epitopes on RPI for the development of the anti-RPI autoimmune response was supported by the observation that treatment of mice with alkaline phosphatase partially attenuated anti-RPI antibody production.

ISSN:0891-6934    

DOI:10.3109/08916939209146127

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Recently we developed a procedure to translocalize one of the extractable nuclear antigens (ENAs), the La protein, to the cell surface of CV-1 cells. Here we report that herpes simplex virus type 1 infection can also induce a translocation of the autoantigen to the cell surface. On the cell surface we detected La protein assembled with large protrusions. Within these protrusions La protein colocalized with virus particles. These protrusions are known to be released from the cell after virus infections. Such complexes consisting of self and virus could provide helper determinants for an anti-self response, and therefore be important in generation of autoimmunity.

ISSN:0891-6934    

DOI:10.3109/08916939209146128

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Experimental autoimmune adrenalitis was produced in mice by immunizing 8 times or more at intervals of 30 days with syngeneic adrenal extract mixed withKlebsiella03 lipopolysaccharide (KO3 LPS) as a potent adjuvant. The cortex regions of the adrenal glands after the 8th injection were definitely infiltrated with polymorphonuclear leukocytes (PMN). The main infiltrates in the lesions after the 9th injection were replaced by mononuclear cells, such as small lymphocytes and macrophages, and further by fibrous connective tissues. There were no histological changes in the medullary regions. The repeated immunization developed the delayed type hypersensitivity to adrenal extract and production of anti-adrenocortical autoantibody in those immunized mice. Moreover, the adrenalitis could be produced in normal mice by transfer of spleen cells from hyperimmunized mice, suggesting the critical role of the cell-mediated immunity. This experimental model might be useful to study immunological phenomena in the pathogenesis of Addison's disease.

ISSN:0891-6934    

DOI:10.3109/08916939209146129

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Myasthenia gravis patients have serum anti-acetylcholine receptor antibodies that compete with monoclonal antibodies for binding to epitopes on the human acetylcholine receptor. To investigate the presence of shared idiotypes we immunised syngeneic mice with each of ten well-characterised monoclonal antibodies, previously raised against purified human acetylcholine receptor, and tested the polyclonal antisera and seven monoclonal anti-idiotype antibodies, for binding to the antigen-combining site, to framework idiotopes, and by ELISA. The polyclonal sera were mostly directed against antigen-combining site idiotopes and cross-reacted only with monoclonal anti-acetylcholine receptor antibodies that bound to the same region on the acetylcholine receptor. In contrast, five of the seven IgM monoclonal anti-idiotypic antibodies raised, none of which demonstrated antigen-combining site specificity in solution, cross-reacted with mAbs binding to more than one region. None of the antisera snowing reactivity with the antigen-combining site inhibited the binding of MG anti-acetylcholine receptor antibody.

ISSN:0891-6934    

DOI:10.3109/08916939209146130

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

This study shows that purified murine monoclonal anti-DNA antibodies and human polyclonal anti-DNA antibodies (from systemic lupus erythematosus—SLE—patients), preincubated with DNA, acquire antihistone reactivity. Conversely, DNAse I treatment of SLE patients' antibodies with anti-histone activity abolishes such activity.It has previously been demonstrated that anti-DNA antibodies bind to the cell membrane and recognize cell-surface polypeptides that have been identified with histones by partial sequencing. In a series of 33 sera from patients with clinically active disease and 29 sera from patients in clinical remission, positivity of an immunoblot analysis detecting antibodies against these polypeptides was associated with clinical activity of SLE (sensitivity, 0.88; specificity, 0.90). Anti-histone reactivity detected by ELISA appeared to be also a good marker of SLE activity (sensitivity, 0.64; specificity, 0.54). As expected, anti-native DNA antibody positivity and lowered complement dosage were also associated with clinical activity (sensitivity, 0.79 and 0.63, respectively; specificity, 0.48 and 0.93, respectively).Since anti-histone reactivity reflects, at least partly, the presence of anti-DNA antibodies complexed to DNA, which could bind to cell-membrane determinants, and is associated with disease clinical activity, it is suggested that this mechanism can contribute to explain the pathogenicity of anti-DNA antibodies.

ISSN:0891-6934    

DOI:10.3109/08916939209146131

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939209146132

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor