摘要:

Autoepitope and DNA-binding domain on a histone H1 molecule were compared using truncated histone H1 peptides as antigens. At least two epitopes (epitope A, N-terminal side; epitope B, C-terminal side) were found both of which were composed of∼20 amino acids. IgM from all 17 anti-histone H1-positive SLE sera reacted with epitope A. IgG from 12 sera reacted with epitope A and IgG from 4 sera reacted with epitope B. In one case, no IgG anti-histone H1 reactivities were found while IgM from the same patient reacted with epitope A. Epitope A had the ability to bind DNA. The reactivities against histone H1 of affinity-purified anti-epitope A autoantibodies were inhibited by DNA. These data suggest that some anti-histone H1 antibodies are directed against a histone H1 DNA-binding site, raising the possibility that an idiotype/anti-idiotype network, at least in part, is involved in the generation of anti-histone H1 autoantibodies.

ISSN:0891-6934    

DOI:10.3109/08916939209112333

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Polyclonal antibodies were raised against the individual 85 and 70 kDa subunits of the Ku complex purified from nuclear extract prepared from the T cell line MLA 144. They specifically recognise the appropriate subunits of the Ku complex from whole cell extract of HeLa cells using Western blot analysis. They are also able to identify the Ku proteins present in the cell membrane using FACS analysis.

ISSN:0891-6934    

DOI:10.3109/08916939209112334

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

According to recent evidence, the presence of an Arg residue at position 52 in the HLA-DQ alpha chain may confer susceptibility to Type 1 diabetes and thus be possibly used to define quantitatively the genetic risk of this disease. Arg52 and non-Arg52 DQA1 alleles cannot be typed by the conventional cytotoxicity test and they must be distinguished at the genomic level. We describe a simple procedure which discriminates the DQA1 alleles based on the differential electrophoretic migration of the DNA heteroduplexes they form with a reference DNA fragment. A major advantage of this procedure is the fact that no hybridization probe is required. Practically, this typing procedure consists of an electrophoretic run of the products of a selective PCR in polyacrylamide gel.

ISSN:0891-6934    

DOI:10.3109/08916939209112335

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Polyamines—putrescine, spermidine, and spermine—are a group of positively charged organic molecules that are present in all living cells. They are important regulators of cell growth and differentiation, but the precise mechanism of their action is not known. Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines. Recent studies demonstrated that down-regulation of polyamine biosynthesis by irreversible inhibition of ODC with difluoromethylornithine (DFMO) is a novel therapeutic approach for the treatment of murine lupus in autoimmuneMRL-lpr/lprmice. Since murine lupus in this strain is associated with a major alteration in thymic T cell subopulations, we questioned whether abnormal polyamine biosynthesis contributes to aberrant T cell maturation in the thymus ofMRL-lpr/lprmice. Thymocytes were analyzed for cell surface markers, CD4 and CDS by 2-color flow cytometry using their respective monoclonal antibodies. The proportion of thymocyte subsets in disease-free mice (8–10 week of age) was∼72% double positive (DP; CD4+CD8+) cells, 5–7% double negative (DN; CD4-CD8-) cells, 11–16% CD4+ cells and 7–8% CD8+ cells. At 14 weeks of age, a stage of clinical disease expression, thymocytes were marked by the presence of∼40% DN cells and∼25% DP cells. The percentage of T cell subsets in untreated (-) and DFMO-treated (+) mice at 14 weeks were as follows: CD4-CD8-, 40113 (-) versus 19±4* (+); CD4+CD8+, 25+14 (-) versus 47±10* (+); CD4+, 24±3 versus 17±5 (+); CD8+, 8.7±2.1 (-) versus 14+3.5* (+) (*P<0.05; n= 4.6). High levels of immunoreactive ODC protein was detected at this age using flow cytometry with anti- ODC antibody. HPLC analysis showed a 2-fold increase in intracellular putrescine and spermidine levels in thymocytes of 14-week oldMRL-lpr/lprmice compared to those of 10-week old mice. ODC activity and polyamine levels were significantly lower in DFMO-treated mice than that of untreated controls. HPLC analysis further showed that DFMO downregulated polyamine biosynthesis. These results demonstrate a major role for polyamines in the development of CD4 and CD8 expression and the functional maturation of T cells. Polyamine-induced alterations in T cell development appear to contribute to autoimmune disease inMRL-lpr/lprmice since polyamine depletion with DFMO-treatment prolonged their life-span and prevented renal injury.

ISSN:0891-6934    

DOI:10.3109/08916939209112336

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Blood cells from patients with systemic lupus erythematosus (SLE) showed a raised level of spontaneous IgG production that included antibodies to DNA and to common environmental antigens (influenza virus haemag-glutinin, adenovirus hexon and mannan fromCandida albicans). In contrast, no IgG antibody was produced against an antigen not normally encountered in the UK (egg antigen fromSchistosoma mansoni) or a self-antigen not generally associated with SLE (thyroglobulin). IgM production was raised to a lesser extent and only antibodies to DNA were detected. When normal cells were stimulated with pokeweed mitogen orS. aureusorganisms, the specificity pattern of IgG production was similar to that described above for SLE with the major exception of the absence of IgG anti-DNA. IgM antibodies to DNA and all the other antigens were detected, but the specificity of the IgM ELISA assays for the protein antigens needs further clarification. The activity of IgM anti-DNA relative to total IgM was far greater in the SLE system. These results provide further evidence that a response to self-antigen is required for production of pathogenic IgG autoantibodies in SLE.

ISSN:0891-6934    

DOI:10.3109/08916939209112337

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Anti-DNA and anti-DNA polymerase I (RPI) autoantibody responses are symptoms of systemic lupus ery-thematosus (SLE). To investigate the relationship between these antibodies (Ab), rabbits were immunized with one of the following preparations: human SLE anti-DNA Ab; human SLE anti-DNA IgG; normal human anti-DNA Ab; human Grave's disease anti-DNA Ab; murine SLE anti-DNA Ab or anti-DNA IgG Fab; various normal human, murine, or rabbit IgG preparations; or complete Freund's adjuvant (CFA), alone. All of the animals immunized with anti-DNA Ab (n=14) generated Ab reactive in radioimmunoassay with: ssDNA, dsDNA, RPI, the soluble fraction of rabbit liver crude nuclear extract, and the immunogen. Induced rabbit anti-DNA Ab in turn induced these responses in a different rabbit: a rabbit immunized with rabbit anti-DNA IgG Ab which had been previously induced by immunization with human anti-DNA Ab, produced Ab reactive with ssDNA, dsDNA, RPI, and the soluble fraction of rabbit liver nuclear extract. Although an individual animal's antisera reacted consistently over the course of immunization with the same individual RPI subunit(s), antisera from different animals reacted with different subunits of the 9-subunit RPI complex in Western blot analyses: 190kD (n=6); 120kD (n=1); 62 kD (n=4); 45 kD (n=2); and, no reactivity (n=2). In contrast, animals immunized with normal IgG or CFA produced responses only against the immunogen. Together, these data suggest that anti-DNA and anti-RPI responses are connected through an autoimmune network in SLE.

ISSN:0891-6934    

DOI:10.3109/08916939209112338

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The eyes and pineal glands from 10 monkeys immunized with S-antigen were studied using routine histo-pathological and immunohistochemical techniques. Seven out of 10 animals developed uveitis between 19 and 33 days after the initial immunization. Histopathology of the eyes harvested 70 days after immunization showed moderate to marked uveoretinitis, subretinal fibrosis, retinal necrosis and gliosis. The pineal glands demonstrated chronic pinealitis. The infiltrating cells were both CD3 and CD19/CD22 lymphocytes with a ratio of 1.4 in the eye and 2.2 in the pineal gland. The ratio of CD4 to CD8 lymphocytes was 1.5:1. MHC Class II antigens and adhesion molecule (ICAM-1) were observed on resident cells. The influx of B lymphocytes and the formation of subretinal fibrosis differentiate the disease in the monkey from that in the rat and mouse. These findings are similar to Vogt-Koyanagi-Harada syndrome and subretinal fibrosis with uveitis syndrome in human.

ISSN:0891-6934    

DOI:10.3109/08916939209112339

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Chronic autoimmune thrombocytopenic purpura (ATP) is a common autoimmune-mediated bleeding disease in which autoantibodies are directed against platelets, resulting in their enhanced Fc-mediated destruction by macrophages in the spleen. While there has been extensive studies relating to the autoantibodies in this autoimmune disorder, relatively few have dealt with cell-mediated immunoregulation of the anti-platelet autoanti-body response. Nonetheless, there is accumulating evidence that suggests the production of these anti-platelet autoantibodies is under the influence of several abnormal lymphocyte-mediated mechanisms, i.e. enhanced anti-platelet T helper cell activity with concomitant reduced T suppressor cell activity. This review focuses on these cellular events and presents a working model which attempts to explain their close interrelationships.

ISSN:0891-6934    

DOI:10.3109/08916939209112340

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939209112341

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Joint swelling and tenderness in rheumatoid arthritis (RA) probably result from IgG aggregates activating complement with the consequent attraction of polymorphonuclear leucocytes (PMNs) and the liberation of their granule enzymes such as kininogenases. By contrast IL-1 and TNF are the major stimulants of cartilage and bone loss although other agents contribute. The fundamental drive for the production of these mediators is unknown but a role for heat shock proteins is suggested from work on pristane induced arthritis.

ISSN:0891-6934    

DOI:10.3109/08916939209112342

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor