摘要:

We have investigated the number of B-lymphocyte clones secreting anti-ssDNA antibodies in SLE patients and a chronic active hepatitis patient by isoelectric focusing and reverse immunoblotting of serum antibodies. Individual clones can be identified by the unique pattern of bands produced by their antibodies (the clonotype). Using this technique, we have shown that the anti-DNA response of the majority of SLE patients is clonally restricted, in many cases only a single B-cell clone responding. We have also measured qualitative and quantitative changes in expression of B-cell clones and shown that these clones are remarkably stable with lifespans of up to six years or more. These results are in agreement with previous observations of clonal restriction of the anti-DNA response in three mouse models of SLE and in addition show that, unlike the mouse models, human anti-DNA-secreting B-cell clones are extremely stable and long-lived. The implications of these results for models of initiation and regulation of the autoimmune response are discussed.

ISSN:0891-6934    

DOI:10.3109/08916939209148467

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The contribution of carbohydrate residues and peptide chain conformation to autoantibody binding sites on human thyroid peroxidase (TPO) and thyroglobulin (Tg) has been investigated. In addition the nature of carbohydrate residues associated with human TPO has been studied.125I-labelled human TPO and Tg were treated with the following glycosidases: EndoD, EndoH, neuraminidase,O-glycanase, neuraminidase followed byO-glycanase and PNGaseF. Thereafter binding to different sera containing TPO autoantibodies and Tg autoantibodies was assessed using solid phase protein A to separate antibody-bound and free labelled antigens. In addition, labelled Tg and TPO were treated with reducing agent (dithiotreitol) or sodium acetate buffer pH 7.5, 5.5 and 3.2 (followed by neutralisation with 2 M Tris pH 8.3) prior to antibody binding studies. Furthermore, the effect of deglycosylation and treatment with acid buffers on TPO enzyme activity was studied.The nature of carbohydrate residues associated with hTPO was analysed by assessment of the effects of different glycosidases on125I-TPO mobility on SDS-PAGE followed by autoradiography and by the use of lectins.Deglycosylation of labelled Tg and TPO had no clear effect on Tg and TPO autoantibody binding. Reduction of labelled Tg and TPO resulted in almost complete loss of autoantibody binding with all sera studied. Furthermore, adjusting the pH of labelled TPO or Tg transiently to pH 5.5 lowered autoantibody binding in the case of all the sera and the effect was more marked at pH 3.2. TPO enzyme activity (guaiacol assay) of unlabelled TPO was decreased after treatment with EndoH but not with other glycosidases. The low pH buffers affected unlabelled TPO enzyme activity measured by iodide assay.Treatment of125I-labelled TPO with EndoH, neuraminidase and PNGaseF caused marked changes in the double band pattern characteristic of TPO on analysis by SDS gel electrophoresis (TPO doublet). Analysis of changes in the mobility of the 2 bands of the doublet after treatment with different glycosidases and binding studies with lectins indicated that both high mannose and complex type sugar residues were associated with hTPO. The high mannose type residues were associated mostly with the lower band of the hTPO doublet whereas complex type residues were associated mostly with the upper band.Overall, our studies indicate that (1) the major autoantibody binding sites on hTPO and hTg are conformational, (2) sugar residues do not appear to be important in forming the autoantibody binding sites on hTPO and hTg, and (3) both high mannose type and complex type sugar residues are associated with hTPO.

ISSN:0891-6934    

DOI:10.3109/08916939209148468

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The IgG subclass distribution of non-receptor muscle antibodies was examined in 15 myasthenia gravis (MG) sera, employing an indirect haemagglutination-immunofluorescence technique. Four sera contained only IgGl, 4 contained only IgG4 and 7 contained both IgGl and IgG4 muscle antibodies. IgG2 and IgG3 antibodies were not found. Among 11 patients with a defined thymus pathology 8 had thymoma and 3 had thymic atrophy, but there was no correlation between antibody subclass pattern and thymic pathology. Patients with both IgG1 and IgG4 antibodies tended to have the longest disease duration. We conclude that IgG non-receptor muscle antibodies in MG are of the IgG1 and/or IgG4 subclasses, irrespective of thymic pathology.

ISSN:0891-6934    

DOI:10.3109/08916939209148469

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

FI-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe thyroiditis. About 50% of these crosses show circulating autoantibodies to thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated, suggesting that the target organ is not susceptible to autoimmune attack.In the present study we show that despite this mild infiltration TgAAb are only synthesized by lymphoid cells within the thyroid gland. Furthermore, we demonstrate that immunization with chicken thyroglobulin (Tg) in complete Freund's adjuvant causes severe experimental autoimune thyroiditis (EAT) in F1(OSxCB) hybrids.

ISSN:0891-6934    

DOI:10.3109/08916939209148470

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Genetic regulation of the spontaneous anti-histone antibody production in systemic lupus erythematosus (SLE) was studied using the H-2-congenic and T cell receptorβchain gene complex (TCRβ)-congenic NZB and NZW strains and their crosses. We found that the original, parental H-2d/dNZB mice produced significantly higher titers of serum IgM class anti-histone antibodies than did the congenic H-2d/2or H-2Z/ZNZB mice. However, none of these three NZB strains produced IgG antibodies. The NZW strain of any H-2 haplo-type did not produce IgM and IgG anti-histone antibodies. The IgG anti-histone antibodies were produced only by H-2d/Zheterozygous NZBxNZW Fl, but not by homozygous H-2zft or H-2d'd NZBxNZW Fl mice. In studies using (NZBxNZW) FlxNZB backcross mice, only the progeny having both H-2d/zand NZW-type TCRβgenotypes produced high amounts of IgG antibodies. There was a tight linkage between the NZW-type TCRβand the production of IgG anti-histone antibodies in TCR T-congenic NZBxNZW Fl mice. All these findings were in keeping with our preceding observations on the genetic regulation of anti-DNA antibodies in these mice and suggest that certain common mechanisms such as superantigen-mediated or common idiotope-mediated regulations may underlie the production of these two distinct autoantibodies in NZBxNZW Fl mice.

ISSN:0891-6934    

DOI:10.3109/08916939209148471

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

MRL/Mp-lpr/lpr mice develop massive lymphadenopathy characterized by expansion of an unusual population of T cells with the Thy 1+, CD3+, CD4-, CD8-(double negative) phenotype. The role these cells play in accelerating the autoimmune syndrome seen in these mice is unknown. In order to better understand the origin of the expanded population of T cells, we have derived a panel hybridomas from double negativeIprlymph node cells. Surprisingly, eleven of twelve hybridomas selected for the absence of surface CD4 and CD8 do not express CD3. Six of eleven confirmed to have inherited the MRL T cell receptor locus have rearrangement at that locus, suggesting commitment to a T cell lineage. Only hybridoma 2.4, which expresses CD3, responds to ConA, anti-CD3 monoclonal antibody, and induces antibody production. The presence of CD3-, CD4-, CD8-T cells in the periphery ofIprmice confirms aberrant T cell development in these mice and suggests an intrinsic cell defect which is expressed early in lymphopoiesis.

ISSN:0891-6934    

DOI:10.3109/08916939209148472

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939209148473

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939209148474

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor