摘要:

The nature of the putative autoantigen in Graves' ophthalmopathy (Go) remains an enigma but the sequence similarity between thyroglobulin (Tg) and acetylcholinesterase (ACHE) provides a rationale for epitopes which are common to the thyroid gland and the eye orbit.In an attempt to define the shared epitope, we have screened aγgt 11 human thyroid cDNA library using a polyclonal antibody to Torpedo ACHE and isolated two clones, which upon sequencing, were shown to contain Tg segments, corresponding to portions of the C terminal part of the molecule which has a high similarity with ACHE.Having demonstrated the existence of an epitope common to Tg and ACHE, the clones have been further tested and found to be positive in lysis plaque assays with 1/10 sera from patients with Hashimoto's thyroiditis (HT), 8/8 from patients with Graves' ophthalmopathy and 0/8 normal sera.We have investigated the physiological significance of this common epitope by in situ immunolocalization studies in which the polyclonal antibody to Torpedo ACHE (which was used for screening the library) and immunoglobulins (Igs) from 6 Go patients tested were shown to bind to end plate regions of human foetal muscle fibres which were concurrently shown to be rich in cholinesterase activity; Igs from 3 normal individuals and 2 patients with Hashimoto's thyroiditis did not bind.The results demonstrate and characterize an epitope which is common to Tg and ACHE and show that Go patients Igs contain antibodies which bind to muscle end plates rich in cholinesterase. The significance of these findings to the pathogenesis of Go is discussed.

ISSN:0891-6934    

DOI:10.3109/08916938909099014

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Experimental autoimmune uveitis (EAU) was observed in Hartley guinea pigs following immuunization with high doses (200μg) of four synthetic peptides designated peptide 3, K. N and M which correspond to amino acid positions 221–240, 241–260. 281–302, and 303 to 320 respectively in bovine S-antigen. Histopathologically, a moderate inflammatory response involving the uveal tract and retina was observed using peptide N and peptide M as immunogens, whereas peptide 3 and peptide K. caused only a mild inflammatory response with very few inflammatory cells in the retina. In contrast, animals with EAU showed an associated pinealitis (EAP) characterized by an extensive lymphocytic infiltration of the central and subcapsular areas of the pineal gland. Lymph node cells of guinea pigs immunized with peptide 3. peptide K, peptide N or peptide M showed strongin vitroproliferative responses against the respective immunizing peptide as measured by [3H] thymidine uptake. The results suggest that under appropriate experimental conditions S-antigen may contain multiple pathogenic sites. The relevance of these studies in the pathogenesis of EAU is discussed.

ISSN:0891-6934    

DOI:10.3109/08916938909099015

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

In this study we report the spontaneous production of autoimmune anti-thyroglobulin antibodies (Tg Ab) by peripheral blood lymphocytes from patients with autoimmune thyroid disease and the use of these cells to study the regulation of this productionin vitro. Using a mitogen free microculture system we have found a significant correlation between an individuals' serum titre and the amount of Tg Ab producedin vitro. At low B: T cell ratios Tg Ab production decreased. Specific depletion of suppressor T cells and helper T cells was accomplished using the monoclonal antibodies OKT 8 and OKT 4 respectively. Suppressor cell depletions resulted in increases in Tg Ab production while depletion of helper cells had no consistent effect. The addition of pokeweed mitogen had no stimulatory effect on spontaneous thyroglobulin antibody production. In contrast, when T cell conditioned media was added to the cells, Tg Ab production increased substantially in all patient cultures tested but not in normal control cultures.The results of this study are consistent with the existence of functional thyroid-antigen specific suppressor cells in the peripheral blood which are actively involved in the regulation of autoantibody producing B cells. The results obtained with the cultures maintained in conditioned media show that autoimmune lymphocytes are extremely sensitive to one or more stimulatory factors present in the media and suggests an important role for the production of soluble lymphocyte factors and the expression of receptors for these factors in the aetiology of autoimmune thyroid disease.

ISSN:0891-6934    

DOI:10.3109/08916938909099016

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

While much evidence appears to support the hypothesis of AIDS being an autoimmune disease, equally impressive facts negate the theory. At most, one can presently speak only of the“autoimmune features”of this very complex syndrome AIDS most strikingly presents with various autoantibodies including those directed against both red and white blood cells. These antibodies appear to be—at least in part—responsible for some of the autoimmune features of the disease. Several clinical and serological similarities exist between AIDS and the“classic”autoimmune disease SLE. In fact, following the isolation of HIV, researchers once again began searching for a viral etiology of SLE. It appears that while autoimmune mechanisms may explain some of the clinical and serologic manifestations of the disease, not enough evidence exists as yet to decidedly point either for or against its classification as an autoimmune disease.

ISSN:0891-6934    

DOI:10.3109/08916938909099017

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916938909099018

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916938909099019

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916938909099020

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916938909099021

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor