摘要:

Five separate monoclonal antibodies (MoAbs) to human thyroid peroxidase (hTPO) were raised by immunising Balb/c mice with hTPO purified from detergent solubilised thyroid microsomes by high performance liquid chromatography (HPLC). The epitope specificities of these MoAbs were determined by assessing their ability to bind to purified recombinant fusion protein fragments of human TPO (TPO(r)) generated inE. coli. A total of seven small overlapping fragments (averaging 104 amino acid residues) of hTPO, encompassing over 90% of the extracellular region of the molecule, were generated as glutathione S-transferase (GST) fusion proteins. The sequential epitopes on TPO(r) recognised by these MoAbs were analysed by both immu-noblotting and enzyme linked immunosorbent assay (ELISA). Two different MoAbs (A4 and A5) recognised sequential epitopes within the TPO(r) preparation termed Rla+b (residues 1-160) and more specifically, in the case of MoAb A4, within the subfragment Rib (residues 70-160). The inability of the other MoAbs (A1-A3) to recognise recombinant fragments, suggests they either recognise conformational determinants on the TPO molecule or epitopes that are present on the small regions of the TPO molecule which have not been expressed as recombinant proteins.

ISSN:0891-6934    

DOI:10.3109/08916939209035148

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

C57BL/6 mice (B6) which are homozygous at thenu (nude, athymic) andIpr(lymphoproliferation) locus (B6nulpr)are short-lived. We showed previously that increased survival could be obtained by grafting lymphoid cells from euthymic /pr-homozygous B6 mice (B6Ipr)mice ([Ipr→nulpr] chimaeras), but curiously enough not from normal (B6wild)mice ([wild→nulpr] chimaeras). Moreover female, but not male, [Ipr→tnulpr] chimaeras developed spleen and lymph node enlargement. In the present paper the distribution and absolute concentrations of all serum immunoglobulin (Ig) isotypes have been determined in these chimaeras and their controls. All chimaeras displayed whole serum Ig levels higher than those of B6wildmice, suggesting a successful reconstitution of the athymic recipients by the grafted lymphoid cells, but two types of chimaeras were peculiar. The short-lived [wild→nulpr] chimaeras showed a proportion of IgM as high as ungrafted B6nulprmice, suggesting a deficient down-regulation of IgM production by the grafted B6wild-typelymphoid cells. The [Ipr→tnulpr] female chimaeras recovered a long lasting overexpression of all Ig isotypes, like B6Iprmice, while all the other chimaeras showed a transient overexpression only. Since neither lymphadeno-pathy nor persistent increase of serum Ig levels were observed in [Ipr→nu] chimaeras, our data confirmed the need for a geneticallyIprhost to allow the significant development of theIprsyndrome.

ISSN:0891-6934    

DOI:10.3109/08916939209035149

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Three groups of thymectomized patients with myasthenia gravis (MG) were selected for study, 16 with thymoma, 16 with thymic atrophy and 32 with follicular hyperplasia of the thymus. All 16 patients with thymoma, 15/16 with thymus atrophy and 30/32 with follicular hyperplasia had AChR antibodies. Non-receptor muscle (CA) antibodies were found in sera of 15/16 patients with thymoma, 3/16 with thymus atrophy and in none of the sera from patients with follicular hyperplasia. There were 2 patients with thymoma and polymyositis, but none of the thymoma patients had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or other autoimmune disorders. Among the 32 patients with follicular hyperplasia of the thymus were 2 with SLE, 2 with RA and 1 with juvenile diabetes mellitus.In this study, there was an increased incidence of non-muscle autoimmune disorders among MG patients with follicular hyperplasia of the thymus but not among MG patients with thymoma.

ISSN:0891-6934    

DOI:10.3109/08916939209035150

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

In addition to its well known effects on reproductive organs and lactation the pituitary hormone prolactin (PRL) also influences immune functions. The present investigation was performed in order to clarify the regulatory role of prolactin in autoimmune disease by using the collagen II arthritis model. Groups of virgin female DBA/1 mice were subjected to different short-term treatment protocols (5-10 days) with rat PRL and the drugs bromocriptine (inhibits prolactine secretion) and haloperidol (enhances prolactin secretion). Treatments were performed at different stages of disease development, and effects on clinical scores, anti-collagen II antibody titres as well as agalactosyl IgG levels were recorded. The effects of the treatment protocols on serum PRL levels were assessed by using a radioimmunoassay (RIA) system. Although the accumulated results of the present study indicate that PRL does not fulfil a major role in the regulation of collagen II arthritis, some interesting observations were made. High levels of PRL (PRL injections) made the arthritis worse only if treatment was performed during the induction stage of the disease. Bromocriptine treatment during the immunisation period did not significantly affect the course of arthritis, but treatment at later stages tended to cause exacerbation (significant at the onset period only). These results indicate that PRL has different effects during early and late stages of the development of collagen 11-induced arthritis.

ISSN:0891-6934    

DOI:10.3109/08916939209035151

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We have recently described a human IgM monoclonal antibody (mAb), reactive with both self antigens, i.e., cytoskeleton filaments and smooth muscle, and Epstein-Barr virus (EBV)-induced nuclear antigen (EBNA), produced by EBV-transformed B lymphocytes isolated from a patient with infectious mononucleosis (IM).In order to achieve higher antibody secretion in culture supernatant, the mAb-producer cells were fused with ouabain-resistant mouse myeloma cells and a stable human-mouse heterohybrid, coded HY 5488, producing up to 80 //g/ml IgM mAb, was isolated after 4 cloning procedures. Purified HY 5844 mAb was used to immunize mice for the production of a murine anti-idiotypic mAb, which was used to probe the expression of the idiotope of HY 5488 mAb (Id 5488) in sera of IM patients and normal controls by ELISA.It was found that Id 5488 is expressed both in IM patients and normal controls, and that Id 5488 expression is significantly higher in IM patients' sera; furthermore, in IM sera a statistically significant correlation between Id 5488 expression and anti-cytoskeleton and anti-smooth muscle autoantibodies was found.It is suggested that at least part of EBV-induced IgM autoantibodies appearing during IM are secreted by B lymphocytes programmed to the production of“natural antibodies”bearing Id 5488-like idiotopes.

ISSN:0891-6934    

DOI:10.3109/08916939209035152

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The presence of autoantibodies (aAbs) to thyroglobulin (TG) and thyroperoxidase (TPO) in most of the patients with autoimmune thyroid disease is now well documented. Studies of these aAbs suggested that some, termed TGPO aAbs, could interact with both TG and TPO. This hypothesis was investigated using IgG fraction from a pool of 25 patients' sera with high TG and TPO aAb titres. Immunopurification of TG, TPO and TGPO aAbs was carried out by sequential affinity chromatography using a large quantity of highly purified human TG and TPO. TGPO aAbs, obtained by adsorption-elution of affinity purified TG aAbs onto a TPO column, were found to represent about 20% of the TG reactive aAbs and 0.23% of the total amount of IgG. Purified TGPO aAbs were characterized and compared to specific TG and TPO aAbs. In contrast to TG and TPO aAbs which recognized only their target antigen, TGPO aAbs showed high affinity interactions with both TG and TPO. As compared to TG aAbs, TGPO aAbs displayed similar affinity for native TG and higher affinity for denatured TG. Compared to TPO aAbs, TGPO aAbs showed lower affinity for both native and denatured TPO. TGPO aAbs also differed from specific TG and TPO aAbs with regard to IgG subclass distribution and antigen fine specificites as determined by monoclonal antibody assisted mapping of TG and TPO surface epitopes. Taken together, these data indicate that TGPO aAbs are effectively present in the serum of patients with autoimmune thyroid disease. TGPO aAbs may be considered as a subpopulation of TG aAbs with the unique property to cross-react with TPO. The existence of aAbs cross-reacting with these functionally and antigenically related thyroid molecules could lead to a re-examination of the emergence of thyroid autoimmunity.

ISSN:0891-6934    

DOI:10.3109/08916939209035153

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939209035154

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with different forms ofboth primary and secondaryvasculitis and glomerulonephritis. These antibodies are directed against different enzymes located in granulocyte granules. In this review ANCA-related antigens and solid phase assays for ANCA detection will be discussed. Furthermore, we will address the clinical relevance of ANCA and will deliberate on their possible pathogenic implications.

ISSN:0891-6934    

DOI:10.3109/08916939209035155

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Understanding of myasthenia gravis (MG) has been advanced by a series of clinical and basic breakthroughs since the early recognition that it mimics curare poisoning and can likewise be treated with anti-cholinesterase drugs1, which established that it is a defect in nerve-muscle transmission. The subsequent identification2of high affinityα-neurotoxin probes led to efforts to purify and characterise their targets-the nicotinic acetylcholine receptors (AChR)-initially from detergent extracts of the AChR-rich electric organs of the electric ray (Torpedo). When the resulting product was used to immunise rabbits, they developed typical myasthenic signs that were also cleared by anti-cholinesterases3. This was dramatic support for Simpson's earlier prediction4that MG would prove to be autoimmune, and was rapidly confirmed by the ready detectability of autoantibodies to human muscle AChR in 85590% of MG patients5. In the 1980s, theTorpedo, human and other AChR genes have been cloned and sequenced6, and so, for over a decade, MG has been one of the best defined autoimmune diseases. We are thus in a phase of consolidation, with several groups focusing on how the antibodies cause AChR loss, on the immunogenetics and cellular immunology of MG patients, on the possible involvement of the thymus in initiating the response and on the AChR-specific T cells that are widely believed to be crucial for its induction. Most groups are striving towards the ultimate goal of selectively extinguishing a specific autoantibody response7

ISSN:0891-6934    

DOI:10.3109/08916939209035156

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939209035157

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor