ISSN:0891-6934    

DOI:10.3109/08916939008993380

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Several studies have shown that HLA-B8,DR3 positive subjects may display T cell dysfunctions. Recently, a soluble form of the receptor for IL-2 (sIL-2R) has been demonstrated in human sera and in vitro-stimulat-ed culture supernatants from human T lymphocytes. In the present paper we report sIL-2R serum levels and sIL-2R production from peripheral blood mononuclear cells in HLA-B8,DR3 positive subjects. We found that HLA-B8.DR3 positive subjects have the highest values of serum sIL-2R. but comparing the values of these subjects with those of negative ones no significant difference was observed. As regards the in vitro production of sIL-ZR, no difference exists for unstimulated cultures, whereas after stimulation, the HLA-B8,DR3 positive subjects showed the lowest values compared with negative ones. It is noteworthy that these changes are observed in autoimmune diseases linked to this HLA phenotype.

ISSN:0891-6934    

DOI:10.3109/08916939008993381

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Fifteen women with positive islet cell antibodies were identified in a group of 115 consecutive patients found to have impaired glucose tolerance in pregnancy. These subjects were postulated to be at increased risk of later developing type 1 diabetes mellitus. They were examined post—partum for HLA types known to be associated with this disease and for any increase in Interleukin 2 receptor expression or alteration of T cell subsets of possible relevance to its pathogenesis. Fifteen women negative for islet antibodies and with normal glucose tolerance during previous pregnancy and 15 women with a normal fasting plasma glucose who had never been pregnant were studied as controls.Using flow cytometric techniques a significant increase in both the number and proportion of activated (Interleukin 2 receptor, CD25) lymphocytes in the peripheral blood of women who had islet cell antibodies and previous impaired glucose tolerance in pregnancy was found (0.14±SE 0.03±109/l; 7.1±1.1%) when compared with normal parous controls (0.09±0.01±109/; 4.2±0.6%).p<0.05. Parous controls showed significant increases when compared with nulliparous controls (0.04±0.01±109/1; 2.1±0.2%).p<0.01. No differences were detected between the three groups with respect to total T-lymphocytes (CD3), helper T-lymphocytes (CD4). suppressor/cytotoxic T-lymphocytes (CDE), or the inducer of suppressor (Leu 3+/Leu 8+) subset of T-lymphocytes.Three women persistently islet cell antibody positive, two of whom were HLA DR4, showed impaired glucose tolerance at the time of lymphocyte subset analysis, while two further patients, one DR3 and the other DR4, had developed type 1 (insulin-dependent) diabetes.No correlation between increased Interleukin 2 receptor expression and glucose intolerance was demonstrated. We conclude that islet cell antibody positive women with impaired glucose tolerance during pregnancy are at increased risk of later developing type I diabetes but that heightened immune activation present in these women is in part a post-pregnancy phenomenon.

ISSN:0891-6934    

DOI:10.3109/08916939008993382

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Autoimmune-prone NZB±NZW FI (B/W FI) mice produce a high titer of anti-DNA antibodies.In vivoandin virrostudies showed that in the early life of these mice, the immunoglobulin isotype of these antibodies almost exclusively belongs to IgM class, however, IgG anti-DNA antibodies begin to develop when the mice are about 5–6 months old and the titer exceeds that of IgM antibodies from age 7 months on. We asked whether or not the B cell population responsible for IgM and IgG antibody production belongs to the same lineage. The surface phenotypes of B cell populations responsible for the spontaneous production of either IgM or IgG anti-DNA antibodies were examined using panning and sorting methods with several monoclonal antibodies to B cells, including CD5 (Ly-I) and Lp-3: the latter defines a unique B cell differentiation antigen. We obtained evidence that surface phenotypes of B cells secreting IgM anti-DNA antibodies belong to CD5+Lp-3−- and those of B cells secreting IgG anti-DNA antibodies which occur only in old B/W FI mice belong to CD5−- Lp-3+subpopulations. The majority of peritoneal B cells were CD5+Lp-3+throughout the life span of the mice and anti-DNA antibody production was never evidenced. These findings were discussed in relation to age-associated changes of B cell populations in the spleen of this strain of mice.

ISSN:0891-6934    

DOI:10.3109/08916939008993383

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Recent studies have demonstrated that the Ro/SSA autoantigen is heterogeneous as is the corresponding autoimmune response. In addition the autoimmune response is highly species specific and preferentially reactive with the human antigen. Quantitative ELISA study shows that red blood cell Ro/SSA evolves much more rapidly than lymphocyte Ro/SSA and Western Blot analysis shows that the quantitative ELISA results are mirrored by changes in the 60 kD Ro/SSA molecules but not the 52 kD and 54 kD Ro/SSA molecules. The 52 kD and 54 kD Ro/SAA molecules seem to be relatively conserved as indicated by the Western immunoblotting experiments. These studies add weight to the concept that the antigenic epitopes of these related proteins are under the control of separate genes which have undergone different rates of evolution.

ISSN:0891-6934    

DOI:10.3109/08916939008993384

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Recently, we reported an increased incidence of various autoantibodies in a healthy elderly population (Group A, 64 subjects). Presently we examined whether there is variability in the expression of the age-associated immunological aberrations between different geriatric populations by extending our observations in another healthy elderly population (Group B, 119 subjects). We also determined the serum levels of soluble IL-2 receptors (slL-2R) attempting to define the activation status of the immune system during senescence. Compared to non-elderly controls, healthy elderly individuals exhibited a significantly higher incidence of autoantibodies as well as significantly higher levels of sIL-2R in serum (p<0.001). the latter possibly suggesting the occurrence of lymphocytic activation during the ageing process. The overall prevalence of autoantibodies was statistically associated with the presence of raised sIL-2R levels in serum (p<0.005). These aberrant immunological phenomena were more frequent among the elderly of group A, compared to group B (p<0.005). In contrast to the uniform expression of various autoantibodies previously observed in group A, the autoantibody profile of group B consisted mainly of rheumatoid factor and antibodies to single-stranded DNA. Finally, no association could be demonstrated between the presence of autoantibodies and HLA antigens in 42 elderly studied.

ISSN:0891-6934    

DOI:10.3109/08916939008993385

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Mice with systemic lupus erythematosus (SLE) have unusual patterns of lymphocyte traffic characterised by diminished uptake of intravenously injected autoimmune cells into lymph nodes. This study examines the influence of the lymphocyte micro-environment on this aberrant migratory behaviour.To evaluate lymph node lymphocyte-endothelial interactions which can affect lymphocyte distribution without thein vivoinfluence of liver and spleen, thein vimhigh endothelial venule (HEV) binding assay was used. Lymph node HEV binding of autoimmune MRL-lpr/lpr (MRL/I) and MRL- +/+ (MRL/n) lymphocytes was increased when compared with CBA/T6 lymphocytes and contrasted with diminished lymph node uptake notedin vivo. This was independent of the lymph node source (MRL/I, MRL/n, CBA/T6) onto which the lymphocytes were overlaid. To examine the influence of the microenvironment onin vivotraffic,51Cr-labelled lymph node cells from normal CBA/T6 mice were injected into sex-matched MRL/l, MRL/n and CBA/T6 recipients. The distribution of cells was the same in each recipient strain suggesting that the micro-environment had little influence on the lymphocyte trafficking profiles of autoimmune mice. This study supports the view that aberrant lymphocyte migration in autoimmune mice results from defects intrinsic to the lymphocyte population and not the micro-environment.

ISSN:0891-6934    

DOI:10.3109/08916939008993386

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The effect of disulphide bridges reduction of the microsomal antigen (Mic-Ag) and thyroid peroxidase (TPO) by dithiotreitol (DTT) has been investigated. The reaction of all 67 tested sera from untreated hyperthyroid Graves' and from 22 Hashimoto's patients with high microsomal antibodies (aAb) titer was diminished by 90–95% by DTT, at pH 9.6. The remaining S-10%of the activity was not destroyed by DTT. The residual Mic-Ag after DTT reduction was able to inhibit the binding of all 45 Graves' and 22 Hashimoto's tested aAb's to the native microsomal antigen by 100% at high concentration. Reaction of affinity purified TPO with two monoclonal antibodies (mAb) were diminished by 80% to 95% by DTT pretreatment, while the reaction of one mAb with TPO was only slightly affected. The reaction of TPO and Mic-Ag with rabbit polyclonal anti-TPO serum (rabbit aTPO) was diminished by 60% by DTT pretreatment. The immunological reactivity of TPO with aAb's was diminished by 65% after DTT pretreatment. The microsomal antigen-aAb's complex was not destroyed by DTT. Results presented in this paper suggest conformational epitope structure of the Mic-Ag recognized by aAb's in patients with thyroid autoimmune disease (AITD).

ISSN:0891-6934    

DOI:10.3109/08916939008993387

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Genetic susceptibility is an important issue in understanding the mechanism of the autoimmune endocri-nopathies and in assessing the risk of these conditions in pediatric patients. To this end, we evaluated autoantibodies to thyroid antigens, thyroglobulin (TgA) and microsomal antigen (TMA), in white and in American black juvenile patients with Type I diabetes mellitus (DM) to determine the predictive value of thyroid autoantibodies for the development of autoimmune thyroid disease. Sera from 159 patients (77 black and 82 white) with Type I DM were evaluated. A greater number of whites (41/82 or 50%) than blacks (12/72 or 16%) had thyroid autoantibodies (p<0.01). Fourteen patients (4 black and 10 white) exhibited hypothyroidism, and all had both TgA and TMA. Three patients (all black) had Graves' disease, one of whom had both TgA and TMA. Families of each racial group that had a diabetic child (proband) with thyroid autoantibodies (seropositive) or without thyroid autoantibodies (seronegative) were assessed for TgA and TMA as well as autoimmune thyroid disease. The prevalence of thyroid autoantibodies among siblings of seropositive probands was significantly greater than among the siblings of seronegative probands (p<0.01). The white sibling population showed a closer association of thyroid autoantibody prevalence with increasing age (p<0.05) than the blacks. Significantly more parents of probands than control parents exhibited thyroid autoantibodies (p<0.01). The general pattern of inheritance of either racial group showed that if one or both parents had thyroid autoantibodies, their progeny developed a significantly higher prevalence of thyroid autoantibodies than those of the seronegative parents. While there was no increase in overt thyroid disease among siblings of seropositive probands. a risk of developing autoimmune thyroid disease is probably imparted to these siblings by virtue of the thyroid autoantibodies.

ISSN:0891-6934    

DOI:10.3109/08916939008993388

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

A combination of thymectomy and sublethal irradiation (Tx-X) consistently induced diabetes in female rats of the PVG/c strain. The incidence of diabetes varied from 10.7% to 53.4% in seven successive Tx-X groups (mean 29.7%). Both clinical and subclinical disease was observed with the majority of affected animals developing the former condition. This was acute in onset, rapidly fatal (1–4 days) and characterised by ketosis and lipidaemia. Overtly diabetic rats had markedly raised plasma glucose concentrations compared to normal rats of the same strain and plasma immunoreactive insulin concentrations were comspondingly depressed in this group.Histopathological change within the islets of Langehans correlated with clinical status and ranged from diffuse atrophy in the majority of the acutely diabetic rats to mild and focal lymphocytic insulitis in a proportion of the non-diabetic rats.Islet cell autoantibodies were demonstrated by indirect immunofluorescence in approximately 25% of clinically diabetic animals.The majority of diabetic rats were found to be responsive to insulin and the clinical signs could be reversed by daily parented insulin administration.These observations implicate the immune system in diabetes generation and are consistent with an immune mediated pathogenesis as the underlying cause of the islet cell destruction. This syndrome may thus be a potentially useful animal model for type 1 (insulin dependent) diabetes in man.

ISSN:0891-6934    

DOI:10.3109/08916939008993389

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor