摘要:

We have used the MRL/lprmurine model of spontaneous lupus to investigate three questions in infection immunity: (1) does mycobacterial infection have any effect on the mortality of the autoimmunity-pronelprmice?; (2) does the infection modify the progression of kidney disease oflprlupus?; and (3) does thelprgene change the resistance of mice to mycobacteria? Experimental infections were induced by intraperitoneal inoculation of 107viable bacilli ofMycobacterium aviumin 3 months old MRL/lprmice and also in congeneic MRL/+ mice (lacking thelprgene). MRL mice were sacrificed 1, 2.5 and 4 months after theM. aviuminjection. We found that infection caused lowering of urine protein concentration inlprmice as compared with age-matchedlprcontrols. Mycobacteriosis also induced a marked decrease in the mortality oflpranimals, e.g. 85% of infectedlprmice reached the age of 7 months whereas only 10% of controllprmice reached the same age. MKL/lprmice showed, after 1 and 2.5 months of infection, higher mycobacterial loads than the congeneicnon-lprMRL mice; after 4 months of infection, however, differences inM. aviumloads between the two groups of MRL mice became not statistically significant. We conclude that: (1) mycobacterial infection increases the life span oflprmice; (2) the infection slows down the progression of kidney disease in the lupus-pronelpranimals; (3) the autoimmunity genelpris associated with a transient decrease in host resistance to mycobacteria.

ISSN:0891-6934    

DOI:10.3109/08916939308993323

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We examined c-sis, c-myc, and c-mybproto-oncogene expression in fibroblasts cultured from affected and unaffected skin of patients with systemic sclerosis (SSc), and from healthy donor skin. Total cellular RNA from cultured dermal fibroblasts was used in slot blot analysis and scanning densitometry or phosphorimaging to quantify steady-state levels of proto-oncogene mRNAs. PDGF B-chain levels in culture supematants of fibroblasts were determined by ELISA. Our results demonstrate that steady-state levels of c-mycand c-mybmRNA were elevated 1.5-to 5.6-fold in intralesional fibroblasts from SSc patients as compared to other cells examined. Levels of c-sismRNA and PDGF-B protein were comparable regardless of source. Elevated c-mycand c-mybexpression may be indicative of, and may contribute to, fibroblast activation in SSc.

ISSN:0891-6934    

DOI:10.3109/08916939308993324

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Sera of patients with Addison's disease contain autoantibodies recognizing antigen(s) in the adrenal cortex. In the present study we have examined the antigen expression in normal (n = 6) and pathological human adrenal tissues (n = 24) and also in the human steroid-producing adrenocortical cell line NCI-H295. Sera from two patients with Addison's disease were selected as they strongly stained the human adrenal gland and identified a 54 kDa autoantigen previously demonstrated as 21-hydroxylase. These sera reacted with normal human adrental cortex (n = 6), all hyperplasias (n = 5) and all the adrenocortical cancers (n = 9), whereas slight or no reactivity was observed in the adenomas without any detectable excess of peripheral steroids (n = 4). Both patient sera reacted in an identical manner with each tissue specimen and they also reacted strongly with the steroid-producing cell line. The data demonstrate that the expression of the Addisonian autoantigen correlates with the functional activity of adrenocortical neoplasms. Furthermore they suggest, that immunohistochemical stainings for steroid-producing enzymes may be clinically useful in the characterization of adrenal lesions.

ISSN:0891-6934    

DOI:10.3109/08916939308993325

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Insulin-dependent diabetes mellitus (IDDM) is associated with the formation of autoantibodies against different antigens in the islets of Langerhans, so-called islet cell antibodies (ICA). The expression of a major autoantigen, the beta-cell specific enzyme glutamic acid decarboxylase (GAD), is glucose-dependentin vitroand correlated to insulin releasein vitro.In this study the expression of islet autoantigens was examinedin vivoand the relationship between beta-cell function and islet cell surface antibody (ICSA) reactivity was tested.Rats were fed for 10 days with glipizide or diazoxide, in order to stimulate or inhibit insulin release, respectively. Frozen sections of pancreata were incubated with ten ICA-positive IDDM sera and analyzed by indirect immunofluorescence. Two sera with a“beta-cell restricted”staining, five with an“all-islet cell”staining and three with a“mixed”pattern were employed. In all three groups, the highest end-point litres were obtained when pancreata of rats treated with glipizide were used. Intermediate litres were seen in control animals and the lowest litres were observed on pancreata from diazoxide-treated rats, regardless of the serum used. In contrast to these observations, no correlation between ICSA reactivily and islet cell activity could be demonstrated. Conflicting results concerning ICSA in previous reports and our failure to show a glucose regulation of ICSA reactivity, indicate that ICSA is a phenomenon with a low degree of specificity.The observation that the recognition of islet cells by autoantibodies is influenced by the melabolic state of the islelsin vivosuggests that the level of autoantigen expression could be of importance in determining the intensity of the autoimmune destructive process present at the onset of IDDM.

ISSN:0891-6934    

DOI:10.3109/08916939308993326

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The oral administration of CII by gavage to WA/KIR rats before a conventional arthritogenic challenge with bovine CII in FIA reduced the incidence (by 23%) and delayed the onset of collagen-induced arthritis in about 50% of the animals. Selective changes in B cell and T cell responses to CII in animals treated this way are interpreted to indicate a state of tolerance or hyporesponsiveness to CII. Tolerant animals made less serum antibody, to bovine and rat CII, of the IgG2b isotype and more of the IgG1 isotype.Phenotypic and functional analysis of peripheral lymph node cells showed that those from tolerized animals expressed less MHC Class II, proliferated less and secreted less IgG2b anti-CII antibody in response to stimulationin vitrowith CII when compared with cells from non-tolerant animals. However, this depression of the immune responses to CII seenin vitrowas overcome when the cells were incubated with increasing amounts of CII. Tolerance could be transferred to normal animals. Spleen cells, and nylon wool-filtered splenic T cells (but not mesenteric lymph node cells) adoptively transferred hyporesponsiveness to normal recipients which were then less susceptible to collagen-induced arthritis. Transfer of serum from gavaged animals did not modify the susceptibility of normal recipients to arthritis. Spleen cells from gavaged animals suppressed proliferative and antibody responses in co-culturesin vitrowith lymph node cells from animals immunized with CII in FIA. The suppressive spleen cell population contained more cells expressing MHC Class II, in both the CD8+and CD4+populations. These studies show that the oral administration of CII alters the subsequent immune response to the arthritogenic challenge and indicate that this oral tolerance of CII is due, not to clonal deletion or anergy, but rather to an antigen-driven active suppression mechanism that affects both T cells and B cells, most likely through the action of regulatory cytokines IL-4, IL-10 and TGFβ.

ISSN:0891-6934    

DOI:10.3109/08916939308993327

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The metabolic state of peritoneal macrophages is defined quantitatively for spontaneous ROI release and compared with those produced after cell contact with phorbol myristate acetate (PMA) or zymosan (OZ) particles. Peritoneal exudate cells (PEC) from EAP animals spontaneously released significantly more ROI than cells from controls rats, indicating that mononuclear phagocytes from autoimmune rats were more activated than populations cells arising from rats injected with BSA, with CFA or non-injected. These findings could indicate anin vivoactivation state in PEC from autoimmune rats different from that obtained with heterologous antigens or CFA immunization procedures. The release of ROI induced afterin vitrostimulus was, in general, higher in cells from autoimmune than in BSA or CFA treated rats.This differential responsiveness between the MAG, BSA and CFA injected macrophage populations could indicate that during the autoimmune process the autoantigen/s could amplify the inflammatory response triggered by them.Although release of oxygen metabolites represents only one of many potential mechanisms of tissue injury, this together with the lesions observed in the prostate gland indicate that oxygen radicals could be involved in this autoimmune disease.

ISSN:0891-6934    

DOI:10.3109/08916939308993328

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Pregnancy in ATP women is not unusual. The problem of this association concerns the possibility of disease transmission to the fetus due to the crossing of maternal antiplatelet antibodies through the placenta. Maternal risk factors predictive of neonatal thrombocytopenia, can be identified as follows: severe thrombocytopenia, previous splenectomy, high litre of PA-IgG and/or SPB-IgG. In 63 pregnancies in ATP patients, we have evaluated whether the above maternal risk factors, considered in the third trimester, can provide useful criteria for the prediction of neonatal thrombocytopenia. In the third trimester, the distribution of maternal risk factors was as follows: 0 in 7 cases, 1 in 27 cases, 2 in 15 cases, 3 in 12 cases, 4 in 2 cases. From a statistical evaluation, the neonatal platelet values and the maternal risk factors seem inversely correlated (r = 0.437; p = 0.0005). In particular, neonatal and maternal platelet count correlated positively (r = 0.249; p = 0.025); moreover, neonatal platelet count correlated negatively with Splenectomy (r = - 0.209; p = 0.05), PA-IgG (r = - 0.401; p<0.0005) and SPB-IgG (r = -0.338; p<0.005). We tried to apply a multiple regression model for all the above parameters which appears statistically significant (p = 0.001); the variability was about 30%. This regression model could be validated if applied to a larger number of cases, and it could represent an alternative to the invasive methods used for the diagnosis of neonatal thrombocytopenia.

ISSN:0891-6934    

DOI:10.3109/08916939308993329

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The mechanisms that govern autoantibody production are still under debate. In particular, auto-antibodies can appear as a consequence of a polyclonal activation of B cells or as a consequence of an antigen driven B cell expansion. The molecular analysis of the variable regions of auto-antibodies arising during different clinical situations can help to understand the origin of auto-antibodies. We recently described the main light chain variable regions of polyclonal rheumatoid factors occuring during rheumatoid arthritis and suggested that the mutation pattern of these regions could reflect an antigen driven process. Using the same approach, we now report the molecular analysis of the same light chain variable region containing a VKIII segment of rheumatoid factors originating from a polyclonal activation of B cells during an in vivo Epstein-Barr virus infection, infectious mononucleosis. The cDNA derived from rheumatoid factor synthetizing cells were amplified by two sets of polymerase chain reaction. The amplified products were cloned in M13mp 19 phages and sequenced. The nucleotide analysis of the VKIII containing VK regions shows that: 1) the rheumatoid factor activity is associated with the 3 VKIII genes (Kv 325, Kv 328 and Vg) already known to encode for monoclonal and polyclonal rheumatoid factors, 2) there is a preferential use of Kv 328 and Vg, each one of these genes being poorly mutated, 3) the CDR mutation rates of these genes is no higher than the framework mutation rates, 4) there is a restriction of the JK usage: Kv 328 derived gene segments rearrange exclusively with JK1, Vg preferentially rearranges with JK1 and JK4. These results mainly suggest that naturally occuring polyclonal activation of autoreactive B cells produces poorly mutated autoantibodies.

ISSN:0891-6934    

DOI:10.3109/08916939308993330

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939308993331

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939308993332

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor