摘要:

In order to assess the frequency of autoimmunity markers in hepatitis C virus infection, 229 RIBA 2 HCV positive individuals were tested by ELISA and Immunoblot assay using as antigen rat liver microsomal and cytosolic proteins. Twenty-one out of 229 individuals (9%) showed anti-rat liver microsome antibodies by ELISA, but the titre was low (1:100 to 1:1,600). In Immunoblot, only 5 of these 21 ELISA positive sera recognized also rat liver microsomal proteins (MW between 30 to 64kDa). Antibodies against rat liver cytosolic proteins were found by ELISA in 14 out of 229 individuals (6%). Three of them showed a reactivity in Immunoblot to 42 kDa or 55 kDA proteins. In conclusion, HCV infection could induce an autoimmune response against rat liver microsomal and cytosolic proteins in a small number of subjects; the titre of antibodies being lower and the pattern of reactivity different in respect to patients with autoimmune hepatitis.

ISSN:0891-6934    

DOI:10.3109/08916939409014663

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Using the technique of in vitro enzymatic DNA amplification and dot blot hybridization with sequence-specific oligonucleotide (SSO) probes, a study of genetic polymorphism of HLA-DPB1 was performed in 83 unrelated patients with Graves' disease (GD), 48 patients with early onset myasthenia gravis (EOMG) and 100 normal British caucasoid subjects who were also tissue typed for HLA-A, B and DR antigens. HLA-DPB 1*0401 was the commonest allele in both patient and control groups with gene frequencies of 0.380, 0.333 and 0.445 for GD, EOMG and controls, respectively. No significant independent association was found with any HLA-DPB 1 allele. As expected, HLA-DR17 is significantly associated with Graves' disease (pc<8×10-3, RR = 2.9), while both HLA-B8 and DR17 are significantly associated with EOMG (pc<2×10-7, RR= 10.3 and pc<0.02, RR = 3.4, respectively)] HLA-DR2 is also significantly increased in EOMG patients who were negative for HLA-DR17 (pc<0.02, RR = 6.4). In addition, the co-occurrence of HLA-B8 with DPB 1*0402 was significantly commoner in patients with GD (p<0.021, RR = 6.2) and EOMG (p<0.0007, RR = 10.8) than in controls, although the HLA-DPB 1 *0402 by itself showed no significant increase.

ISSN:0891-6934    

DOI:10.3109/08916939409014664

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The cytokine interleukin 1β(IL-1) has been implicated as a pathogenetic factor in the initial events leading to insulin-dependent diabetes mellitus. Previous studies investigating the impact of IL-1 on diabetes incidence in spontaneously diabetic rodent models have been conflicting. IL-1 induces anorexia and previous studies are hampered by the lack of pair-fed controls to the IL-1 treated animals. We report that daily injections of 4.0μg/kg/day of recombinant human IL-1 (rhIL-1) for 13 weeks from 25-30 days of age did not alter the incidence of diabetes in the diabetes-prone (DP) BB rats (75%) when compared to pair-fed, vehicle treated controls (55%, p = 0.18), or to unhandled DP BB rats (80%, p = 0.71). However, IL-1 induced significantly higher blood glucose concentrations in the prediabetic period (p<0.00005) and at diabetes onset (p11 mmol/1 in the prediabetic period in 11/20 DP BB rats compared to 4/27 diabetes-resistant (DR) BB rats and 4/28 Wistar Furth (WF) rats (both p<0.004), compared to DP BB). Further, rhIL-1 induced fever in 11 weeks in the DP BB rats compared to 3 weeks in the DR BB and 6 weeks in the WF rats. Using high performance size exclusion chromatography specific anti-rhIL-1-antibodies were demonstrated in DR BB and WF, but not in DP BB rats. These antibodies neutralized the inhibitory effect of rhIL-1 on insulin secretion from isolated islets of Langerhans in vitro. The reduced pyrogenic and endocrine effect of rhIL-1 in the DR BB and WF rats compared to the DP BB rats could be explained by the impaired ability of the DP BB rats to produce anti-rhIL-1-antibodies. In conclusion, administration of rhIL-1 modulated the prediabetic period, and produced higher blood glucose concentrations at diagnosis, but did not change the diabetes incidence in DP BB rats. The results are not in conflict with the hypothesis that IL-1 is a pathogenetic factor in IDDM, caused by high local concentrations of rat IL-1 in the islets during early insulitis. The results also show the necessity of pair-feeding of the control group to the rhIL-1 group when interpreting data from experiments investigating rhIL-1 effects on diabetes development in animal models.

ISSN:0891-6934    

DOI:10.3109/08916939409014665

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Antiphospholipid antibodies (APL) are detected by both ELISA and tests for lupus anticoagulants (LA). We evaluated ELISA tests for IgG, IgM, and IgA isotopes of antibodies binding cardiolipin (CL) and phosphatidylserine (PS) in samples from LA patients presenting with recurrent miscarriages. All values were expressed in multiples of the normal median (MOM). In 32% (11/34) of cases, not only were all ELISA values at or below 2.5 MOM, but the distribution of these ELISA MOM values within the normal range was similar to distribution of values from LA negative controls with the same history. Neither the use of PS as the antigen nor the addition of IgA assays improved the correlation of ELISA results with the presence of LA. ELISAs are inadequate as the sole screening test for these separate, but often associated, families of APL.

ISSN:0891-6934    

DOI:10.3109/08916939409014666

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Type 1 (insulin-dependent) diabetes is strongly associated with the HLA genes encoding DR3 and DR4 and their associated DQ alleles. While 70% of all Caucasian diabetic patients carry the DR3-associated allele DQA1*0501, this allele also occurs in up to 40% of the healthy population. A DQA1 Bgl II 7.2 kb RFLP has been shown to identify a disease-associated subset of DR3-positive subjects. We examined the frequency of this RFLP pattern in 43 diabetic and 25 control DR3-positive subjects and found it to be present in 27 (65%) and 5 (20%) respectively (p = 0.0012). The promoter of the DR3-associated DQA1*0501 allele was amplified in four diabetic subjects who were positive, and four control subjects who were negative, for the 7.2 kb band. The promoter was digested with Bgl II to determine whether polymorphism within the promoter created a disease-associated Bgl II restriction site, which might influence disease susceptibility by an effect on gene transcription. No amplified promoter fragment contained a Bgl II restriction site, suggesting that the disease-associated 7.2 kb band does not result from DQA1 promoter region polymorphism but may be due to polymorphism elsewhere on the DR3 haplotype.

ISSN:0891-6934    

DOI:10.3109/08916939409014667

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Various autoantibodies to nuclear antigens were detected by ELISA in pooled sera of 15 ICR mice 9 weeks after infection with schistosoma. The binding of this serum with acute infection to cercarial extract was inhibited by prior incubation of the sera with DNA, polynucleotides and cercarial extract.Sera from 9 BALB/c mice with experimentaly induced lupus, reacted with cercarial extract. No binding was noted with normal mouse sera (NMS). Similarily, sera of SLE patients (N = 113) reacted with the parasite extracts in a higher incidence (14.2%) compared to NHS (3.7%) (P<0.05).Immunoblot analysis showed common features to SLE sera reacting with two antigenic“groups”. The first are antigens that also were recognized by sera of mice infected with schistosomiasis (60, 85, and 94 kDa cercarial proteins). The second group entailed proteins that bound with SLE sera only (10-18 kDa, 29 kDa and 52 kDa).It can be concluded that antinuclear autoantibodies can be found in sera of acute infected mice with schistosomiasis, while SLE sera may react with 3 schistosomal extracts in a higher incidence than NHS (P<0.05). These results suggest an autoimmune response in schistosomiasis. It is possible that a parasite infection (as bilharzia) may be one of the“trigger”mechanisms for SLE in a subject with the suitable immunogenetic and hormonal background.

ISSN:0891-6934    

DOI:10.3109/08916939409014668

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Multiple sclerosis [MS] is a chronic inflamatory disease of the central nervous system which has been postulated to be a T cell mediated disease. We examined proliferation of mononuclear cells to OKT3 mAb, Con A, ionomycin plus PMA and human myelin basic protein in subjects with relapsing-remitting and chronic progressive multiple sclerosis. Age and sex matched controls demonstrated a good proliferation to anti-CD3 mAb whereas subjects with relapsing-remitting multiple sclerosis showed a significantly decreased anti-CD3 mAb response. There was no difference in mitogen, ionomycin plus PMA or human MBP proliferation between controls and MS subjects. There was also a trend for decreasing anti-CD3 mAb proliferation in patients with chronic progressive multiple sclerosis compared to controls. LPS significantly decreased anti-CD3 mAb proliferation in controls but not in the MS subjects. An abnormality of signal transduction via the CD3 T-cell receptor complex in T cells and responsiveness to the immunomodulatory effect of IFN inducers may exist in multiple sclerosis.

ISSN:0891-6934    

DOI:10.3109/08916939409014669

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Experimental SLE can be induced in susceptible mice by their immunization with the human monoclonal anti-DNA antibody that bears a major idiotype-16/6 Id. The SLE afflicted mice produce a variety of autoantibodies including anti-DNA antibodies. It was of interest to find out the effect of DNA on the induction of the experimental disease. To this end, mice were immunized with combinations of 16/6 Id and DNA. The results indicated that whereas mice primed with 16/6 Id developed high titers of antibodies to the 16/6 Id and a variety of autoantibodies typical to the experimental SLE, preimmunization of mice with ssDNA led to a reduction in the 16/6 Id specific antibodies and in the autoantibody titers. No significant differences could be detected in the clinical manifestations which are present in the mice with experimental disease (increased erythrocyte sedimentation rate, leukopenia, proteinuria and glomerular immune complex deposition) in all mice immunized with 16/6 Id including those pretreated with DNA. Thus, no direct correlation exists between the autoantibody levels and the clinical pathology, and probably other factors are involved in the development of the experimental disease.

ISSN:0891-6934    

DOI:10.3109/08916939409014670

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Oligosaccharides can be of fundamental importance to glycoprotein function. Glycosylation abnormalities are present in rheumatoid arthritis (RA) and may be associated with disease pathogenesis. To determine whether similar disease mechanisms occur in the MRL-lpr/lpr autoimmune arthritic mouse, studies on B lymphocyte galactosyltransferase (GTase) have been carried out. In MRL mice, a significant reduction in peripheral blood lymphocyte (PBL) GTase activity was found when compared to their paired splenic (SP) GTase activity (- 69%, p = 0.002) and histocompatible non-autoimmune control CBA/Ca mice (- 67%; p = 0.002). The changes in PBL GTase activity are similar to those found in RA and on further analysis, using mixing experiments in the presence of purified human milk GTase, this reduction was shown not to be due to the presence of a soluble intracellular GTase inhibitor. Furthermore when examining MRL derived hybridoma cells producing IgG, significantly reduced GTase activity was detected in the rheumatoid factor (RF) producing hybridoma cells compared to those secreting an irrelevant antibody (- 21%, p<0.05). Together these findings suggest that the glycosylation changes observed in this study, and those reported previously in RA, are tissue-specific, may result from cells trafficking from centres of disease activity and are not the result of direct enzyme inhibition. It is now important to further understand the mechanisms controlling glycosylation and relate disease associated changes with those occurring as part of normal cellular physiology.

ISSN:0891-6934    

DOI:10.3109/08916939409014671

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939409014672

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor