摘要:

13 patients with HIV-related immune thrornbocytopenia (HIV-ITP) and 10 patients with chronic idiopathic thrombocytopenic purpura (C-ITP) were treated with a single course ofα-2b-Interferon (IFN 3×106IU sub-cutaneously for 12 d). The patients had platelet counts lower than 40×109/L and thrombocytopenia persisting for over 1 year (range 1–22 years); 7 patients were refractory to previous conventional therapy, 5 were responsive, and 11 had not been previously treated. The response to IFN was complete in 8 patients (platelets>100×109/L). partial in 7 (platelets 50–110×109/L); 8 patients showed no response. The treatment with IFN was stopped after 4 d in one patient due to a fall in platelet count. The maximal platelet count (median peak 116±55 SD×109/L platelets) was obtained after 13.7±2.98d and the improvement in platelet count was maintained for 22.8±8.6 d. No difference in platelets response was observed between HIV-ITP and C-ITP. The response to IFN seems to be related to the one obtained with previous treatments. Indeed 80% of the patients who were responsive to previous steroids, high dose immunoglobulins or azidothymidine (HIV-ITP) showed a complete or partial response while only 43% of the refractory patients showed a partial response; the positive response rate in previously untreated patients was 73%.

ISSN:0891-6934    

DOI:10.3109/08916939309077363

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The effect of iodine excess on thyroid function and on the immunological sequence of events leading to lym-phocytic thyroiditis (LT) was studied in the NB subline of BB/W rats to determine the mechanisms by which the level of iodine intake influences the development of LT in this animal model. Iodine supplemented water (500μg/l, Group I or 500 mg/l. Group 2) or non-iodine supplemented tap water (Group 3) was given to breeding pairs and their offspring ad libitum. A Wistar rat group, also given tap water (Group 4) served as controls. To determine the immunological sequence of events, the phenotypic nature of the infiltrating thyroid lymphocytes was examined by specific immunoperoxidase staining in BB/W and Wistar rats at 6, 9. 12, and 15 weeks. Antigen-presenting cells and class II (Ia) antigen expression on thyrocytes were also examined.The first immunological event apparent in the iodine-treated BB/W rats was a sharp increase in the number of la positive dendritic cells at 9 weeks compared with control BB/W and Wistar rats. In the iodine excess groups dendritic cells were associated with scattered areas of lymphocytic infiltration. comprising predominantly T helper cells (W3/25). T suppressor cells (OX 8) and IL-2 receptor positive activated T-cells (OX 39) were both present in small numbers. B:cells (OX 12) were absent. In addition. thyrocytes did not exhibit la antigen expression. By contrast, lymphocytic infiltration was not found at 9 weeks in control BB/W rats. At 12 to 15 weeks, there was not only a marked increase in the number of lymphocytes, but lymphocytes now formed into large aggregates in iodine excess treated BB/W rats. Immunoperoxidase staining showed that although T-helper cells were still the predominant cell type within the lymphocytic aggregates. iodine treatment had resulted in a reduced number of T-helper cells when compared with control BB/W rats. In addition, IL-2 receptor positive activated T cells and B cells were present in the lymphocytic aggregates of the iodine treated rats. Lymphocytic infiltration at this stage was associated with thyroid follicular cell destruction in the high iodine supplemented groups. Class II (Ia) antigen expression on thyrocytes was a late immunological event and only seen on thyrocytes in direct contact with lymphocytic aggregates.In conclusion, a high iodine intake accelerates the development of lymphocytic thyroiditis in the BB/W rat. Iodine appears to mediate these effects on the immunological process, by initially stimulating antigen-presenling cells and later activated T lymphocytes. la expression on thyrocytes was a late immunological feature, suggesting that it is a consequence rather than an initiating event in this autoimmune process. It is still not clear from the present study whether the initiating effects of iodine on antigen-presenting cells is a direct effect on immune effector cells, or whether it represents a response secondary to a toxic effect of iodine on thyroid subcellular structures.

ISSN:0891-6934    

DOI:10.3109/08916939309077364

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Experimental autoimmune thyroiditis (EAT) is an autoimmune disorder of the thyroid gland induced in susceptible strains of mice by thyroglobulin (Tg). We recently showed that low Mr (<10 kDa) Tg tryptic fragments and a 40 amino-acid peptide (F40D) from Tg could induce EAT as well as native Tg. Because it has been reported that autoantibodies (A-Abs) express VH families preferentially located in the D-proximal VH gene segment, we investigated whether A-Abs specific for one pathogenic peptide from Tg were also skewed towards D proximal VH gene segment.In that respecr. we immunized CBA/J mice with EAT inducer antigens of decreasing sizes: Tg (660 Mr),<10 kDa Tg trypic fragments or F40D peptide (4.9 kDa Mr) from Tg. The VH gene segments utilized by immune spleen cells were determined by hybridization to total spleen cell RNA previously deposited onto nylon membranes and densitometric scans. This study was conducted on days 7 and 9 after determination of the maximum amounts of mRNA coding for immunoglobulins and on day 28 when A-Ab levels are the highest. Results were compared to VH gene segment expression both in normal and adjuvant-injected mice.We found that immunization of CBA/J mice with EAT inducer antigens stimulate B cells the restriction of which, in terms of VH family usage, depends on the size of the immunizing antigen: the larger the antigen, the higher the numbers of VH families used. Moreover, we found that B cell stimulation consecutive to immunization with the peptidic antigen inducing EAT occurs in VH 452 family. a VH encoded by D-proximal gene segment.

ISSN:0891-6934    

DOI:10.3109/08916939309077365

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Congenic B10.BR/SgSnJ H-2kTla2mice were infected with a diabetogenic strain of coxsackievirus CB4 to correlate abnormalities of sugar metabolism with virus replication in islets, 64.000-Mr(64K) islet autoantigen expression, 64K antibody development, and pancreas histopathology in early and late infection. Plaque assay was used to measure virus replication, whereas immunoprecipitation of the mouse islet extracts with 64K antibody-positive and -negative human sera measured autoantigen expression and antibody development. The infected mice exhibited blood glucose values below that of the noninfected control animals at 72 h postinfection, this subnormal blood glucose persisted at 6 wk postinfection and later. A baseline expression of the autoantigen was detected in the noninfected mice; however, the infected animals did not overexpress the protein at 72 h postinfection or develop 64K antibodies after infection. Limited virus replication was detected in the islets at 72 h postinfection but not later. Acinar necrosis, but not islet loss due to mononuclear cell infiltration, was evident in the infected mice. The congenic mice did not develop hyperglycemia and appear to be diabetes-resistant, their beta cells were largely preserved. This may be due to limited virus replication in their islets or their failure to overexpress the autoantigen and develop 64K antibodies following the infection. Diabetes-susceptible mice, on the contrary, support active virus replication in their islets. overexpress the autoantigen at 72 h postinfection, and develop 64K antibodies and hyperglycemia following such infection (Gerling et al., 1988, 1991).

ISSN:0891-6934    

DOI:10.3109/08916939309077366

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We studied the effects of interleukins (IL) on in vitro IgM and IgG anti-DNA antibody production by splenic B cells from autoimmune disease-prone NZB×NZW (NZB/W) FI mice. It was found that different interleukins regulate phenotypically distinct B cells producing separate isotype of anti-DNA antibodies. IL-2 slightly but significantly inhibited the production of IgM anti-DNA antibodies. IL-4 and IL-6 significantly enhanced the antibody production, but the effects were not so marked and inconsistent, particularly with respect to IL-6. By contrast. the effects of IL-5 were remarkable, particularly on splenic B cells from young mice. As for IgG anti-DNA antibodies. IL-6. but not other interleukins, markedly up-regulated the antibody production by splenic B cells from mice over 6 months of age, in a dose dependent fashion. Thus, the ability of B cells to produce IgC anti-DNA antibodies appears to be dependent on the surface expression of IL-6 receptor (IL-6R) at the ages when the mice begin to develop the disease. Studies of the surface phenotypes showed that while the IL-5-sensitive major IgM anti-DNA producers were CD5+Lp-3(CD43)-sIgM+. the IL-6-sensitive major IgG anti-DNA producers were CDS−p-3+sIgM−. However, significant amounts of IgG antibodies were also produced, in the presence of IL-6, by CDS+Lp−3+sIgM+, but not by CDS−Lp-3+sIgM+B cells from 6-month-old mice. We suggest that surface phenotypes of anti-DNA antibody producers change from CD5+Lg 35−-sIgM+IL-5R+. CD5+Lp−3+sIgM'IL-6R+and subsequently to CD5−-Lp-3−-sIgM-(sIgG+)IL-6R+in NZB/W FI mice with aging.

ISSN:0891-6934    

DOI:10.3109/08916939309077367

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We previously reported that circulating natural thymocytotoxic autoantibody (NTA) and IgG-anti-DNA antibodies were the major serological characteristics of a substrain of SAM, SAM-P/1. We present here a study of ageing in which we further measured and compared various kinds of circulating IgG antibodies including anti-collagen type II, rheumatoid factor (RF). and anti-2,4,-dinitrophenol (DNP), between SAM-P/l and control SAM-R/1 mice. The results showed that age-associated increases in anti-collagen type II antibodies in SAM-P/1 were distinctively higher than those in SAM-R/1 when the mice were over 4 months of age, and the increases were significantly correlated with increases in NTA, anti-DNA antibodies, RF activities and anti-DNP antibodies. Anti-collagen type II antibody activity was not significantly inhibited by preincubating the antibodies with DNA, IgG-Fc and DNP-BSA samples. These findings suggest that antibodies specifically directed against collagen type II can be produced in a background of polyclonal B cell activation, and that these antibodies in association with NTA and anti-DNA antibodies may play a pathogenic role in the development of accelerated senescence in SAM-P/1 mice.

ISSN:0891-6934    

DOI:10.3109/08916939309077368

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Mouse strains BIO, B10.RIII, RIIIS/J and the Fl and backcross progeny arising from them were tested for susceptibility to porcine type II collagen-induced arthritis (PII-CIA). The clinically severe arthritis of rapid onset that is characteristic of PII-immunized B10.RIII mice developed predominantly in hybrid offspring that had inherited at least one copy of wild type T cell receptor (TCR) genes (Vβbgenotype) from the B10 or B10.RIII parent. The results indicate that, in the development of PII-CIA, mice expressing the H-2r/rhaplotype preferentially utilize TCR Vp genes that are normally encoded within the TCR Vβgenomic deletion region of RIIIS mice (Vβc). After aggressive immunization with PII, the use of alternative TCR Vβgenes, encoded outside of the RIIIS deletion region, produced a high IgG antibody response that was cross-reactive with mouse type II collagen (MII) and equivalent to that of B10.RIII mice, but only a very mild, late onset arthritis of 56% (27/48) incidence in RIIIS male mice and 28% (10/35) incidence in RIIIS female mice. In comparison, B10.RIII mice routinely developed early onset of PII-CIA of significantly higher incidence (100%; p<0.005) and four-fold greater severity, even after milder immunization protocols. The data are compatible with the proposal that the clinically weak CIA response of RIIIs mice may be primarily antibody driven while the severe CIA of B10.RIII mice reflects the added inflammatory effects of collagen-reactive effector-T cells in the joint. The apparent concordance of TCR Vβutilization in the murine T cell response to MAM (a superantigen produced by M. arthritidis), to MIS-Ia(a retroviral superantigen). and to homologous type II collagen is discussed.

ISSN:0891-6934    

DOI:10.3109/08916939309077369

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Experimental autoimmune myocarditis could be produced in mice by repeated injection of syngeneic heart extract together with Klebsiella pneumoniae O3 lipopolysaccharide (KO3 LPS) as a powerful adjuvant. Histological changes in the cardiac lesions were characterized by infiltration with mononuclear cells in the myocardium, degeneration and loss of myocardial fibers, and replacement of granulation tissues. No such cardiac lesions were produced in mice receiving injections of heart extract alone or KO3 LPS alone. Development of the autoantibody and the delayed type-hypersensitivity (DTH) against syngeneic heart extract was found in mice immunized repeatedly with the mixture of heart extract and KO3 LPS. Moreover, definite cardiac lesions were produced in normal recipient mice by transfer of sensitized spleen cells from hyperimmunized mice. Therefore, it was suggested that those cardiac lesions were caused by the autoimmune mechanism. Our methodology provided a new experimental murine model for autoimmune myocarditis.

ISSN:0891-6934    

DOI:10.3109/08916939309077370

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Autoimmune thyroid disease (AITD) is often familial and serological HLA disease associations have been described in many different populations. However, such HLA disease associations are weak and the precise molecular contribution of HLA antigens to thyroid disease susceptibility remains unknown. Much of the data available are cross-sectional and few studies have explored familial inheritance of AITD at the molecular level. We have, therefore, examined the inheritance of AITD in multiplex and multi-generational families using restriction fragment length polymorphism (RFLP) analysis of DNA digested with the restriction enzyme BamHl and probed with a full length human HLA-DQ beta cDNA probe. Thirty seven subjects in 7 informative families were available for study. Eleven subjects had Graves' disease and 4 were diagnosed as having Hashimoto's thyroiditis. Segregation of polymorphic fragments enabled genotyping of each individual to produce fully informative families. LOD scores were computed, using the LIPED program, for dominant and recessive models of inheritance, for recombination fractions of 0.01 to 0.5 for each sex, and for penetrances of 0.1 to 1.0. The results showed that maximum LOD scores were negative for all of the inheritance models tested. If the primary locus for AITD were in the HLA region, LOD scores would be highly positive. These data. therefore, provide strong evidence against a disease locus for AITD in linkage disequilibrium with the HLA-DQ beta locus.

ISSN:0891-6934    

DOI:10.3109/08916939309077371

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Vascular heparan sulfate proteoglycan (vHSPG) has an important role in the normal vasculature, including hemostasis, lipolysis and other vascular functions. These functions are mediated by both the glycosarninogly-can and protein core moieties of vHSPG. Autoimmunity to vHSPG has been demonstrated to play a role in vascular injury in animal models, and is present in patients with autoimmune vascular disease. However, most previous studies of human autoimmunity to vHSPG have only investigated heparan sulfate glycosaminoglycan epitopes. In the current investigations. autoantibodies to the protein core of vHSPG in sera from patients with systemic lupus erythematosus (SLE) were investigated. vHSPG protein core was prepared by chemical deglycosylation. Competitive immunoinhibition ELISA and immunoblotting imrnuno-assays were established employing monoclonal antibodies to vHSPG protein core. SLE sera were demonstrated to contain IgG autoantibodies reactive with the vHSPG protein core by immunoblotting. Human autoantibodies to vHSPG protein core were not inhibited by heparan sulfate confirming their protein core reactivity. Competitive immunoinhibition studies employing a solid phase radioimmunoassay also confirmed the reactivity of human sera with vHSPG protein core. By ELISA, a significant increase in the occurrence of anti-vHSPG protein core antibodies was noted in SLE sera. While most previous investigations have demonstrated autoimmunity to heparan sulfate, the presence of IgG autoantibodies to vHSPG protein core demonstrates that the entire vHSPG proteoglycan is the target of autoimmunity in SLE.

ISSN:0891-6934    

DOI:10.3109/08916939309077372

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor