Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T cells (CD8+) with specific suppressor activity against anti-dsDNA antibody (16/6 Id+) were generated in vitro. The cells were established from BALB/c-enriched T cells exposed in vitro to silica beads coated with the pathogenic anti-DNA idiotype, 16/6. The idiotype specificity of the suppressor cells was demonstrated by (a) specific induction of a decrease in proliferative response of T helper cell lines specific for the pathogenic idiotype (16/6 Id), when exposed to the idiotype, with no effect on T cell lines with other specificities, e.g., against human IgM or synthetic polypeptide. (b) Effectively suppressing in vitro antibody production of anti-16/6 antibody, employing 16/6-primed B cells and specific helper T cell line. The 16/6 Id-specific Ts cells were found to be MHC restricted. Weekly intravenous injections of 10(7) 16/6 Id-specific Ts cells given to BALB/c mice at different stages of experimental SLE disease prevented the clinical, serological, and pathological manifestations. This effect was characterized by decreased titers of autoantibodies (e.g., anti-DNA, anti-Sm antibodies) in the sera, by abolishment of the proteinuria, leukopenia, and the increased ESR, followed by decreased immunoglobulin deposition in the kidneys. Treating the mice with control IgM-specific T cells did not affect the above parameters. These studies demonstrate the ability to generate Ts cells specific for pathogenic idiotypes. The method might be employed therapeutically to modulate the course of autoimmune conditions.
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PMID:Modulation of SLE induction in naive mice by specific T cells with suppressor activity to pathogenic anti-DNA idiotype. 183 87

To study immune reactive and thrombotic mechanisms involved in chronic renal allograft rejection, Lewis rat kidneys were transplanted into bilaterally nephrectomized Brown Norway recipients tolerant of LEW erythrocyte antigens. Such BN rats fail to produce anti class I MHC alloantibodies after insertion of a LEW kidney. The LEW renal allografts experience a transient rejection episode without proteinuria followed by the development of chronic rejection, clinically characterized by glomerular proteinuria in the presence of stable renal function. Immunohistological studies of such chronically rejected LEW renal allografts showed the occurrence of glomerular and interstitial infiltration of predominantly monocytes and T cells. CD4-positive T cells dominated over CD8-positive T cells in the chronically rejected LEW renal grafts. IgG deposition was found deposited throughout the renal vasculature--this in contrast to IgM, which was observed only in the glomerular vasculature. Glomerular antibodies were not directed to endothelial class II MHC antigens, and showed only weak complement fixation as demonstrated by C3 staining. Selective glomerular IgM deposition was associated with vascular (platelet-containing) thrombi, and focal and segmental fibrinoid necrosis. In contrast, acutely rejected LEW renal grafts in unmodified BN recipients showed IgM deposition as well as thrombus formation throughout the entire renal vasculature. The results demonstrate that the antibody response to endothelial--and, in particular, glomerular endothelial non-MHC antigens--may bring about chronic vascular renal allograft rejection. How the formation of glomerular thrombotic lesions may be assisted by endothelial reactivity to cytokines from local immune reactive cells is discussed.
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PMID:Chronic renal allograft rejection. Selective involvement of the glomerular endothelium in humoral immune reactivity and intravascular coagulation. 187 89

HgCl2 induces an autoimmune syndrome in Brown Norway rats that involves synthesis of anti-glomerular basement membrane (GBM) antibodies and development of nephritis with high proteinuria. HgCl2-induced changes in the composition of leukocyte populations and in the expression of MHC antigens in lymphoid and nonlymphoid organs were investigated by flow cytometry and immunohistochemistry. An early increase of CD4+ splenocytes was followed by a transient proliferation of CD4+ as well as CD8+ and B lymphocytes in peripheral lymphoid organs; in contrast, progressive depletion of the thymic cortex was found. B lymphocyte activation involved mainly the IgG1 and IgE isotypes. Nonlymphoid organs were infiltrated by MHC class II antigen expressing CD4+ and CD8+ T lymphocytes and monocytes; secondary to infiltration, mainly epithelial cells, being the main target of infiltrating cells, showed increased expression of MHC antigens. In glomeruli a 2.7-fold increase of CD8+ lymphocytes occurred after HgCl2-administration. The diverse autoimmune phenomena observed in this study fit with the hypothesized involvement of T lymphocytes autoreactive with MHC class II antigens. Apart from anti-GBM autoantibodies, a role for autoreactive CD8+ T lymphocytes must be considered in the pathogenesis of the HgCl2-induced autoimmune syndrome.
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PMID:Mercuric chloride-induced autoimmunity in the brown Norway rat. Cellular kinetics and major histocompatibility complex antigen expression. 305 91

The influence of genetic factors on the susceptibility of the rat to cationic antigen-induced in situ immune complex glomerulonephritis was investigated. The levels of proteinuria developing in 11 inbred strains of rats differing in MHC and in genetic background varied markedly. Susceptibility was not MHC associated but resided in the genetic background.
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PMID:Genetic factors influence level of proteinuria in cationic antigen-induced immune complex glomerulonephritis in the rat. 315 28

Thymic maturation processes including MHC restriction and self-recognition require intimate association of thymocytes and stromal cells. Compared to the thymic architecture of various "normal" control strains of mice, defects in the thymic microenvironment have been demonstrated in New Zealand black (NZB) mice. Moreover, it is well known that NZB(H-dd) mice, when crossed with NZW(H-2u) mice, (NZB x NZW)F1, display a unique spectrum of autoimmune disease manifestations, including murine SLE. Using an extensive panel of monoclonal antibodies that define the thymic microenvironment, we examined two additional strains of (NZB x H-2u)F1 mice: (NZB x C57BL/10.PL)F1 and (NZB x PL/J)F1 mice to investigate the contributions of the H-2 and non-H-2 loci to the thymic abnormalities previously documented to occur in murine lupus. NZB, NZW, and (NZB x NZW)F1 mice were studied concurrently as were two additional control strains C57BL/6 and C57BL/10Sn. NZW mice had a normal thymic architecture as did the other H-2u mice and the control strains. In contrast, (NZB x NZW)F1 mice had a significantly altered thymic microenvironment; mild thymic abnormalities were also found in (NZB x PL/J)F1 but not in (NZB x C57BL/10.PL)F1. As expected, (NZB x NZW)F1 mice developed elevated titers of autoantibodies to DNA, proteinuria, and decreased life span. Interestingly, only (NZB x PL/J)F1 mice had increased levels of IgM antibodies to dsDNA, but did not manifest IgG anti-DNA or reduced survival. Defects in thymic stromal cells are associated directly to autoimmunity and their origin appears to be determined by non-H-2 loci.
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PMID:Thymic epithelial cell abnormalities in (NZB x H-2u)F1 mice. 755 52

MRL-lpr/lpr mice spontaneously develop a severe autoimmune syndrome, characterized by massive generalized lymphadenopathy, arthritis, arteritis, dermatitis and immune complex-mediated glomerulonephritis. Bone marrow transplantation (BMT) from MHC-matched systemic lupus erythematosus (SLE)-resistant donors to susceptible recipients has proved effective in correcting autoimmune manifestations in autoimmune-prone mice. We investigated the effect of syngeneic BMT from MRL/lpr (donor) to immunocompromised MRL/lpr (recipient), after purging the bone marrow inoculum with MoAbs against mature T cells (anti-Thy 1.2). All the untreated mice developed lymphadenopathy and by the age of 36 weeks five of the eight were dead; in contrast, all the mice which underwent syngeneic BMT following acute immunosuppression with total body irradiation (900 cGy) (TBI) remained disease-free. In an additional experiment, it was found that conditioning with cyclophosphamide (CY) before BMT was more effective than TBI in inhibiting delayed-onset autoimmune manifestations (mean survival 350 days in the CY group and 305 days in the TBI group, versus 197 days in untreated controls). Under both immunosuppressive regimens T cell-depleted bone marrow grafts produced far better results than did unmanipulated BMT. Following syngeneic BMT the incidence of proteinuria and the level of serum anti-DNA (dd) antibodies were significantly reduced, compared with that of the age-matched untreated controls. CY was more effective than TBI in reducing the anti-DNA titres. Likewise, T depletion of bone marrow inocula before BMT induced a more drastic drop in autoantibodies, following both CY and TBI conditioning protocols. After syngeneic BMT (either CY or TBI) no signs of lymphadenopathy were observed even at an advanced age. Upon histopathological examination, the BMT-treated mice displayed normal glomeruli with occasional minimal signs of glomerulonephritis. Syngeneic T cell-depleted BMT following acute cytoreduction of anti-self immune lymphocytes may represent a new therapeutic approach for drug-resistant autoimmune diseases.
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PMID:Immunomodulation of autoimmunity in MRL/lpr mice with syngeneic bone marrow transplantation (SBMT). 769 9

The CD4-CD8- T cells that accumulate in lpr/lpr mice have previously expressed CD8, on the basis of studies of CD8 alpha gene demethylation. The actual requirement for CD8 interaction with class I MHC molecules to promote the appearance of CD4-CD8- T cells in lpr/lpr mice has also been suggested. To examine this point in more detail, the lpr mutation was bred onto a beta 2-microglobulin-deficient background (beta 2-m-/-). C57BL/6 (B6) mice homozygous for both the lpr mutation of the fas gene and inactivation of the beta 2-m gene (beta 2-m-/- lpr/lpr) develop less alpha beta T cell lymphadenopathy than the parental B6 lpr/lpr strain. This is caused by the near absence of CD8+ T cells and a considerable reduction in CD4-CD8- T cells, revealing an important role for positive selection on class I MHC molecules during the ontogeny of lpr CD4-CD8- T cells. Although absolute numbers of peripheral T cells are decreased in beta 2-m-/- lpr/lpr mice, they manifest a B cell lymphadenopathy with age. beta 2-m-/- lpr/lpr mice display only subtle indications of autoimmune disease with age, compared with parental B6 (beta 2-m+/+)lpr/lpr mice. These include limited histopathologic stages of kidney disease and lack of proteinuria, despite the presence of serum anti-DNA Abs. Thus, absence of class I MHC-positive selection of CD8+ and CD4-CD8- TCR-alpha beta + cells limits the autoimmune diathesis observed in beta 2-m+/+ lpr/lpr mice.
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PMID:Decreased CD4-CD8- TCR-alpha beta + cells in lpr/lpr mice lacking beta 2-microglobulin. 786 83

A 27-year-old female was admitted to our hospital in order to examine proteinuria and microscopic hematuria. Light microscopic findings of her kidney showed proliferation of mesangial cells and numerous interstitial foam cells. Immunofluorescent and electron microscopic findings revealed IgA nephropathy. Immunoperoxidase studies using monoclonal antibodies disclosed that interstitial foam cells were positive for antibodies of the monocyte/macrophage lineage and also expressed adhesion molecules (CD11a, b, c, LFA-1) and MHC-class II antigens. Hereditary nephritis as Alport syndrome was negated by her familial history and electron microscopic study. We considered that it was a rare and interesting case with numerous interstitial foam cells, because the patient did not have hyperlipidemia as in nephrotic syndrome.
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PMID:[A case of IgA nephropathy with numerous interstitial foam cells--analysis of infiltrating mononuclear leucocytes in renal tissue]. 808 80

BALB/c mice infected with Trypanosoma brucei and treated seven days after inoculation with Diminazene aceturate develop polyclonal B-cell stimulation, including production of antibodies to known nephritogenic autoantigens and glomerular disease associated with severe albuminuria. To investigate if the susceptibility for glomerular disease in this model is linked to MHC or non-MHC genes, we studied this disease in six mouse strains that were partly congenic for their MHC and partly congenic for their non-MHC genes. The course of the infection was measured by parasitemia and related to (auto)antibody production, proteinuria and glomerular deposition of immunoglobulins. The mouse strains could be divided into two groups. The first group consisted of the C57BL/6 (H-2b), C57BL/10 (H-2b) and B10.D2 (H-2d) strains, which proved to be relatively resistant to infection with Trypanosoma brucei (that is, spontaneous survival > 25 days). In sera of these mice antibodies to a broad range of antigens could be found 14 days after inoculation; no proteinuria was observed. The second group consisted of the BALB/c (H-2d), BALB.B (H-2b) and DBA/2 (H-2d) strains, which were relatively susceptible to the infection. In these animals proteinuria occurred and a broad polyclonal B-cell stimulation was seen 42 days after inoculation. No correlation was found between the specificity of circulating antibodies and the occurrence of proteinuria or a glomerular fluorescence pattern. These results indicate that in this model non-MHC genes govern the outcome of the infection as well as the development of polyclonal B-cell stimulation and proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Susceptibility for infection-related glomerulopathy depends on non-MHC genes. 845 61

In rats, transient prophylactic anti-CD4 therapy with the nondepleting mAB RIB5/2 prevents acute rejection of MHC-mismatched allografted kidneys and induces long-lasting unresponsiveness. However, little is known about long-term benefits of this prophylactic anti-CD4 regimen. Here we report experimental results of permanently accepted rat renal allografts after prophylactic anti-CD4 treatment in regard to signs of chronic rejection. Kidneys from Wistar Furth donors were orthotopically grafted into bilateral nephrectomized BDIX recipients under the cover of anti-CD4 treatment (20 mg/kg b.w). Kidney function was serially monitored by measurement of serum creatinine and urine protein excretion. After 100 or 300 days respectively renal allografts were harvested, histologically and immunohistologically assessed and intragraft cytokine gene expression determined. Serum creatinine increased in few allografted rats. 30% of the 300-day-old grafts had an increased proteinuria and higher degrees of glomerular sclerosis. In these grafts cellular infiltration was more pronounced. However, no activated leukocytes (IL-2 receptor positive) were detected. Correspondingly, intragraft gene expression of CD3, IL-10 and IFN gamma was low. The results of our study indicate that a prophylactic anti-CD4 regimen diminishes chronic rejection to a level comparable to isografted or naive mass-reduced or ischemic kidneys. Thus, the signs of chronic rejection observed seem to be mainly caused by alloantigen-independent processes.
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PMID:Assessment of chronic rejection in permanent accepted renal allografts in anti-CD4 treated rats. 873 73


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