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T Muryoi

Publications and source records attributed to T Muryoi.

32 records · Page 2Linked to original sources
PubMed1990

Are the clonotypes of serum IgG anti-DNA antibodies associated with lupus nephritis in humans?

We analyzed isoelectrofocusing (IEF) patterns of anti-DNA antibodies originated from sera and the renal eluates of patients with systemic lupus erythematosus (SLE). The spectrotypic patterns of serum anti-DNA-antibodies were heterogenous and bands with single-stranded (ss) and double-stranded (ds) DNA were detected in the PI 5.5-6.5 and PI 8-9.5 regions when SLE sera were tested, whereas healthy subjects failed to form bands even at different saline concentrations. The renal eluates from normal subjects never bound to DNA whereas those from SLE glomeruli showed relatively restricted IEF patterns which were detected mainly in PI 6.0 and PI 8.5, showing that some anti-DNA antibodies may be nephritogenic. However, the spectrotypic patterns of serum anti-DNA antibodies in patients with active lupus nephritis were similar with those in patients lacking renal lesions. The reasons why IEF analysis failed to indentify specific clonotypes of nephritogenic anti-DNA antibodies are discussed in association with pathogenesis of lupus nephritis. This study also suggests that the use of a high concentration of 6M urea in an IEF analysis may be able to expose antigen-binding sites of the circulating immune complex (IC)-derived antibodies.

Autoantibodies↗
PubMed1990

Are the clonotypes of serum IgG anti-DNA antibodies associated with lupus nephritis in humans?

We analyzed isoelectrofocusing (IEF) patterns of anti-DNA antibodies originated from sera and the renal eluates of patients with systemic lupus erythematosus (SLE). The spectrotypic patterns of serum anti-DNA-antibodies were heterogenous and bands with single-stranded (ss) and double-stranded (ds) DNA were detected in the PI 5.5-6.5 and 8-9.5 regions when SLE sera were tested, whereas healthy subjects failed to form bands even at different saline concentrations. No differences were found for IEF patterns of anti-DNA antibodies between patients with lupus nephritis and those without. The eluates from SLE glomeruli showed relatively restricted IEF patterns which were detected mainly in PI 6.0 and 8.5; but those from normal subject did not. These data indicate that anti-DNA antibodies will be responsible for the pathogenesis of lupus nephritis. Specific clonotypes of serum anti-DNA antibodies, however, could not be defined in an association with renal lesions of SLE. This study also suggests that the use of a high concentration of 6 M urea in an IEF analysis may be able to expose antigen-binding sites of the circulating immune complex (IC)-derived antibodies, leading to detection of specific antibodies in vivo-formed IC.

Antibodies, Antinuclear↗
PubMed1989

In vitro manipulation of human anti-DNA antibody production by anti-idiotypic antibodies conjugated with neocarzinostatin.

Anti-DNA Id, 0-81, consist of 5 to 51% of Id in human anti-ssDNA antibodies; NE-1-Id shares 2 to 20% of those in anti-dsDNA antibodies. Thus, both 0-81-Id and NE-1-Id are of the cross-reactive Id that are commonly present among anti-DNA antibodies. In order to manipulate the production of anti-DNA antibodies by human PBL, we used mouse antiidiotypic mAb or those conjugated with a cytotoxic agent, neocarzinostatin. Treatment with the conjugates caused profound suppression of anti-ssDNA and anti-dsDNA antibody synthesis related to 0-81- and NE-1-Id. This was attributed to the specific killing of the clones bearing anti-DNA Id among the lymphocytes, evidenced by the indirect rosette formation tests. The Id-mediated suppression was not solely due to selective elimination of Id-positive B cells, because 50 to 92% of anti-DNA antibodies were suppressed by treatment with the conjugates. This was supported by flow cytometry analysis that showed a decrease of anti-Id-reactive cells when T cells were treated with the conjugates. This method, then, will permit an analysis of the question as to whether T cells reactive to anti-idiotypic antibodies might participate in the regulatory mechanism for anti-DNA production and, in addition, may lead to a new therapy for SLE.

Antibiotics, Antineoplastic↗
PubMed1989

Incidence of anti-DNA idiotype-positive cells in human peripheral blood.

Human anti-DNA idiotype (Id)-bearing cells in peripheral blood were sought using mouse monoclonal anti-Id antibodies to human monoclonal anti-DNA antibodies. Pretreatment with acid pH or pronase P or preincubation in human serum-free medium markedly decreased the number of anti-Id-reactive cells. Pronase P-treated cells were able to bind to anti-Id once more after incubation for 18 hr at 37 degrees C, indicating the resynthesis of internal idiotypic determinants on the cells. Antiidiotype-reactive cells retained the same idiotypes in their cytoplasma. The cells expressing anti-DNA idiotypes, termed 0-81 and NE-1, were detected in the circulation of most patients with active lupus nephritis but not in those of inactive systemic lupus erythematosus (SLE) and healthy subjects. The idiotype-positive cells occurred in up to 5-10% of B cells from some patients with SLE in the active stage but became undetectable in remission. A limited number of anti-DNA Id-positive cells responsible for anti-DNA production might be preferentially expanded during acute episodes of the disease in some patients with SLE.

Antibodies, Antinuclear↗
PubMed1989

Impaired accessory cell function of monocytes in systemic lupus erythematosus.

We studied the ability of monocytes from systemic lupus erythematosus (SLE) patients to act as accessory cells in an in vitro antibody response. Depletion of monocytes from peripheral blood mononuclear cells of normal subjects caused markedly diminished immunoglobulin (Ig) production but that of SLE did not. In order to evaluate the accessory cell activity of monocytes in in vitro immunoglobulin (Ig) production, we designed an accessory cell index of monocytes in the antibody responses. The studies revealed that Ig synthesis of isologous lymphocytes, mixed with monocytes from patients with active lupus nephritis, was significantly lower than those mixed with monocytes from healthy subjects. Moreover, the addition of graded numbers of monocytes of the former to unseparated peripheral blood mononuclear cells did not alter in vitro antibody production. These results indicate that monocytes from active SLE patients have an impared accessory cell function in an in vitro antibody response with no stimulating effect on suppressor cell activity.

Antibody-Producing Cells↗
PubMed1989

Protein-losing gastroenteropathy in association with immune deposits in gastrointestinal mucosal capillaries.

A 30-yr-old man presented with anasarca and visual disturbance. The serum albumin was 1.9 g/dl. Loss of albumin into the stomach and upper small intestine was demonstrated by technetium-99m (99mTc)-albumin scintigraphy. However, no anatomical lesions were found in the gastrointestinal tract. Renal function was normal, urinary protein was minimal, and hepatic function was near normal. A variety of autoantibodies, such as antinuclear antibodies, SS-A, SS-B, or Coombs' antibodies, were detected in serum in association with hypocomplementemia. Immunological studies revealed IgG, IgM, C1q, and C3 deposits in the walls of capillaries in the lamina propria of gastrointestinal mucosae. Combination therapy of prednisolone with an immunosuppressive agent improved the loss of albumin into the bowel and abnormal laboratory findings. This report indicates that the autoimmune process may contribute to the pathogenesis of certain types of protein-losing gastroenteropathy.

Adult↗
PubMed1988

Epstein-Barr virus-transformed B cells bearing idiotypes of anti-DNA autoantibodies.

Epstein-Barr virus (EBV)-transformed B cells obtained from healthy subjects had the same idiotypes of anti-DNA autoantibodies on their surface as those obtained from patients suffering from systemic lupus erythematosus. These clones secreted anti-single-stranded or anti-double-stranded DNA antibodies. Among them, some produced anti-DNA idiotype-positive antibodies but failed to bind DNA. This was confirmed by a competitive inhibition radioimmunoassay. It was then considered whether or not the expression of anti-DNA idiotype on B-cell clones related to the anti-DNA antibody activity in vivo. The amounts of anti-DNA antibodies were not associated with the incidence of idiotype-positive B cells in the EBV-transformed cell lines from normals. The results indicate that the clones committed to the synthesis of anti-DNA idiotype-positive antibodies commonly exist at a resting state in the circulation of healthy subjects, probably through the self-tolerance regulatory system.

Antibodies, Antinuclear↗
PubMed1988

Binding specificity of antiidiotypic autoantibodies to anti-DNA antibodies in humans.

Human antiidiotypic antibodies to anti-DNA antibodies can be separated into at least two categories based on their binding to anti-DNA, antiidiotypic antibodies, and antigens. One type was found mainly in inactive stage of SLE. The antiidiotypic antibodies appear to be directed towards idiotype (Id) determinants in the antigen-binding sites of anti-DNA antibodies. Antibody from patient T.K. acted like a mirror image of anti-single-stranded DNA antibodies, O-81, as determined by a competitive inhibition RIA. Antibodies from patient S.U. also seemed to be Ab 2 beta and Ab 2 gamma to anti-double-stranded(ds) DNA antibodies, NE-1. Most of normal subjects, on the other hand, had antibodies that bound to the human monoclonal anti-ds DNA antibodies, NE-1, NE-13, 7F4, and O-81. The Id-anti-Id interaction was not inhibited by the addition of DNA. Thus, normal subjects had Ab2 alpha activity that recognizes Id determinants in the framework region common among anti-DNA antibodies, whereas antiidiotypic antibodies in most SLE sera appear to show Ab 2 beta and Ab 2 gamma activity. The results provide evidence that the Id network system regulates immunological tolerance to DNA in humans.

Antibodies, Antinuclear↗
PubMed1988

Heterogeneity of anti-idiotypic antibodies to anti-DNA antibodies in humans.

Serum antibodies in some patients with systemic lupus erythematosus (SLE) were found to have specificity to idiotypes (Id) of 0-81 (human monoclonal anti-single-stranded DNA (ssDNA) antibody) but not to Id of NE-1 (human monoclonal anti-double-stranded DNA (dsDNA) antibody) or pooled human IgM. The interaction of the antibodies and 0-81 was blocked by the co-existence of free ssDNA. Some of SLE sera also showed preferential binding to Id determinants of NE-1, which included the antigen-binding sites of the dsDNA antibody. Some other SLE sera reacted with both Id of 0-81 and NE-13. Thus, there was heterogeneous population among human anti-Id autoantibodies to anti-DNA antibodies. The anti-Id activity was commonly detected in inactive SLE sera, and less frequently in normal controls, suggesting some regulatory role for anti-Id antibodies in the production of autoantibodies.

Animals↗
PubMed1987

Antigen inhibition of the interaction between murine monoclonal anti-idiotypic antibodies and human monoclonal anti-DNA antibodies.

Monoclonal anti-idiotypic (Id) antibodies to human monoclonal anti-DNA antibodies were obtained by a somatic cell hybridization. One, termed as D1E2, was directed to Id of anti-single-stranded (ss) DNA antibody (0-81) and the other, 1F5, to anti-double-stranded (ds) DNA antibody (NE-1). Each anti-Id antibody behaved like a mirror image of the corresponding antigens, when determined by competitive inhibition radioimmunoassay. Therefore, D1E2 and 1F5 are regarded as Ab2 beta or Ab2 gamma. These antibodies will make useful reagents to understand and manipulate the autoantibody production in human.

Animals↗
PubMed1986

Expression of idiotype on the surface of human B cells producing anti-DNA antibody.

We analyzed the idiotype (Id) expression on the surface of human anti-DNA antibody-producing cells. Murine monoclonal anti-Id antibodies with a specificity for determinants associated with the antigen-binding sites of human monoclonal anti-DNA autoantibodies were prepared. One anti-Id antibody reacted only with surface Id on anti-ssDNA-producing cells, but not with those on anti-dsDNA-producing B cell clones. Another anti-Id antibody did bind the surface Id on anti-dsDNA clones, but not those on anti-ssDNA clones. The interaction between anti-Id and surface Id was inhibited by pretreatment of the clones with DNA or appropriate polynucleotide antigens, or by preabsorption of anti-Id antibodies with free anti-DNA antibodies. Surface IgM and IgD expressed the same Id as the antibody secreted from the clones. The treatment of Id-positive clones by anti-Id antibody induced the redistribution of surface Id on the cells, indicating that these cells serve as targets for the regulatory action of anti-Id antibody.

Animals↗
PubMed1986

Selective elimination of anti-DNA antibody-producing cells by antiidiotypic antibody conjugated with neocarzinostatin.

A new strategy was shown for the manipulation of autoantibody production in humans. Antiidiotypic antibody to human anti-DNA autoantibody was conjugated with neocarzinostatin (NCS), a cytotoxic agent, by using N-succimidyl 3-(2-pyridyldithio) propionate as a coupling agent. Human B cell clones, which produce anti-DNA autoantibodies, were killed by in vitro treatment with antiidiotype (Id)-NCS conjugates, while clones expressing an Id with irrelevant specificity were unaffected. These results indicate that treatment with anti-Id-NCS conjugates can act as a potent and specific means of generating immunosuppression of autoantibody production. This approach will have a significant advantage in aborting clones that are not effectively suppressed for the autoantibodies by anti-Id antibodies alone, and will result in a potential therapeutic treatment for systemic lupus erythematosus.

Antibiotics, Antineoplastic↗
PubMed1985

Monoclonal human anti-DNA antibodies from EB virus-transformed lymphocytes of systemic lupus erythematosus (SLE) patients.

Sixteen monoclonal human anti-DNA antibodies were obtained from Epstein-Barr virus-transformed lymphoblastoid cells of patients with systemic lupus erythematosus (SLE) and were studied in terms of antigenic specificity. All of the antibodies showed polyspecificity to polynucleotides. Among them, some antibodies had a specificity to single-stranded (ss) DNA. Especially, O-8 antibodies showed a preference for polynucleotides with pyrimidine bases. The binding specificity of the antibody was also studied using different sizes of dT oligomers in order to assess the size of the epitope. It was revealed that oligonucleotides with a size of more than 25-30 nucleotides are required for inhibition of the antibody to ss-DNA. Other studies also demonstrated that anti-ss-DNA (O-8) antibody and anti-double-stranded (ds) DNA (NE-28) antibody bound to different combining sites in the same polynucleotides, poly(dT). These results suggest that some anti-ss-DNA antibodies are directed to the conformational structure related to the base sequence and that nucleic acids, therefore, might be responsible for the possible immunogenic stimulus causing the anti-DNA immune response. We also indicate that this type of antibody would be popular among serum anti-DNA antibodies in SLE.

Antibodies, Monoclonal↗