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Biomedical subjects

N I Abdou

Publications and source records attributed to N I Abdou.

At least 19 recordsLinked to original sources
PubMed1992

Shift of private and not of cross-reactive anti-DNA idiotypes in systemic lupus erythematosus.

The shift of private idiotype (Id) and cross-reactive Id (CRI) on anti-DNA antibodies in a lupus patient KE was investigated during a 7-year period. Anti-private Id and anti-CRI activities were separated by affinity chromatography from rabbit (R)-anti-Ids raised against KE anti-DNA antibodies during active (1/84) and inactive (4/90) stages of the disease. Anti-CRI isolated from the 84 R-anti-Id appeared to recognize binding site-related Ids that are shared with KE non-anti-DNA antibodies, unrelated lupus patients' sera, and certain normal sera. Id expression on serial serum samples of KE using these fractionated R-anti-Ids as probes showed that the 1/84 private Id expression declined while the 4/90 private Id expression gradually increased. Expression of the CRI showed a relatively stable pattern. These results suggest that anti-DNA populations detected by anti-private Id can shift, while populations expressing CRI may stay stable.

Antibodies, Antinuclear↗
PubMed1992

Expression of inactive stage anti-dsDNA idiotypes on anti-ssDNA antibodies in a lupus patient during active stage of lupus cerebritis.

The possibility that idiotypes (Ids) defined on anti-double stranded DNA (dsDNA) antibodies during active and inactive stages of lupus (1/84 Id and 4/90 Id, respectively) were expressed on anti-DNA antibodies during a subsequent active period (9/90) of the disease was investigated in a lupus patient with lupus cerebritis. Using rabbit (R)-anti-Ids specific to 1/84 Id and 4/90 Id in inhibition assays, the 4/90 Id was shown to be expressed on the framework regions of anti-single stranded DNA (ssDNA) but poorly on co-existing anti-dsDNA antibodies of active (9/90) stage. The 1/84 Id was poorly expressed on both types of 9/90 anti-DNA antibodies. While the 9/90 anti-ssDNA significantly bound to immobilized ssDNA and several single-stranded polynucleotides, only ssDNA inhibited the binding of the anti-ssDNA to ssDNA, suggesting its monospecificity toward ssDNA. Western blot analysis following isoelectric focusing showed that a spectrotype pattern of 4/90 Id-positive 9/90 anti-ssDNA IgG was similar to that of the 4/90 anti-dsDNA, suggesting that they are of related clonal origin. The present study suggests the idiotypic heterogeneity of anti-DNA antibodies and the shift of antigen specificity within an idiotypically related anti-DNA population during exacerbation of the disease.

Animals↗
PubMed1992

Lupus-derived human monoclonal IgM anti-DNA antibody displays monospecificity, high affinity and private idiotype specificity.

A human monoclonal IgM k anti-DNA antibody, designated 2F7, was prepared by somatic hybridization of peripheral blood lymphocytes from a lupus patient with a human-mouse heterohybridoma cell line, K6H6/B5. 2F7 was tested for its antigen binding and idiotypic specificity by direct binding and inhibition enzyme-linked immunosorbent assays. 2F7 had a high binding activity to single-stranded DNA (ssDNA) but not to double-stranded DNA. It cross-reacted with single-stranded homopolymers with pyrimidine bases and double-stranded polynucleotides containing those homopolymers, suggesting that 2F7 recognizes a conformational determinant made up of both deoxyribose-phosphate backbone and specific nucleotide base. 2F7 did not cross-react with eight structurally unrelated self-antigens. Dissociation constant (Kd) of 2F7 for sonicated ssDNA was approximately 4.5 x 10(-9) M, indicating its relatively high affinity. Idiotypic characterization with rabbit anti-idiotype raised against 2F7 suggested that 2F7 expressed an idiotype at or near its antigen-binding sites that was not detected in sera from 20 unrelated lupus patients, 10 lupus family members and 10 normal individuals. These results suggest that certain IgM class anti-DNA antibodies in human systemic lupus erythematosus may arise by antigen stimulation and not simply by polyclonal B-cell activation.

Animals↗
PubMed1991

Detection and purification of antiidiotypic antibody against anti-DNA in intravenous immune globulin.

Pooled normal human IgG for therapeutic use, following depletion of anti-DNA, anti-Fc, and anti-F(ab')2 of normal IgG, expressed antiidiotypic activity against anti-DNA derived from lupus sera. The antiidiotype enriched by elution from anti-DNA affinity columns bound directly to anti-DNA IgG and inhibited the binding of lupus sera to DNA but did not bind to normal IgG or inhibit the binding of anti-tetanus toxoid to tetanus toxoid. Antiidiotypes in pooled normal sera may have a role in the clinical improvement seen in patients with autoimmune diseases receiving intravenous immune globulin.

Antibodies, Anti-Idiotypic↗
PubMed1991

Idiotypic and immunochemical differences of anti-DNA antibodies of a lupus patient during active and inactive disease.

IgG anti-DNA antibodies of a lupus patient during active and inactive stages of her disease were studied. There were no significant differences in the amounts, in double-stranded DNA-binding activity, or in complement-fixing ability between purified IgG anti-DNA antibodies of both stages. However, their idiotype (Id) expressions were different as revealed by binding to rabbit anti-Ids raised against each of the anti-DNA antibodies. Moreover, the active stage anti-DNA antibodies had higher activity and less cross-reactivity with polynucleotides. Dominant anti-DNA populations during the active and inactive stages of systemic lupus erythematosus are clonally and qualitatively different.

Antibodies, Antinuclear↗
PubMed1989

Antiidiotypic antibodies against anti-DNA antibodies in sera of families of lupus patients.

We searched for antiidiotypes directed against anti-DNA in sera of healthy family members of lupus patients. Controls were healthy individuals without a personal or family history of lupus. No significant differences were noted between the family members' and the control group's sera with respect to binding to DNA or to non-anti-DNA F(ab')2 fragments. Family members' sera had higher binding to anti-DNA F(ab')2 and to normal IgG F(ab')2 fragments (P less than 0.01). Sera of the family members had significantly higher binding to anti-DNA F(ab')2 than to normal IgG F(ab')2 fragments (P less than 0.0036). Inhibition experiments have shown that the antiidiotype is directed against the framework determinants and not against the antigen binding sites of the idiotype. The antiidiotypic antibodies were directed against cross-reactive anti-DNA idiotypes and were not restricted to the idiotypes of the lupus proband. Age, sex, and blood relationship to the lupus patient did not influence the presence of antiidiotypes in the family members. The possible role of environmental factors in the induction of antiidiotypes and the role of the latter in regulating anti-DNA antibodies are discussed.

Adult↗
PubMed1989

Immunoregulation of anti-islet cell antibody in insulin-dependent diabetes: failure to detect anti-idiotypic antibody following seroconversion.

A search was made for the presence of spontaneous auto-anti-idiotype in sera of three insulin-dependent diabetics when they converted from islet cell antibody positive to islet cell antibody negative states. Rabbit anti-idiotype specific for islet cell antibody was used as the positive control. Using an enzyme-linked immunoabsorbent assay, binding of the rabbit anti-idiotype to idiotype-coated plates could not be inhibited by islet cell antibody negative sera. Using this same assay, there was no significant difference in the binding of islet cell antibody positive or negative sera to either idiotype-coated or normal IgG-coated plates. Binding of islet cell antibody to pancreatic sections could not be inhibited by islet cell antibody negative sera in an immunofluorescent assay. Network regulation by auto-anti-idiotype does not seem to play a role in the decline or absence of islet cell antibody in the early phases of insulin-dependent diabetes mellitus.

Antibodies, Anti-Idiotypic↗
PubMed1989

Lack of correlation between HLA types and anti-idiotypic production in family members of a lupus patient.

Correlations of anti-single-stranded (ss) DNA, anti-F(ab')2, and anti-idiotypes to HLA types of 16 healthy family members of a lupus patient were studied. High levels of anti-ss DNA (63%) and anti-F(ab')2 (69%) were detected. Of the 12 family members who expressed HLA-DR2 antigen, 8 had anti-ss DNA and anti-F(ab')2 antibodies. One out of 3 family members who shared the same HLA phenotypes, A1B8DR2, of the proband had high levels of anti-idiotype directed against the proband's F(ab')2 anti-DNA. Though a high prevalence of A1B8DR2, of anti-ss DNA, and of anti-F(ab')2 in healthy family members of a lupus patient was found, anti-idiotypes against anti-DNA were not dependent on HLA-A, B, Dr.

Antibodies, Anti-Idiotypic↗
PubMed1989

Characterization of two anti-DNA antibodies bearing distinct idiotypes. Correlation with clinical manifestations.

Spontaneous idiotype shift of anti-DNA antibodies in systemic lupus erythematosus was shown to be associated with changes in the clinical manifestations of the disease. Characterization of two anti-DNA antibody preparations from the same lupus patient showed that lupus nephritis was associated with antibodies showing higher specific antigen-binding activity and avidity to DNA and presenting more cationic quality upon isoelectric focusing and Western blot analysis than the ones found in patients without renal involvement. Lupus cerebritis was associated with anti-DNA antibodies with different idiotypic characteristics not shared by anti-DNA antibodies present in lupus nephritis. Lupus cerebritis anti-DNA antibodies had less specific antigen-binding activity and avidity to DNA and did not show cationic quality. Idiotypic and immunochemical changes of anti-DNA antibodies in lupus may be associated with various clinical manifestations.

Antibody Affinity↗
PubMed1989

Effect of in vitro ultraviolet radiation on the binding capacity of anti-DNA and DNA in systemic lupus erythematosus.

The in vitro effects of various doses of ultra violet A (UVA) or UVB irradiation on DNA or anti-DNA as measured by their subsequent binding to anti-DNA or DNA were examined. Sera from 12 patients with active lupus were studied. UVA irradiation at 20-240 J/m2 or UVB irradiation at 2-24 J/m2 did not affect DNA or anti-DNA binding to anti-DNA or DNA, respectively. Modulation of the UV effect on DNA and anti-DNA by adding methylprednisolone, hydroxychloroquine and indomethacin at 10(-6) M did not alter the UV effect. UV light does not exert its effect directly on the binding of anti-DNA to DNA.

Antibodies, Antinuclear↗
PubMed1988

Spontaneous shift of anti-DNA antibody idiotypes in systemic lupus erythematosus.

Spontaneous shift in Id expression of polyclonal anti-DNA antibodies in a patient, BS, with SLE was investigated. BS had active lupus nephritis in 1982 and developed central nervous system lupus in 1986 without evidence of active nephritis. Two rabbit polyclonal anti-Id (BS-82 and BS-86 R-anti-Id) were raised against affinity-purified anti-DNA antibodies prepared from 1982 serum (BS-82) and 1986 serum (BS-86), respectively. In addition, murine monoclonal anti-Id was prepared against BS-82 Id. Direct binding assays showed that all three anti-Id had preferential binding to the immunizing anti-DNA antibodies (the homologous Id) and poor binding to anti-DNA antibodies prepared from the different dated sample of BS. This was confirmed by inhibition assays of binding of anti-Id to the homologous Id by various Id. Moreover, inhibition assays of binding of various Id to DNA by the R-anti-Id showed that the R-anti-Id was the most effective inhibitor for the homologous Id. Testing for Id expression in serial (1982 to 1986) serum samples of BS with the R-anti-Id as probes showed that BS-82 Id declined and was undetectable after October, 1984, whereas BS-86 Id was first detectable in July, 1985, and increased by June, 1986. These results clearly demonstrate spontaneous shifts in Id expression of human anti-DNA antibodies. The phenomenon of Id shift should be considered in any future strategy for the diagnosis and therapy of human autoimmune disease by anti-Id.

Antibodies, Antinuclear↗
PubMed1988

Private idiotypes on human polyclonal IgG anti-DNA antibodies are not expressed on coexisting IgM anti-DNA antibodies in systemic lupus erythematosus.

Sharing of private idiotypes (Id) on human polyclonal IgG anti-double-stranded DNA (dsDNA) with coexisting IgM anti-dsDNA was investigated using rabbit (R) anti-Id raised against IgG anti-dsDNA. The R-anti-Id showed specificity to private Id in or near the antigen-binding sites. The R-anti-Id poorly bound to the immobilized enriched IgM anti-dsDNA preparation but significantly bound to IgG anti-dsDNA preparation by a direct-binding ELISA (0.020 OD vs 0.295 OD, respectively). The R-anti-Id poorly inhibited the binding of IgM anti-dsDNA to immobilized dsDNA but significantly inhibited the binding of IgG anti-dsDNA to dsDNA (6% vs 55% inhibition, respectively). This was confirmed by poor inhibition of binding of the R-anti-Id to immobilized IgG anti-dsDNA by the enriched IgM anti-dsDNA preparation (maximum of 26% inhibition at 50 micrograms/ml). Nonsharing of private Id between IgG and coexisting IgM anti-dsDNA may represent the idiotypic diversity of human anti-DNA antibodies secondary to the frequent occurrence of somatic mutation on anti-DNA antibody during class switching.

Animals↗
PubMed1987

Effect of Fluosol DA 20% on antibody response to type 3 pneumococcal polysaccharide in rats.

Exchange transfusion with the oxygen-carrying resuscitation fluid, Fluosol DA 20% (FDA), interferes with the efficacy of penicillin therapy of pneumococcal infection in rats. Because this effect could not be attributed to an interaction between FDA and penicillin, the effect of FDA on the ability of rats to mount an antibody response to type 3 pneumococcal polysaccharide was tested. FDA (25 ml) was administered by isovolumetric exchange transfusion. Rats were immunized intravenously with 0.2 microgram of type 3 pneumococcal polysaccharide 3 days before, 1 day before, 1 day after, or 3 days after transfusion with FDA. IgM and IgG antibody responses were determined by ELISA 0, 3, 7, 10, 14, 21, and 28 days after immunization. When rats were immunized 3 days before or 1 day before transfusion with FDA, antibody levels were increased above control levels and remained relatively high through Day 28. When the animals were immunized 1 day after transfusion, antibody levels were approximately the same as in the control group. When the rats were immunized 3 days after transfusion, antibody levels were suppressed. These data suggest that FDA does not inhibit the humoral immune response when administered after or within 1 day before immunization, but does inhibit the response when immunization is given 3 days after transfusion.

Animals↗
PubMed1987

Polymyositis with hypokalemia: correction with potassium replacement in the absence of steroids.

A patient presented with typical polymyositis, but also with hypokalemia. Correction of potassium deficit without corticosteroids led to complete resolution of symptoms and laboratory abnormalities. Muscle biopsy performed after correction of the hypokalemia revealed focal fiber necrosis with regeneration and inflammatory infiltrate that contained, among others, many eosinophils. Hypokalemia should be considered in the differential diagnosis of polymyositis even in the face of an inflammatory muscle infiltrate.

Administration, Oral↗
PubMed1987

Anti-idiotypic antibody against anti-DNA in sera of laboratory personnel exposed to lupus sera or nucleic acids.

We tested for anti-DNA, anti-idiotypic, antinuclear, and lymphocytotoxic antibodies in the sera of three groups of normals: volunteers never exposed to lupus sera or nucleic acids (group I), research personnel handling nucleic acids (group II), and laboratory personnel handling lupus sera (group III). There was no significant differences among the groups with respect to levels of either single stranded or double stranded anti-DNA. Group I showed no significant differences in binding to F(ab')2 fragments of lupus anti-DNA, lupus non-anti-DNA or normal IgG. Compared to group I, groups II and III bound significantly higher to anti-DNA F(ab')2 fragments compared to non-anti-DNA F(ab')2 or normal F(ab')2 fragments. Sera from the three groups were negative for antibodies and all but one individual from group III had normal antinuclear antibody titres. These results indicate that sera of normals exposed to lupus sera or to nucleic acids contain an anti-idiotype directed against anti-DNA antibody. The possible role of these anti-idiotypes in regulating the anti-DNA antibody is discussed.

Antibodies, Anti-Idiotypic↗
PubMed1986

Study of anti-DNA antibodies prepared by DNA cellulose or Cibacron blue chromatography.

We prepared anti-DNA antibodies from sera of lupus patients by either DNA cellulose or by Cibacron blue chromatography. Eluates from both columns were studied with respect to recovery of IgG, recovery, purification and specificity of anti-DNA activity. An attempt was made to raise rabbit anti-idiotypic antibodies against both eluates. DNA cellulose chromatography--if DNA leakage was prevented--yielded 58% recovery and 58-fold purification of the anti-DNA activity present in the original purified IgG sample. 1% of loaded IgG was recovered. Cibacron blue chromatography yielded 32% recovery and 1.1-fold purification of the anti-DNA activity. 29% of loaded IgG was recovered. Eluates of Cibacron blue were not pure as shown by their high binding activity against an unrelated antigen, tetanus toxoid. Eluates from DNA cellulose were pure and did not show anti-tetanus toxoid activity. Rabbit anti-idiotypic antibodies could be raised only against eluates of DNA cellulose suggesting that the eluates of Cibacron blue did not contain enough idiotypes to induce anti-idiotypic antibodies. The characterization of the rabbit anti-idiotypic antibodies showed that it contained two populations, one against site-specific idiotypes and the other against framework idiotypes. Anti-DNA antibodies prepared by Cibacron blue had idiotypes similar to those prepared by DNA cellulose. The present study demonstrates that DNA cellulose chromatography--if leakage of DNA is prevented--can yield excellent recovery and purification of anti-DNA activity. Anti-DNA antibodies prepared by DNA cellulose were enriched and could induce anti-idiotypic antibodies in rabbits. Tube chromatography on Cibacron blue yielded poor recovery and minimal enrichment of anti-DNA activity.

Animals↗