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Biomedical subjects

M Zouali

Publications and source records attributed to M Zouali.

At least 73 records · Page 4Linked to original sources

Nucleic acid-binding specificity and idiotypic expression of canine anti-DNA antibodies.

Serum samples collected from eleven lupus dogs during an active phase of the disease all bound native and denatured DNA, poly(dT), poly(I) and poly(G). Nine bound poly(C); 10 bound poly(U); and 3 bound poly(A). Sera from 22 normal dogs were negative with all of these antigens. The canine sera were also probed for the presence of three idiotypic markers, one related to human lupus anti-DNA antibodies and two related to murine lupus antibodies. One canine lupus serum expressed idiotopes related to murine anti-DNA idiotype (Id) termed H130: (a) the canine serum bound to anti-H130 anti-Id; (b) it inhibited the binding of anti-H130 Id to its homologous Id; and (c) the anti-H130 Id inhibited the binding of the canine serum to DNA. These findings suggest that anti-DNA variable regions exhibit interspecies similarities, probably reflecting the conservation of the encoding gene segments through evolution.

Animals↗

Murine lupus anti-DNA antibodies cross-react with the hapten (4-hydroxy-5-iodo-3-nitrophenyl)acetyl, but immunization-induced anti-DNA antibodies do not.

The antigen-binding selectivity of 2 sets of anti-DNA antibodies from autoimmune mice and from normal mice was examined. Eighteen affinity-purified anti-DNA auto-antibodies from MRL-lpr/lpr mice were examined for binding to the haptens azobenzenearsonate, phosphorylcholine, (4-hydroxy-3-nitrophenyl)acetyl and (4-hydroxy-5-iodo-3-nitrophenyl)acetyl (NIP). Five of these autoantibodies bound to NIP-protein conjugates. In contrast, none of 12 monoclonal antibodies to single-stranded DNA or left-handed Z-DNA induced by immunization of BALB/c and C57BL/6 mice with nucleic acid antigens reacted with the tested haptens. In a reciprocal test of the relationship between anti-DNA and anti-NIP binding, we examined 24 monoclonal antibodies to NIP, from various strains of mice, for binding to DNA. One such antibody from a BALB/c mouse also bound to DNA. These results are discussed in the context of the mechanisms underlying autoantibody hyperproduction.

Animals↗

A rapid ELISA for measurement of antibodies to nucleic acid antigens using UV-treated polystyrene microplates.

Pretreatment of polystyrene microplate wells with certain doses of UV light enhances their capacity for binding to single-stranded DNA, double stranded DNA and various synthetic polynucleotides. The use of UV-irradiated plates to immobilize nucleic acid antigens provides a simple, rapid, and specific ELISA for measuring anti-nucleic acid antibodies. The assay is at least as sensitive as the more complex method of precoating plates with poly(L-lysine). It is useful for detection of anti-DNA antibodies in sera of systemic lupus erythematous patients, as well as in culture fluids of murine and human anti-DNA-secreting hybridomas.

Animals↗

Thymine and guanine base specificity of human myeloma proteins with anti-DNA activity.

To further our understanding of the molecular basis of DNA-autoantibody interactions, we have characterized the specificities of three IgG human myeloma proteins that bind DNA. We measured their binding to synthetic single- and double-stranded homopolynucleotides, random and alternating copolymers, oligonucleotides, and nucleotides or nucleosides conjugated to non-nucleic acid carriers. All three antibodies bound single-stranded nucleic acids, including both polyribonucleotides and polydeoxyribonucleotides. They varied in relative affinities for polynucleotides of varying base composition. Polymers containing the purines guanine or hypoxanthine and/or the pyrimidine thymine were most reactive with all three proteins. A myeloma protein that reacted with poly(G), poly(I), or poly(dT) also bound to the corresponding nucleosides or nucleotides conjugated to bovine serum albumin. None of the antibodies reacted with base-paired double-helical polynucleotides (double-stranded RNA, RNA-DNA hybrid or double-stranded DNA). The results indicate that base specificity is prominent in their reactions and that the accessible epitopes in single-stranded polynucleotides become masked upon base pairing in double-stranded helices. These findings suggest a model in which positions N1 and O6 of guanine and hypoxanthine and N3 and O4 of thymine interact with amino acids of the antibody-combining site.

Autoantibodies↗

IgG-subclass expression of anti-DNA and anti-ribonucleoprotein autoantibodies in human malaria.

To understand further the autoimmune phenomena associated with human malaria, we examined the IgG-subclass expression of antibodies to DNA and to ribonucleoproteins (RNP) in the serum of 99 patients with acute malaria. Of the sera, 22% were positive for single-stranded DNA (ssDNA), 18% for double stranded DNA (dsDNA) and 32% for RNP. Using a set of human IgG-subclass-specific murine monoclonal antibodies, we found that autoantibodies to dsDNA were predominantly expressed in the IgG1 subclass. In contrast, anti-ssDNA antibodies were more evenly distributed among the three other isotypes. Antibodies to RNP were essentially of the IgG1 and IgG2 isotypes. However, there was no correlation between these restricted IgG-subclass in the sera. These results are discussed in the context of previous findings of isotype expression of these autoantibodies in patients with the autoimmune disease systemic lupus erythematosus.

Acute Disease↗

Suppression of murine lupus autoantibodies to DNA by administration of muramyl dipeptide and syngeneic anti-DNA IgG.

We evaluated the effect of repeated subcutaneous administration of syngeneic anti-DNA IgG and muramyl dipeptide, a synthetic immunoadjuvant, to 6-mo-old (NZB X NZW)F1 female mice. This treatment had profound effects on both idiotype expression and anti-DNA antibody levels of morbid mice. It was also associated with appearance of anti-idiotypic antibodies specific for the injected antibody. These findings suggest that this approach with the use of synthetic immunomodulators and syngeneic antibodies may be of potential use in the management of autoimmune diseases.

Acetylmuramyl-Alanyl-Isoglutamine↗

Delta agent: a unique hepatotropic particle.

The delta agent is a unique virus-like human pathogen that superinfects individuals with hepatitis B virus. It is a defective "particle" that requires for its replication and expression obligatory helper functions provided by the hepatitis B virus. It is transmitted through blood products and body fluids via both parenteral and non parental routes. The recent description of an accessible animal model and a nucleic acid probe for delta agent should facilitate elucidation of the pathogenesis of delta-associated liver disease.

Acquired Immunodeficiency Syndrome↗

Evaluation of auto-antibodies in chronic mucocutaneous candidiasis without endocrinopathy.

Six patients with chronic mucocutaneous candidiasis (CMCC) were investigated for the presence of auto-antibodies during the course of the infection. Sera were tested for antibodies to native DNA (dsDNA) and denatured DNA (ssDNA), mitochondrial and microsomal antigens, smooth muscle, gastric parietal cells, basal membrane and skin intercellular substance, parathyroid glands, thyroglobulin and microsomal antigen, immunoglobulins and for anti-nuclear antibodies. Auto-antibodies were detected by radioimmunoassay, immunofluorescence, hemagglutination and other routine methods. Tests were performed at the end of the observation period, with the same batches of antigens and at the same time for all patients. Organ-specific antibodies (gastric parietal cells and intercellular substance) were found at low titers in five patients. Anti-smooth muscle antibodies were increased in two patients. In four patients antibodies to ssDNA were elevated. Moreover high titers of anti-ssDNA antibodies correlated well with disease activity after treatment with Ketoconazole in four tested patients. The possibility that C. albicans infection may induce auto-antibodies should be considered in assessing their disease activity significance in other chronic infected patients. The mechanisms of appearance of auto-antibodies and their immunopathological significance in CMCC are discussed.

Adolescent↗

Anti-DNA autoantibody activity and idiotypic relationships of human monoclonal proteins.

Previous studies showed that polyclonal anti-DNA antibodies from patients with systemic lupus erythematosus (SLE) share cross-reactive idiotypes (CRI). In this report, we used human myeloma proteins (HMP), isolated from the serum of patients with multiple myeloma or Waldenström macroglobulinemia, as probes to further explore this idiotypic cross-reactivity. Fourty-four HMP were tested for DNA-binding capacity and for expression of CRI associated with lupus anti-DNA antibodies. Anti-DNA IgG were immunoaffinity purified from the serum of patient TOF with severe SLE. A xenogeneic anti-idiotype antibody to this IgG was raised in rabbit. This anti-idiotype recognized CRI associated with the combining site of anti-DNA IgG from unrelated SLE patients. Using inhibition competitive-immunoassays, we found that these CRI were present on all but one of the DNA-binding HMP. Furthermore, we observed that these CRI were detectable on an IgG2 lambda, a HMP devoid of anti-DNA activity. These findings are in agreement with those previously obtained in similar studies using murine monoclonal anti-DNA antibodies. These converging results suggest that antibodies expressing anti-DNA-related CRI and antibodies exhibiting anti-DNA-binding affinity constitute overlapping molecular subpopulations.

Antibodies, Anti-Idiotypic↗

Antibodies to heterogeneous nuclear ribonucleoproteins in sera from patients with rheumatic autoimmune diseases.

Ribonucleoprotein (RNP) particles sedimenting at 40 S in sucrose gradients were prepared from calf thymus nuclei. They were identified as heterogeneous nuclear RNP (hnRNP) on the basis of size, electron microscopic examination, buoyant density, and protein electrophoretic patterns. Sera from patients with systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease were found to interact with hnRNP by counter-immunoelectrophoresis and enzyme-linked immunosorbent assay (ELISA). Small nuclear RNP (snRNP) were purified by immunoaffinity using a monoclonal anti-snRNP antibody immobilized on Sepharose beads. Inhibition of the ELISA assay for snRNP with anti-hnRNP Fab fragments and cross-over experiments revealed that the autoantibodies detected in human sera recognize common epitopes present on snRNP and hnRNP.

Antibodies, Antinuclear↗

Idiotype restriction in human autoantibodies to DNA in systemic lupus erythematosus.

Antibodies (Ab) to double stranded DNA (dsDNA) were immunoaffinity-purified from the serum of patient TOF with active systemic lupus erythematosus (SLE). Anti-idiotypic Ab to TOF anti-DNA were raised in rabbit. They were shown to recognize TOF F(ab')2 fragments, but they did not interact with human Ab of other specificities or with TOF IgG depleted of anti-DNA activity. In addition, their binding to TOF idiotype was specifically inhibited by DNA molecules. These anti-idiotype Ab therefore recognized idiotopes associated with a variable region of TOF anti-DNA-combining site. Thirty-one purified IgG anti-DNA preparations from unrelated SLE sera were able to inhibit this idiotype-anti-idiotype reaction by up to 90%. However, there was no linear correlation between anti-dsDNA Ab levels and idiotype-blocking capacity. These findings suggest that, in SLE, the idiotypic repertoire of autoAb to dsDNA is more restricted than thought previously.

Autoantibodies↗

Idiotypic interrelationship among human myeloma proteins with distinct antibody-binding specificities.

There have been several reports of human myeloma proteins exhibiting autoantibody activity. Such immunoglobulins represent therefore an appropriate system for investigating idiotypic diversity of human autoantibodies. Using this approach, we confirmed the marked idiotypic restriction of polyclonal anti-DNA autoantibodies and we showed that immunoglobulins without known binding affinity may express autoantibody-related idiotopes. These results are discussed in lights of recent concepts upon autoimmune processes and idiotypic interactions.

Antibody Specificity↗

IgG subclass distribution of autoantibodies to DNA and to nuclear ribonucleoproteins in autoimmune diseases.

Fifty-seven serum samples positive for antibodies to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA) or small nuclear ribonucleoproteins (snRNP) selected from patients with systemic lupus erythematosus and mixed connective tissue disease, were examined for the IgG subclass distribution of these autoantibodies. It was shown that antibodies to dsDNA were relatively restricted to IgG1 and IgG3 subclasses whilst antibodies to ssDNA were equally distributed throughout the four subclasses. Antibodies to snRNP were essentially restricted to the IgG2 isotype. These isotype distribution patterns contrasted with that observed for total serum IgG.

Antibodies, Antinuclear↗

A human monoclonal IgG1 with anti-idiotypic activity against anti-human thyroglobulin autoantibody.

Sixty-one human myeloma proteins (HMP) from patients with multiple myeloma and Waldenström macroglobulinemia were tested for anti-idiotypic (Id) activity against autoantibodies to double-stranded DNA, small nuclear ribonucleoproteins, and human thyroglobulin (HTg), by competitive radioimmunoassays and enzyme immunoassays. An IgG1, lambda HMP from patient BEN with anti-Id activity against antibodies to HTg is reported. IgG1 BEN was not directed toward human Fc fragments and its activity was not related to allotypic determinants. IgG1 BEN molecules recognized Id determinants (idiotopes) on F(ab')2 anti-HTg fragments, but not idiotopes of F(ab')2 fragments of antibodies of other specificities. This observation supports the general significance of Id network interactions in regulation and diversification of immune responses in man.

Antibodies, Anti-Idiotypic↗

Expression of anti-idiotypic clones against auto-anti-DNA antibodies in normal individuals.

A serum pool from 280 blood donors and individual samples from blood donors were assayed for anti-idiotypic activity to auto-anti-DNA antibodies by competitive radioimmunoassays. We found that serum from several normal blood donors inhibited the binding activity of anti-DNA antibodies affinity purified from the sera of patients with systemic lupus erythematosus. This inhibition was due to immunoglobulin molecules but was not due to rheumatoid factor activity. Antiallotypic antibodies were not responsible for the anti-anti-DNA activity detected. Because this inhibition was blocked by DNA molecules, the observed reactivity was probably caused by idiotype-anti-idiotype interactions. These results provide evidence that anti-idiotype antibodies against anti-DNA autoantibodies are present in certain normal human sera. Anti-anti-DNA antibodies could play a role in the regulation of autoimmunity to DNA.

Animals↗

[Demonstration of an abnormal increase of anti-T hemagglutinin titers in malaria infected patients].

An increased frequency of high titers of antibodies against A, B, ORh+ trypsinized, and ORh+ neuraminidase-treated human red blood cells was observed in the sera of Africans living in a malaria endemic area, and Europeans with primary malaria attacks. In the latter group, titers of agglutinins against neuraminidase treated RBC were increased in 84% of individuals and were of the IgM class. Inhibition experiments with beta-D-galactose and lactose showed that this agglutinin was directed to the T antigen of human RBC. Its possible implication in malaria related anemia is discussed.

ABO Blood-Group System↗