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M Zouali

Publications and source records attributed to M Zouali.

82 records · Page 5Linked to original sources
PubMed1982

High titres of anti-T antibodies and other haemagglutinins in human malaria.

The prevalence of antibodies against (i) human red blood cells (RBC) of A and B groups, (ii) trypsinized O Rh+ RBC and (iii) neuraminidase treated O Rh+ RBC were investigated both in sera of Africans from a malaria endemic area of Upper Volta and in sera of Europeans with acute malaria from a Paris hospital. An increased frequency of high titres of haemagglutinins was observed against A and B as well as O Rh+ trypsinized human RBC, thus confirming previously published results. In addition, agglutination of neuraminidase treated RBC showed that the titres were increased in about 40% of Africans studied and in about 80% of patients with acute malaria. Using agglutination with a specific anti-T lectin and inhibition with two ligands, it was found that sera of malarious patients contain high titres of antibodies directed against the T antigen of neuraminidase treated RBC. The mechanisms of appearance of high titres of autohaemagglutinins in malaria and their possible interference in the anaemia associated with this disease are discussed.

ABO Blood-Group System↗
PubMedDate not supplied

Nonrandom features of the human immunoglobulin variable region gene repertoire expressed in response to HIV-1.

Characterization of the immune response toward HIV is important for understanding the basic mechanisms of the disease and may give essential information for development of an anti-HIV vaccine. Paradoxically, although HIV infection is associated with a strong antibody response to structural and nonstructural HIV proteins, this immune response does not seem to halt disease progression. Both quantitative and qualitative B-cell abnormalities are associated with disease progression. The immunological abnormalities in HIV-1 infection include abnormal cytokine production and expansion of HIV-1-specific B-cell precursors that may reach 40%. There is also evidence that gp120 exerts a B-cell superantigen-like activity on human B-cells through binding to gene products of the third heavy-chain variable region family (VH3). This property of gp120 may induce abnormal mechanisms of selection of the antibody repertoire. It may also account for the apparent paucity of anti-gp120 antibodies expressing VH3 genes and for the polyclonal activation seen in the early stages of HIV infection. This expansion would reflect specific stimulation of VH3 B-cells, but not all B-cells. It would then be followed by a significant deletion of this B-cell subset. Finally, autoimmune phenomena have been described in HIV infection, and several hypotheses have been put forward to account for such associations. On the basis of the superantigen concept discussed above, one may suggest that gp120 may trigger B-cell subsets bearing receptors with specificities for self-components. This would explain the multiplicity of autoantibody specificities seen in this disease.

B-Lymphocytes↗
PubMedDate not supplied

Human autoantibodies and their genes.

We undertook an analysis of the B cell repertoire at both the germline and somatic levels. To assess the content and organization of the IgH-V and IgK-V loci in SLE, endonuclease-generated polymorphisms were used to characterize individual variations within the human V gene segments. The results are compatible with the conclusion that this disease is not caused by major abnormalities in the structure, size, or organization of the IgV loci. We propose that hyperproduction and lupus-associated autoantibodies arises through a two-stage mechanism whereby a general activation of the multireactive preimmune B-cell repertoire precedes oligoclonal expansion of selected B cell clonotypes.

Autoantibodies↗
PubMedDate not supplied

Molecular characterization of human monoclonal antibodies specific for several HIV proteins: analysis of the VH3 family expression.

We have analyzed the heavy-chain variable (VH) region genes expressed by a panel of human monoclonal antibodies derived from an immunized volunteer, an AIDS patient and seropositive asymptomatic donors, and specific for HIV-1 env, pol and gag gene products. The third complementarity-determining regions show a high complexity with unconventional gene recombination events. Most of the VH genes utilized are also frequently encountered in other immune responses. Their sequences are, in general, typical of an antigen-driven immune response. Molecular mechanisms that generate high-affinity antibodies are then effective during HIV infection. Remarkably, VH3 family, which dominates the human antibody repertoire, is barely encountered among anti-HIV antibodies.

Antibodies, Monoclonal↗
PubMedDate not supplied

Tracking immunoglobulin variable-gene expression in HIV infection.

B-cell superantigens (SAgs) interact with normal human nonimmune immunoglobulins (Igs) independently of the light-chain isotype, and activate a large proportion of the B-cell repertoire. Recently, the major envelope protein of human immunodeficiency virus 1 (HIV-1), gp120, was found to exhibit SAg-like properties for B cells with potential pathological consequences for the infected host, including accelerated apoptosis and progressive loss of B cells. This unconventional mode of interaction contrasts with its binding to immunization-induced antibodies, which requires the tertiary structure of the heavy- and light-chain variable regions. Examining the temporal development of V(H)3+ antibodies in HIV-1-infected subjects over a 7-yr period showed that V(H)3+ antibodies specific for the gp120 SAg-binding site are deficient. Quantification of V(H)3+ antibodies, which impart protective responses to infectious agents, in serum samples from HIV-seropositive slow progressors and from patients who progressed to AIDS-related manifestations reveals that paucity in V(H)3+ antibodies is a marker of rapid clinical decline. Remarkably, anti-gp160 V(H)3+ antibodies show a gradual decrease in progressors and vary with time, depending on the viral load. Thus, V(H)3+ antibodies could play an important role in protection, and their underexpression may accelerate disease progression. Investigation of the structural basis of the interaction between human Igs and gp120 shows that the viral gp120 SAg can interact only with a subset of human V(H)3+ Igs. A number of amino acid-positions present primarily in the first and third framework regions of the Ig heavy-chain variable regions correlate with gp120 binding. These residues partially overlap with the Staphylococcus aureus protein A-binding site for V(H)3+ Igs. Overall, these interactions could represent a novel mechanism of humoral deficiency resulting from the capacity of a viral SAg to impact an important subset of the B-cell repertoire and to induce B-cell death by apoptosis.

B-Lymphocytes↗
PubMedDate not supplied

[Heterohemagglutinins in human malaria: immunopathologic implications].

The prevalence of heterohemagglutinins was investigated both in sera of Africans from a malaria endemic area of Upper Volta and in sera of individuals with acute malaria from a parisian hospital. Hemagglutinins against horse, sheep, goat, chicken, pigeon and duck red blood cells were tested. The results showing an increased frequency of high titres of these hemagglutinins are discussed in terms of the mechanisms leading to autoantibody hyperproduction in malaria.

Animals↗
PubMedDate not supplied

Idiotypic/antiidiotypic interactions in systemic lupus erythematosus: demonstration of oscillating levels of anti-DNA autoantibodies and reciprocal antiidiotypic activity in a single patient.

This work was designed to investigate the occurrence and evolution of autoantiidiotypic antibodies to double-stranded DNA in systemic lupus erythematosus (SLE). Serum samples from a patient with SLE who was submitted to repeated therapeutic plasmapheresis for 57 weeks were examined for the presence of autoantiidiotypic antibodies to DNA. Anti-DNA antibodies were affinity-purified from a serum sample obtained at the beginning of the observation period. Anti-anti-DNA activity, directed toward structures within the binding site of anti-DNA autoantibodies but not antibodies of another specificity, was detected in the serum of the patient. In addition, the decrease in the levels of anti-DNA antibodies took place concomitantly with a reciprocal increase in the autologous anti-idiotype. These results indicate that anti-DNA and anti-anti-DNA antibodies coexist in the serum of this patient, and suggest that antiidiotypic interactions may play a role in the modulation of idiotypic expression in SLE.

Animals↗
PubMedDate not supplied

Trigger mechanisms of autoantibody production.

The random combinatorial assembly of Ig variable (V) gene elements leads to the generation of a proportion of antibodies with high affinity to self. Under normal conditions, the corresponding B-cells will be clonally deleted, rendered silent, or switched to a different specificity. In systemic autoimmunity, however, anti-self high affinity antibodies are overexpressed. We have been trying to uncover the molecular choreography that underlies the production of aggressive autoantibodies in SLE. Here, we studied B-cell clones producing anti-DNA autoantibodies that bear the human pathogenic 0-81 idiotypic marker, an idiotype present in 72% of immune complexes, and in 100% of renal eluates from patients with active SLE. In contrast to other lupus idiotypes, this marker is present in the circulation of most patients with active lupus nephritis, but not in inactive SLE or healthy subjects. Molecular cloning, nucleotide sequencing, and comparative genomic PCR revealed that lupus antibody variable genes incurred extensive somatic selection events. There is also evidence that the corresponding B-cells underwent essential primary light-chain variable rearrangements. We conclude that, in SLE, B-cells are the target of antigenic selection. We also propose that a subset of B-cells may be unable to revise their receptor and extinguish their high affinity for self.

Amino Acid Sequence↗
PubMedDate not supplied

Antibody epitopes probed by immunoselected phage-display library peptides in members of a family with various rheumatic manifestations.

OBJECTIVE: The random peptide combinatorial phage library approach overcomes the problem of lack of structural information about the aetiological agent or the antigen responsible for a given disease. Here, we used such a strategy to gain insight into the aetiology of rheumatoid arthritis (RA). METHODS: We analyzed the reactivity of serum antibodies from a family with various rheumatic manifestations against RA-immunoselected nanopeptides displayed on phage particles. RESULTS AND CONCLUSION: We found that within the same family, there was a difference in antibody reactivity against the peptides tested. The IgG isotype of the peptide reactive antibodies indicated that the observed reactivities were not related to the presence of polyreactive IgM antibodies. Furthermore, it is unlikely that the observed reactivity was due to rheumatoid factors (RF), since two patients who were positive for the immunoselected Pep3 peptide (LSSREPQAR) were RF negative. We also found that the serum of one patient with polyarthralgias also reacted with the same peptide bound by the RA serum, which may suggest the implication of a common aetiological agent in the apparition of this antibody reactivity. Finally, we noted that one patient with Sjögren's syndrome had antibodies to the RA peptide, which may indicate a potential relationship between these two autoimmune diseases.

Arthritis, Rheumatoid↗