A common anti‐dna idiotype in sera of patients with active pulmonary tuberculosis

Sela, O; El-Roeiy, Albert; Isenberg, David; Kennedy, R C; Colaco, Camilo; Pinkhas, J; Shoenfeld, Yehuda

doi:10.1002/art.1780300107

Cited by 65 publications

(22 citation statements)

References 26 publications

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“…The answer may be that characieristic •pathogenic" idiotypes of autoantibodies may reside not only on autoantibodies but even on anti-bacterial or anti-viral atitibodies [48.50-53]. Indeed, previously we were able to demonstrate the presence of the 16/6 anti-DNA idiotype in 60% of sera of patients with active pulmonary tuberculosis [51]. Similar results were obtained in patients with Gram-negative bacterial infections, mainly klebsieila [52].…”

Section: Discussionsupporting

confidence: 53%

Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration

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Tomer

Stein

et al. 1995

Clinical and Experimental Immunology

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SUMMARYWegener's granulomatosis (WG) is a granuiomatous necrotizing vasculitis associated wiih the presence of ANCA, predominantly directed against proteinase 3 (PR3). The titres of ANCA correlate with disease activity and titre increases may precede disease exacerbations. Previously,, we have shown that it is possible to induce autoimmune disease (systemic lupus erythematosus (SLF) and anti-phospholipid syndrome) in naive mice following active immunization with human autoantibodies, namely anti-DNA and anti-cardiolipin. respectively. Tbe mice developed first anti-autoantibodies and, alter about 4 months anti-anti-autoantibodies (AbO. simulating autoantibodies (Ab,) in their binding activities, and their presence was associated with the development of disease manifestations, characteristic of tbe human disease. So far, there is no good animal model for WG. In the current study we have immunized mice with human ANCA with the aim of inducing experimental WG. In two separate studies 30 mice were immunized in their footpads with autoantigen-purilied IgG fraction (ANCA) from the sera of two patients with untreated WG. emulsified in Freund's complete adjuvant, followed 3 weeks later by ANCA injection in PBS. In tbe first experiment mice immunized with ANCA developed sterile microabscesses in the lungs after 8 months, and died after 8-15 months. In the second experiment, mice immunized with ANCA developed after 4 months mouse ANCA, with specificity botb to PR3 and to myeloperoxidase, as well as anti-endothelial autoantibodies (AECA), as sbown by radioimmunoprecipitation, Pathologically, the immunized mice developed proteinuria hut not haematuria, and histological sections of the lungs demonstrated mononuclear perivascular infiltration, while diffuse granular deposition of immunoglobulins was noted in the kidneys. Our results point to a pathogenic role of ANCA in WG, and confirm the importance of the idiotypic network in the etiopathogenesis of autoimmune conditions.

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Section: Discussionsupporting

confidence: 53%

Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration

Blank

Tomer

Stein

et al. 1995

Clinical and Experimental Immunology

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“…It is clear that the EVl-l 5 antibody and the Wa idiotypic family of RFs are more distantly related. Another parallel may exist in the production of a specific idiotypic family of anti-DNA antibodies after pulmonary tuberculosis or Klebsiella pneumoniae infections (65)(66)(67). Nonetheless, the striking serologic and structural similarity of these distinct antibodies may provide a crucial link between an antiviral response and an autoimmune disease.…”

Section: Discussionmentioning

confidence: 99%

Complete protein sequences of the variable regions of the cloned heavy and light chains of a human anti-cytomegalovirus antibody reveal a striking similarity to human monoclonal rheumatoid factors of the Wa idiotypic family.

Newkirk

Gram²,

Heinrich³

et al. 1988

J. Clin. Invest.

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The complete amino acid and nucleotide sequences of the variable regions of the heavy and light polypeptide chains of a human neutralizing IgGI anti-cytomegalovirus (CMV) antibody reveal a striking homology to IgM rheumatoid factors (RFs) of the Wa idiotypic family. The anti-CMV antibody and Wa RFs have in common VKIIIb, JKI, and VHIa gene segments but use different DH and JH gene segments. The anti-CMV antibody does not have RF activity and does not express the Wa idiotype. The Wa RFs do not have anti-CMV activity. A subset of Wa RFs, however, and the anti-CMV antibody do share several idiotypes on the VHIa and VKIIIb polypeptides. Since there are major differences in the antigen binding characteristics and some of the other expressed idiotypes, these data suggest that the D and J region amino acids are crucial to such specificities. Although the use of such highly homologous gene segments in different immune responses is well-documented in murine systems, these data represent the first such example in the human.

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“…Indeed, anti-DNA has now been linked to infec tion with bacteria [11][12][13], mycobacteria [14], viruses [15,16], as well as parasites in mice, rabbits, and man [17][18][19], Whether any of these infections contribute directly to SLE has not yet been determined, although a causal role of in fection in SLE would suggest that lupus is mechanistically similar to other autoimmune dieseases where foreign anti gens are clearly provocative. Further studies on the struc tural properties of anti-DNA antibodies arising in lupus and infection are in progress and should clarify these etiological relationships.…”

Section: Discussionmentioning

confidence: 99%

Immunochemical Properties of Anti-DNA Antibodies in the Sera of Patients with <i>Escherichia col</i><i>i</i> Bacteremia

Robertson

Pisetsky²

1992

Int Arch Allergy Immunol

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To assess the role of infection in anti-DNA antibody production, the DNA-binding activity of sera from patients with Escherichia coli bacteremia was analyzed. Among 8 patients with bacteremia documented by blood culture, 5 demonstrated increased levels of antibodies to single-stranded DNA from E. coli as measured by enzyme-linked immunosorbent assay. Sera from these patients also reacted with single-stranded DNA from other bacterial and mammalian species as well as certain synthetic polynucleotides including poly-dT and poly-dC. The isotype distribution of these antibodies and their avidity as assessed by competition enzyme-linked immunosorbent assay resembled, moreover, responses of patients with systemic lupus erythematosus. These results suggest that, during the course of infection with E. coli, some patients may produce antibodies with immunochemical properties similar to those arising in systemic lupus erythematosus.

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A common anti‐dna idiotype in sera of patients with active pulmonary tuberculosis

Cited by 65 publications

References 26 publications

Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration

Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration

Complete protein sequences of the variable regions of the cloned heavy and light chains of a human anti-cytomegalovirus antibody reveal a striking similarity to human monoclonal rheumatoid factors of the Wa idiotypic family.

Immunochemical Properties of Anti-DNA Antibodies in the Sera of Patients with <i>Escherichia col</i><i>i</i> Bacteremia

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