Peptides as DNA mimics: cross-reactivity and mimicry in systemic autoimmune diseases

Fournel, Sylvie; Muller, Sylviane

doi:10.1007/s00018-002-8507-6

Cited by 4 publications

(2 citation statements)

References 53 publications

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“…In fact, a number of reports support this hypothesis (Zhao et al, 1998;Fournel and Muller, 2002). It has been suggested that infection can probably cause T cell activation in multiple sclerosis (MS) susceptible individuals (Hafler, 1999) and several microbial agents including C. pneumoniae have been implicated as the intracellular pathogens causing MS (Hunter and Hafler, 2000).…”

Section: Discussionmentioning

confidence: 99%

Is there a Relation between Chlamydia Infection and Primary Biliary Cirrhosis?

Leung

Park

Matsumura

et al. 2003

Journal of Immunology Research

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Over the past two decades, a number of studies have failed to provide direct evidence of specific microbial chronic infection in primary biliary cirrhosis (PBC). However, a recent report suggests that there is a specific association of Chlamydia pneumoniae in patients with PBC and that C. pneumoniae or similar antigens might play a role in the pathogenesis of disease. To determine if Chlamydia infection is associated with PBC, we applied a combination of immunological and molecular approaches to investigate (a) the serological reactivity against two common Chlamydia human pathogens, C. pneumoniae and C. trachomatis, by immunoblotting, (b) the presence of Chlamydia in liver samples of patients with PBC and controls by PCR amplification of Chlamydia specific 16S rRNA and (c) the presence of Chlamydia proteins in liver samples of patients with PBC and controls by immunohistochemical staining. By immunoblotting, C. trachomatis and C. pneumoniae specific serological antibodies were found in 52/57 (91.2%) AMA positive PBC, 7/33 (21/2%) of AMA negative PBC, 1/25 (4%) PSC, 0/15 (0%) Sjorgen's syndrome and 0/20 (0%) systemic lupus erythematosus patients and 0/20 (0%) healthy volunteers at 1:200 sera dilution. PBC sera reacted to Chlamydia and E. coli lysates in western blots up to a maximum of 10-4 dilution. However, PCR amplification of the Chlamydia specific 16S rRNA gene was negative in 25/25 PBC livers but positive in 1/4 PSC liver, 3/6 in other liver disease controls and 1/4 normal liver samples. While two commercially available specific monoclonal antibodies stained positive controls (Chlamydia infected HEp-2 cells) they failed to detect Chlamydia antigens in PBC livers. The detection of Chlamydia specific antibodies but not Chlamydia rRNA gene and Chlamydia antigens in PBC suggests that Chlamydia infection is not involved in PBC.

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Section: Discussionmentioning

confidence: 99%

Is there a Relation between Chlamydia Infection and Primary Biliary Cirrhosis?

Leung

Park

Matsumura

et al. 2003

Journal of Immunology Research

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“…However, the immunogenicity of these proteins for anti‐DNA response has not been determined. As an alternative approach, theoretical polypeptides recognized by anti‐DNA Abs have been searched using phage display [12]. Immunization of animals with these peptides was able to elicit anti‐DNA Abs [13–15], but no protein that contains these peptide sequences has been found.…”

Section: Discussionmentioning

confidence: 99%

A Single‐Stranded DNA‐Cross‐Reactive Immunogenic Epitope of Human Homocysteine‐Inducible Endoplasmic Reticulum Protein

et al. 2011

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The mechanism involved in generating anti‐DNA antibodies (Abs) remains unclear, as DNA is poorly immunogenic. Molecular mimicry between DNA and non‐DNA substances has been implicated as a possible mechanism. We previously reported that homocysteine‐inducible endoplasmic reticulum protein (Herp), which is induced by endoplasmic reticulum stress, is recognized by anti‐double‐stranded DNA (dsDNA) IgG from patients with systemic lupus erythematosus and that immunization with Herp elicits anti‐dsDNA Abs in BALB/c mice. In this study, we observed that anti‐single‐stranded DNA (ssDNA) Abs were also generated in Herp‐immunized BALB/c mice and established an anti‐Herp monoclonal antibody (mAb), HT4, which specifically cross‐reacted with ssDNA. The epitope of the HT4 mAb on Herp, ‘EPAGSNR’, was identified by screening a synthetic peptide library. The binding of the HT4 mAb to the peptide was competitively inhibited by ssDNA. Immunization of the epitope peptide elicited anti‐ssDNA Abs in BALB/c mice. These results indicate that the epitope exists in a human self‐protein, mimics ssDNA and shows antigenicity for anti‐ssDNA Abs in normal mice. Anti‐ssDNA Abs are often found in patients with drug‐induced lupus erythematosus. Treatment with representative drugs that cause drug‐induced lupus (chlorpromazine, procainamide and hydralazine) induced Herp expression and apoptosis in HeLa cells. These findings suggest that molecular mimicry between Herp and ssDNA is involved in anti‐ssDNA Ab production in drug‐induced lupus.

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