Elsevier

Medical Hypotheses

Volume 62, Issue 4, April 2004, Pages 493-498
Medical Hypotheses

Bacteriophages in autoimmune disease and other inflammatory conditions

https://doi.org/10.1016/j.mehy.2003.12.016Get rights and content

Abstract

There are several autoimmune diseases and other inflammatory conditions where an infectious aetiology is suggested by the epidemiology, clinical course and pathological findings. Many candidate bacteria and viruses have been considered as potential aetiological agents but mostly without firm proof. Bacteriophages are viruses that infect bacteria and may be found wherever bacteria are located, but would not be detected unless specifically sought. They have not previously been considered to be pathogens. Bacteriophages are immunogenic and therefore could play a role in the pathogenesis of autoimmune and other inflammatory diseases by acting as antigens on epithelial surfaces, bound to antibody as immune complexes, through molecular mimicry or possibly as superantigens.

Section snippets

The role of microbes in the aetiology of autoimmune disease and other inflammatory conditions

There are several autoimmune diseases and other inflammatory conditions where an infectious aetiology is suggested by the epidemiology, clinical course and pathological findings. It is now generally accepted that commensal bacteria play a role in the pathogenesis of inflammatory bowel disease [1], [2], [3]. Experimental data have shown that HLA-B27 transgenic rats spontaneously develop colitis and arthritis, however when they are bred in a germ-free environment, no or attenuated inflammation

Structure and genetics of bacteriophages

Bacteriophages, often referred to simply as phages, are viruses that infect bacteria. They are relatively simple structures and consist of nucleic acid contained within a protein coat. As in conventional viruses, the nucleic acid may be either DNA or RNA but not both. The protein coat or capsid is constructed from a large number of subunits or capsomeres. These capsomeres may be made up of single subunits or groups of subunits and are organised either helically to form a hollow tube as seen in

Hypothesis

My hypothesis is that bacteriophages may play a role as antigens in the pathogenesis of autoimmune disease and inflammatory conditions. Candidate diseases that could be explained by the hypothesis are inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis and other connective tissue disorders such as SLE, as well as multiple sclerosis, atherosclerosis and Kawasaki disease.

Lytic phages may be acquired when new bacteria carrying phages are introduced into the normal flora. Lytic

Published data supporting the hypothesis

A recent study has demonstrated that patients with abdominal aortic aneurysm are more likely to have been infected with strains of Chlamydia pneumoniae that harbour phages rather than strains without phages [28]. The phage-containing strains were identified by the detection in the patients’ sera of antibodies against phage capsid. The authors speculated whether the phage containing strains of C. pneumoniae are more virulent presumably by phage conversion, but no genes for a putative virulence

Testing the hypothesis

The hypothesis is testable but there may be difficulties. Panels of phage antigen could be screened against sera from patients with candidate inflammatory or autoimmune conditions, or screened for induction of T-cell proliferation or for their ability to act as superantigens. The difficulty would be choosing which of the potentially hundreds of phages might be likely candidates. If molecular mimicry is the mechanism, the number of likely phages could be narrowed down by comparison of host and

Conclusion

The hypothesis accounts for why bacteria have been implicated in the aetiology of some autoimmune and inflammatory conditions and why no proof of a pathogenic role for these bacteria has been proven. The hypothesis describes how bacteria may act as vectors for the actual aetiological agents, bacteriophages. The bacteriophages may cause disease as new antigens arriving with new bacteria, or be revealed as new antigens following induction in lysogenic organisms within the normal bacterial flora.

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