Klebsiella Pneumoniae and HLA B27-Associated Diseases of Reiter’s Syndrome and Ankylosing Spondylitis

Schwimmbeck, Peter L.; Oldstone, Michael B. A.

doi:10.1007/978-3-642-74594-2_4

Cited by 16 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With these observations on hand, my postdoctoral fellow Peter Schwimmbeck and I profiled by computer HLA-B27 hypervariable regions and bacteria associated with Reiter's syndrome. (4,5,29,30) We found the homologies shown in Figure 3B. In addition to the homology of six consecutive aa between HLA-B27.1 residues 72-77 and K. pneumoniae nitrogenase residues 188-193, these shared sequences are hydrophilic, suggesting locations of molecules exposed to the cell surface.…”

Section: Molecular Mimicry and Autoimmune Diseasementioning

confidence: 84%

“…Herpes simplex virus and corneal antigens may be associated with herpes stromal keratitis, and insulin-dependent diabetes with antigens from Coxsackie B, rotaviruses, hepatitis C virus, rhinoviruses, and others that cross-react with islet antigen glutamate decarboxylase 65, proinsulin carboxypeptidase H, and so on. (19)(20)(21)(22)(23)(24)(25)(26)(27)(28) Our laboratory then tested the molecular mimicry hypothesis in several experimental models in vivo, (4,5,8,(29)(30)(31)(32)(33)(34) two of which are illustrated and discussed here. First, we knew that T cell immune responses to MBP led to the autoimmune disease allergic encephalomyelitis (EAE) in several animal species.…”

Section: T Cell Clones and Molecular Mimicrymentioning

confidence: 99%

“…Moreover, Reiter's and AS are associated with the HLA-B27 haplotype and with infections due to Shigella flexneri, Yersinia enterocolitica, and Klebsiella pneumonia. (29,30,(35)(36)(37)(38) Over 90% of individuals who develop AS have the HLA-B27 haplotype, with HLA-B27 present in only approximately 10% of the normal population. Genetic studies indicate that monozygotic twins show a discordance for AS, (39) indicating a compelling role for environmental factor(s).…”

Section: Molecular Mimicry and Autoimmune Diseasementioning

confidence: 99%

“…3B), (5) which corresponded to the hypervariable region of HLA-B27 into transgenic mice that expressed human HLA-B27. (41) K. pneumoniae was selected on the basis of our prior immunochemical analysis (29,30) ; S. flexneri has a strong correlation with Reiter's syndrome and AS. In the 1940s, Finland reported an epidemic of S. flexneri infections involving about 150,000 humans, 344 of whom developed Reiter's syndrome.…”

Section: Molecular Mimicry and Autoimmune Diseasementioning

confidence: 99%

See 3 more Smart Citations

Molecular Mimicry: Its Evolution from Concept to Mechanism as a Cause of Autoimmune Diseases

Oldstone

2014

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

View full text Add to dashboard Cite

On a clonal level, certain antibodies and T cells can interact with dissimilar antigens found in microbes and in host cells. More than 5% of over 800 monoclonal antibodies derived from multiple RNA and DNA viruses, as well as from a large number of T cell clones, engage in such interactions. Several of these cross-reactions, which we termed molecular mimicry, are against unique host proteins involved in autoimmune responses and diseases. Thus, molecular mimicry initiated as a host response to a virus or a microbial infection, but alternatively cross-reacting with an appropriate host-antigen, can be a mechanism for instigating an autoimmune disease. Molecular mimicry provides an explanation for the genetic observation that identical twins rarely manifest the same autoimmune disease and the documented epidemiologic evidence that microbial and/or viral infections often precede autoimmune disorders.

show abstract

Section: Molecular Mimicry and Autoimmune Diseasementioning

confidence: 84%

Section: T Cell Clones and Molecular Mimicrymentioning

confidence: 99%

Section: Molecular Mimicry and Autoimmune Diseasementioning

confidence: 99%

Section: Molecular Mimicry and Autoimmune Diseasementioning

confidence: 99%

See 2 more Smart Citations

Molecular Mimicry: Its Evolution from Concept to Mechanism as a Cause of Autoimmune Diseases

Oldstone

2014

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

View full text Add to dashboard Cite

show abstract

“…In the first type, identical amino acid sequences present in different protein molecules are recognized by a monoclonal antibody or T-cell clone. Examples of this first type of molecular mimicry include (1) identical amino acid sequences shared between the human leukocyte antigen (HLA) B27 major histocompatibility complex (MHC) class I antigen and a nitrogenase of Klebsiella pneumoniae and (2) mimicry between Theiler's virus and myelin basic protein (Fujinami and Oldstone, 1985;Schwimmbeck and Oldstone, 1989). The mimicry between the HLA B27 class I molecule and the microbial nitrogenase is believed to play a role in ankylosing spondylitis, arthritis and Reiter syndrome which are sequelae of bacterial infections.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mimicry

Cunningham¹

2009

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Molecular mimicry is structural, functional or immunological similarities shared between macromolecules found on infectious pathogens and in host tissues. Molecular mimicry plays an important role in immune responses to infection and in autoimmune diseases. Infection may induce autoimmune responses which attack and destroy body tissues or organs. Normally, the body is tolerant to self‐antigens which are present in individual tissues. In autoimmune disease, tolerance is abrogated to self‐antigens, and tissues or organs are destroyed by the immune system. Molecular mimicry of a self‐antigen by an infectious pathogen, such as bacteria and viruses, may trigger autoimmune disease due to a crossreactive immune response against the infection. Crossreactive antigen–antibody and T cell–antigen reactions are used to identify the mimicking macromolecules on the pathogen and in tissues or organs. These parameters define the concept of molecular mimicry. Key Concepts: There are three types of mimicry. Immunological mimicry between dissimilar epitopes on chemically different molecules has changed the concept that an antibody molecule must recognize only a single antigenic epitope. Although molecular mimicry was once thought by immunologists to be a ‘phenomenon’ or ‘nonspecific immune reaction’, mimicry is now considered to be a part of the normal immune system and plays an important role in protection against pathogens. Microbial infections may activate the immune system and lead to a loss of immune tolerance which could allow expansion of high avidity crossreactive B‐ or T‐cell clones which through molecular mimicry may lead to autoimmune disease. Mimicry has been shown to lead to the induction of autoantibodies which alter signalling in cells.

show abstract

Molecular Mimicry, Microbial Infection, and Autoimmune Disease: Evolution of the Concept

Oldstone

2005

Current Topics in Microbiology and Immunology

Self Cite

109

110

View full text Add to dashboard Cite

Molecular mimicry is defined as similar structures shared by molecules from dissimilar genes or by their protein products. Either several linear amino acids or their conformational fit may be shared, even though their origins are separate. Hence, during a viral or microbe infection, if that organism shares cross-reactive epitopes for B or T cells with the host, then the response to the infecting agent will also attack the host, causing autoimmune disease. A variation on this theme is when a second, third, or repeated infection(s) shares cross-reactive B or T cell epitopes with the first (initiating) virus but not necessarily the host. In this instance, the secondary infectious agents increase the number of antiviral/antihost effector antibodies or T cells that potentiate or precipitate the autoimmune assault. The formation of this concept initially via study of monoclonal antibody or clone T cell cross-recognition in vitro through its evolution to in vivo animal models and to selected human diseases is explored in this mini-review.

show abstract

Klebsiella Pneumoniae and HLA B27-Associated Diseases of Reiter’s Syndrome and Ankylosing Spondylitis

Cited by 16 publications

References 32 publications

Molecular Mimicry: Its Evolution from Concept to Mechanism as a Cause of Autoimmune Diseases

Molecular Mimicry: Its Evolution from Concept to Mechanism as a Cause of Autoimmune Diseases

Molecular Mimicry

Molecular Mimicry, Microbial Infection, and Autoimmune Disease: Evolution of the Concept

Contact Info

Product

Resources

About