Role of HLA-B27 in Spondyloarthropathies

Khare, Sanjay D.; Luthra, Harvinder S.; David, Chella S.

doi:10.1007/978-3-642-85208-4_6

Cited by 6 publications

(5 citation statements)

References 65 publications

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“…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%

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

Oldstone

2014

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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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.

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Section: Molecular Mimicry and Autoimmune Diseasementioning

confidence: 99%

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

Oldstone

2014

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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“…A more meaningful model followed with our observations correlating several bacteria with HLA B27-associated ankylosing spondylitis (AS), an arthritic disease of humans. Epidemiological, bacteriologic, and immunologic evidence is firm for a strong relationship between AS, the hypervariable region of HLA B27, and several bacterial infections including those of Shigella flexneri, Yersinia enterocolitica, and Klebsiella pneumoniae (Brewerton et al 1973;Gilliland and Mannik 1986;Khare et al 1996;. Over 90% of patients who develop AS have the HLA B27 haplotype, but this haplotype occurs in only about 10% of the general population.…”

Section: Experimental Animal Models Of Molecular Mimicry and Autoimmumentioning

confidence: 99%

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

Oldstone

2005

Current Topics in Microbiology and Immunology

109

110

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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.

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“…One of the interesting and still controversial findings for an association of microbes with disease by the mechanism of molecular mimicry occurs with AS and bacterial infections (42)(43)(44)(45)(46). Epidemiologic, bacteriologic, and immunologic evidence is firm for a cor-relation between AS, the hypervariable region of HLA B27, and several bacterial infections including those of S. flexneri, Yersinia entercolytica, and K. pneumoniae.…”

Section: Correlation Of Molecular Mimicry With Human Diseasementioning

confidence: 99%

Molecular mimicry and immune‐mediated diseases

1998

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Molecular mimicry has been proposed as a pathogenetic mechanism for autoimmune disease, as well as a probe useful in uncovering its etiologic agents. The hypothesis is based in part on the abundant epidemiological, clinical, and experimental evidence of an association of infectious agents with autoimmune disease and observed cross-reactivity of immune reagents with host 'self' antigens and microbial determinants. For our purpose, molecular mimicry is defined as similar structures shared by molecules from dissimilar genes or by their protein products. Either the molecules' linear amino acid sequences or their conformational fits may be shared, even though their origins are as separate as, for example, a virus and a normal host self determinant. An immune response against the determinant shared by the host and virus can evoke a tissue-specific immune response that is presumably capable of eliciting cell and tissue destruction. The probable mechanism is generation of cytotoxic cross-reactive effector lymphocytes or antibodies that recognize specific determinants on target cells. The induction of cross-reactivity does not require a replicating agent, and immune-mediated injury can occur after the immunogen has been removed a hit-and-run event. Hence, the viral or microbial infection that initiates the autoimmune phenomenon may not be present by the time overt disease develops. By a complementary mechanism, the microbe can induce cellular injury and release self antigens, which generate immune responses that cross-react with additional but genetically distinct self antigens. In both scenarios, analysis of the T cells or antibodies specifically engaged in the autoimmune response and disease provides a fingerprint for uncovering the initiating infectious agent.

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Role of HLA-B27 in Spondyloarthropathies

Cited by 6 publications

References 65 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, Microbial Infection, and Autoimmune Disease: Evolution of the Concept

Molecular mimicry and immune‐mediated diseases

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