Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA-B27 is highly linked with a group of human diseases called spondyloarthropathies (SpA). Many of these disorders begin after an infection with an enterobacteria. The symptoms seen in patients with spondyloarthropathies are inflammatory pain in the spine and asymmetrical arthritis of lower limbs. Additional symptoms related to SpA include inflammation in the eyes, bowel, and skin. The autoantigen(s) in SpA are not known. Proteins such as collagen and proteoglycans have been thought to be potent autoantigens in arthritidis including B27-associated human diseases. Type II collagen is a common denominator among eyes and joints, affected tissues in B27-linked diseases. Moreover, a few reports indicated CII specific T cells and antibodies in patients with spondyloarthropathies. We and others have previously described development of spontaneous arthritis and nail disease in HLA-B27 transgenic animals. To determine whether CII may be a target antigen in the B27-linked diseases, B27 + m beta 2 m% (HLA-B27) transgenic mice lacking mouse beta 2m with and without human beta 2m) mice were immunized with type II collagen inside the barrier facility. Male HLA-B27 transgenic mice developed collagen-induced arthritis compared to transgene negative littermates or female counterparts. There was no difference in the incidence of arthritis in HLA-B27 transgenic mice with and without human beta 2m. Our data suggest that beta 2m free heavy chain of HLA-B27 may present soluble antigens such as type II collagen to trigger specific T cells contributing in the development of arthritis. Our data also suggest that CII may be a potential target antigen in the cartilage during the disease process.
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PMID:HLA-B27 transgenic mice are susceptible to collagen-induced arthritis: type II collagen as a potential target in human disease. 1071 6

There are many documented associations of the HLA B27-related diseases--the seronegative arthropathies (SNAs) and acute anterior uveitis (AAU). However, to date no single pathogenic mechanism has been proposed which can account for more than a few of these associations. The hypothesis presented in this paper is that individual inflammatory episodes in the SNAs and HLA B27 AAU are initiated locally within the inflamed site, in response to tiny quantities of innately recognised molecules--pathogen associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs). However, clinically significant responses to such small amounts of PAMPs/DAMPs only occur in those individuals who possess pre-existing tissue-specific autoreactive effector memory T-cells, which once recruited into the tissue where their autoantigen resides, can mediate inflammatory damage. The mechanism put forward here could explain much of the research evidence and distinguishing clinical features of the HLA B27-associated diseases. These include: the well documented involvement of micro-organisms and tissue damage in these diseases; the more frequent involvement of certain organs compared with others; the often local and asymmetrical presentation of the SNAs/AAU, which contrasts with other autoimmune diseases that effect many sites in a more diffuse/symmetrical pattern; the fact that these diseases which are thought to be mediated by T-cells, are nonetheless refractory to treatment with T-cell activation blockers. Finally, if correct, the mechanism would define a 5th type of clinical hypersensitivity reaction, one manifested by an excessive reaction to small pro-inflammatory signals, in individuals who possess tissue-specific autoreactive effector memory T-cells.
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PMID:A 5th type of hypersensitivity reaction: does incidental recruitment of autoreactive effector memory T-cells in response to minute amounts of PAMPs or DAMPs, underlie inflammatory episodes in the seronegative arthropathies and acute anterior uveitis? 1944 66