Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is convincing evidence of a genetic basis for both psoriasis and psoriatic arthritis (PsA). Part of this genetic predisposition is due to genes within the major histocompatibility complex (MHC). In psoriasis, the primary association is with HLA-Cw6. Further work on specific nucleotide frequencies, especially those in the alpha 1 domain helix of the HLA-C molecule, will be of interest in determining whether a specific nucleotide frequency is present in all patients. The situation in PsA is considerably more complex. It is now established that there is an association between HLA-B27 and PsA, both in its peripheral arthropathy and in spinal disease in which radiological sacroiliitis is present. Spinal disease without radiological sacroiliitis is probably not associated with HLA-B27. There is some suggestion that HLA-B16 or its splits, HLA-B38 and HLA-B39, may also be associated with PsA, but there is considerable heterogeneity between the series, which prevents a firm conclusion being made. It is possible, but again not conclusive, that there is an association between HLA-DR4 and the symmetrical seronegative pattern of peripheral PsA. It is also likely that genes outwith the MHC predispose to psoriasis and PsA. It is further likely that a role will be found for environmental factors in both psoriasis and PsA. There is a tantalizing possibility of a complex interplay between a variety of environmental factors and genetic factors, both within and outwith the MHC, determining not only susceptibility but also the individual clinical pattern of disease. Further clarification of these possibilities is likely to depend primarily on understanding the role of genes within the MHC in predisposing to comparatively more homogeneous diseases, such as psoriasis and ankylosing spondylitis, before the mechanisms operating in PsA can be analysed and better understood.
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PMID:Psoriatic arthritis. Genetics and HLA antigens. 807 87

The nucleotide-binding domain, leucine-rich repeat containing family (NLR) network has provided pivotal genetic and molecular insights into diseases that were hitherto regarded as autoimmune. The NLR-related disorders include rare monogenic autoinflammatory diseases collectively termed cryopyrin-associated periodic syndromes, Crohn's disease which is a common polygenic disease and also an association at the mechanistic level with gout and pseudogout. Unlike the classical autoimmune diseases where disease immunopathogenesis is played out primarily in the primary and secondary lymphoid organs, the immunopathogenesis of the NLR-related disorders is played out in the tissues where inflammation arises. As the genetic mutations or molecular cascades associated with the NLR-related disorders have a widespread cellular distribution, it has been somewhat enigmatic why these disorders attack certain territories, but not others. This implies that tissue-specific factors in the target organs themselves contribute to disease expression. Such examples include the high abundance of NOD2 expressing cells in the part of the gut most typically afflicted by Crohn's disease and the preferential deposition of crystals in the joints to where inflammation localises in gout and pseudogout. The NLR network is associated principally with increases in TNF or IL-1 production, both of which are key players in innate immunity. Therefore, the NLR network identifies at the genetic and molecular level a robust paradigm for innate immune activation against self. This tissue-specific-factor-associated inflammation is the diametric opposite of classical autoimmunity. Of note, the MHC class-I-associated diseases including psoriasis (HLA-Cw6) and ankylosing spondylitis (HLA-B27) show striking clinical overlaps with Crohn's disease and also some rare monogenic diseases. Thus, the NLR innate immune pathway allows the full spectrum of inflammation against self to be viewed along an immunological disease continuum with autoantibody-associated disease at one end, innate immune diseases at the other and MHC class-1-related disorders as an intermediate.
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PMID:The NLR network and the immunological disease continuum of adaptive and innate immune-mediated inflammation against self. 1780 42