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- Holmdahl, Rikard
(författare)
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Primer: comparative genetics of animal models of arthritis--a tool to resolve complexity.
- 2007
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Ingår i: Nature Clinical Practice Rheumatology. - : Springer Science and Business Media LLC. - 1745-8382 .- 1745-8390. ; 3:2, s. 104-111
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Forskningsöversikt (refereegranskat)abstract
- Complex traits, including inflammatory rheumatic diseases, have important genetic features, but most of the responsible genes have not been conclusively identified. Genetic analysis of inbred animal models and comparative genetics - the comparison of genes between different species - might help to identify the crucial genes and to investigate more directly the biology involved. Genome-wide linkage analysis of particular genes can be assessed by genetic segregation studies, whereas disease pathways can be delineated by the use of congenic strains. To clone disease genes, the traits need to be transformed so that they are inherited in a more Mendelian manner: achieving this pattern requires isolation of the locus on a genetic background that allows high penetrance by minimization of the size of congenic fragments, genetic manipulations without associated artifacts, or identification of highly penetrant mutations by phenotypic selection. Although almost one hundred quantitative trait loci for arthritis have been identified, only a few genes have so far been positionally cloned. In this Review we highlight the possibilities of using animal models to identify genes associated with complex diseases like arthritis, illustrated with available findings for genes such as those encoding major histocompatibility complex class II, neutrophil cytosolic factor 1 (Ncf1/p47(phox)) and ZAP70.
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- Nordmark, Gunnel, et al.
(författare)
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Mechanisms of Disease : primary Sjögren's syndrome and the type I interferon system
- 2006
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Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1745-8382. ; 2:5, s. 262-269
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Tidskriftsartikel (refereegranskat)abstract
- Sjögren's syndrome is a chronic autoimmune disease of largely unknown etiology and pathogenesis. The salivary and lacrimal glands are the main target organs, and key cells and molecules involved in the autoimmune process have been detected in these glands. Chemokines, expressed by epithelial cells, can attract T cells and dendritic cells that produce proinflammatory cytokines, which stimulate the immune response and induce apoptosis in the acinar and ductal epithelial cells. The autoantigens SSA and SSB are translocated to the apoptotic blebs and trigger infiltrating B cells to produce autoantibodies against SSA and SSB. Germinal-center-like structures can form within glandular lymphocyte foci, facilitating the antigen-driven B-cell activation. Many of the autoimmune mechanisms described above can be induced by type I interferon (IFN), and activation of this system in patients with Sjögren's syndrome has been described. A possible scenario is that an initial viral infection induces type I IFN production in salivary glands with a subsequent activation of the adaptive immune system. Resultant autoantibodies form nucleic-acid-containing immune complexes that can trigger prolonged type I IFN production, leading to a self-perpetuating autoimmune reaction. Several potential therapeutic targets for Sjögren's syndrome exist within the type I IFN system.
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- Woolf, Anthony D, et al.
(författare)
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Primer: history and examination in the assessment of musculoskeletal problems
- 2008
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Ingår i: Nature Clinical Practice Rheumatology. - : Springer Science and Business Media LLC. - 1745-8382 .- 1745-8390. ; 4:1, s. 26-33
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Forskningsöversikt (refereegranskat)abstract
- Musculoskeletal problems are very common, and clinical assessment is central to their appropriate management; however, many clinicians are not sufficiently competent to carry out this assessment. A standardized approach to the clinical assessment of a musculoskeletal problem is, therefore, necessary, whether the patient is presenting to primary care, rheumatology or orthopedics. Such a standardized approach gives a benchmark for this competency and can also be used as a teaching aid. As doctors become increasingly competent in clinical assessment and reach into training programs within musculoskeletal specialities, more detailed information will be required from the medical history of the patient, in addition to the use of special tests on clinical examination. These clinical skills need to be taught and also assessed.
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