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- Klareskog, Lars, et al.
(författare)
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Antibodies to citrullinated proteins in arthritis : pathology and promise
- 2008
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Ingår i: Current Opinion in Rheumatology. - 1040-8711 .- 1531-6963. ; 20:3, s. 300-305
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: The purpose of this review is to describe how the current knowledge of antibodies to citrullinated protein antigens in rheumatoid arthritis and related conditions emerged; to discuss the diagnostic and prognostic value associated with antibodies to citrullinated protein antigens as a biomarker; and most importantly for this review, to discuss the potential pathogenetic significance of these antibodies. RECENT FINDINGS: Antibodies to citrullinated protein antigens have evolved from being mainly a diagnostic marker, to being recognized as something that can help us understand fundamental etiologic and pathogenetic features of rheumatoid arthritis. Fundamental in this context is the finding that rheumatoid arthritis can be divided into two distinct subsets by means of presence or absence of antibodies to citrullinated protein antigens. Thus, several genetic as well as environmental risk factors differ between these two variants of rheumatoid arthritis. From analysis of these genetic and environmental risk factors, new testable hypotheses have been produced concerning triggering of antibodies to citrullinated protein antigens, and potential pathogenicity of antibodies to citrullinated protein antigens and accompanying immune reactions. SUMMARY: The implications of the findings are that antibodies to citrullinated protein antigens can be used for early and precise diagnosis of a subset of rheumatoid arthritis with worse prognosis than other polyarthritides, and that a new basis is formed for etiologic and pathogenetic studies of antibodies to citrullinated protein antigens-positive rheumatoid arthritis.
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| 2. |
- Rantapää-Dahlqvist, Solbritt, 1947-
(författare)
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What happens before the onset of rheumatoid arthritis?
- 2009
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Ingår i: Current Opinion in Rheumatology. - : Lippincott Williams & Wilkins, Inc. - 1040-8711 .- 1531-6963. ; 21:3, s. 272-278
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: To give an overview of publications on presence of autoantibodies, rheumatoid factor and anticitrullinated protein/peptide antibodies (ACPAs) and their relationships to genetic markers and soluble factors as indicators of immune activation and identified predating the onset of symptoms of rheumatoid arthritis (RA). RECENT FINDINGS: The development during recent years concerning autoantibodies with high specificity for RA, ACPAs, has confirmed previous findings of presence of autoantibodies, such as rheumatoid factors and antikeratin antibodies, years before disease onset. Particularly, ACPAs in combination with human leukocyte antigen-shared epitope alleles and PTPN22 1858T carriage increased the relative risks of developing RA compared with not having these factors. Both shared epitope alleles and 1858T variant seemed to contribute to development of ACPAs rather than independently contribute to RA. Soluble factors such as hypersensitive C-reactive protein, cytokines, cytokine receptors and chemokines are upregulated before disease onset, though, not as long antedating time as ACPAs and rheumatoid factors. SUMMARY: Presence of ACPAs and rheumatoid factors are present several years before disease onset suggesting a gradual process leading to the development of RA. Genetic markers such as shared epitope alleles and PTPN22 1858T variant increase the relative risk for disease development. Soluble immunological markers are also increased closer to the onset of symptoms indicating activation of the immune system.
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| 3. |
- Rönnblom, Lars, et al.
(författare)
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Type I interferon and lupus
- 2009
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Ingår i: Current Opinion in Rheumatology. - 1040-8711 .- 1531-6963. ; 21:5, s. 471-477
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: Patients with lupus have signs of an ongoing production of type I interferons (IFNs) that are of importance both for the etiopathogenesis and the clinical manifestations. In this review, we summarize the latest information concerning the type I IFN system in lupus. RECENT FINDINGS: Activated plasmacytoid dendritic cells are responsible for the IFNalpha production in lupus and can be found in target organs such as glomeruli. The plasmacytoid dendritic cells are triggered by interferogenic immune complexes, and produced IFNalpha activates the immune system and impairs T-regulatory cell function. Autoantibodies, which can form interferogenic immune complexes, are not only present in serum of lupus patients but also in the cerebrospinal fluid of patients with neuropsychiatric manifestations. There is a strong association between risk to develop lupus and gene variants connected to the production and effects of type I IFN. Risk variants can not only cause either increased serum IFNalpha activity or sensitivity but also a more severe disease phenotype. Administration of monoclonal anti-IFNalpha antibodies to lupus patients downregulates several proinflammatory pathways and reduces disease activity. SUMMARY: Increasing evidence indicates that the activated type I IFN system in lupus is critical in the etiopathogenesis of the disease and is an important therapeutic target.
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| 15. |
- Segelmark, Mårten, et al.
(författare)
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The challenge of managing patients with polyarteritis nodosa.
- 2007
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Ingår i: Current Opinion in Rheumatology. - 1531-6963. ; 19:1, s. 33-38
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review In this short review we focus on the problems faced by clinicians caused by the changing definitions of polyarteritis nodosa. Recent findings the term polyarteritis nodosa has been used for more than 100 years as a diagnostic term for patients with systemic vasculitis, however, specific vasculitides have been singled out like branches being chopped off a tree. Now, so little is left of the trunk of that tree that it is questionable to what extent we can trust older literature with respect to clinical features, natural history and response to treatment. Many authors of case reports, as well as authors of reviews and book chapters, claim they adhere to the Chapel Hill Consensus Conference definition of polyartentis nodosa yet still cite almost exclusively studies using older definitions without highlighting this dilemma. In the past year, two proposals affecting classification have been published: one stating that cutaneous polyarteritis nodosa and hepatitis associated polyarteritis nodosa, and one providing an algorithm to separate microscopic polyangiitis from classical polyarteritis nodosa. Summary There is hope that a wide acceptance of the new classification principles will lead to a more uniform way to diagnose classical polyarteritis nodosa, which will facilitate clinical studies and eventually improve management.
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| 16. |
- Strömbeck, Britta, et al.
(författare)
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The role of exercise in the rehabilitation of patients with systemic lupus erythematosus and patients with primary Sjögren's syndrome.
- 2007
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Ingår i: Current Opinion in Rheumatology. - 1531-6963. ; 19:2, s. 197-203
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review: The purpose of this review is to present an update on the evidence-based effects of exercise in systemic lupus erythematosus and in primary Sjögren's syndrome. Recent findings: Physical capacity is reduced in both systemic lupus erythematosus and primary Sjögren's syndrome and fatigue is a dominating and disabling symptom in both conditions. The documentation on the effect of exercise on the rehabilitation of patients with systemic lupus erythematosus and primary Sjögren's syndrome is sparse; the studies are few and the sample sizes often small. The available studies indicate that patients with systemic lupus erythematosus of mild to moderate disease activity as well as patients with primary Sjögren's syndrome benefit from exercise of moderate to high intensity. Positive effects can be expected with regard to aerobic capacity, fatigue, physical function and depression. Summary: There is reason to believe that exercise should be included in the rehabilitation of patients with mild to moderate systemic lupus erythematosus and patients with primary Sjögren's syndrome. Further research is needed and should aim to evaluate the effect of exercise on groups with varying degree of disease severity and to document the long-term impact on the disease.
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| 17. |
- Turesson, Carl, et al.
(författare)
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Cardiovascular risk factors, fitness and physical activity in rheumatic diseases.
- 2007
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Ingår i: Current Opinion in Rheumatology. - 1531-6963. ; 19:2, s. 190-196
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review There is increased recognition of an excess risk of cardiovascular disease in patients with rheumatic disorders. Physical inactivity is a frequent complication of arthritis, and also common in the general population. In this review, we highlight recent findings on risk factors for cardiovascular disease in patients with rheumatic diseases, and explore the role of physical activity for the prevention of cardiovascular disease. Recent findings Inflammatory mechanisms are clearly involved in cardiovascular disease in patients with systemic lupus erythematosus and rheumatoid arthritis. In rheumatoid arthritis, disability is also a major predictor of cardiovascular disease. A sedentary lifestyle increases the risk of cardiovascular disease in the general population, and high physical activity prevents cardiovascular disease mortality and morbidity. Successful treatment of rheumatic disease with control of inflammation and improved functional capacity may also reduce the risk of cardiovascular disease. Summary As part of the effort to prevent vascular comorbidity, regular exercise should be encouraged in patients with rheumatic diseases, and structured interventions to reduce adverse lifestyle factors scientifically evaluated.
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| 18. |
- Turesson, Carl, et al.
(författare)
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Vasculitis in rheumatoid arthritis.
- 2009
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Ingår i: Current Opinion in Rheumatology. - 1531-6963. ; 21:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: To examine the occurrence and pathophysiology of vasculitis in rheumatoid arthritis (RA), describe the epidemiology and clinical features, and provide a therapeutic perspective. RECENT FINDINGS: With improved control of RA over the past two decades, the risk of severe outcomes such as vasculitis may be decreasing. Rheumatoid vasculitis continues to be associated with longstanding, erosive, seropositive disease, and it has recently been shown to be more frequent among patients with antibodies to cyclic citrullinated peptides. Apart from circulating immune complexes, expansion of cytotoxic CD28null T cells and circulating proinflammatory cytokines also play a role in the pathogenesis. The role of agents directed against the tumor necrosis factor (TNF) in the occurrence and management of rheumatoid vasculitis remains unclear, as rheumatoid vasculitis may be both associated with and treated with anti-TNF agents, once it has appeared. SUMMARY: Vasculitis in RA is generally associated with longstanding disease, has an important impact on a patient's well being, and markedly influences patient life expectancy. Advances in therapies for RA will likely continue to reduce the incidence of vasculitis, and improved management of cardiovascular comorbidity in patients with RA will be of particular benefit to those who suffer from vasculitis and other extraarticular manifestations.
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