排序方式: 共有52条查询结果,搜索用时 28 毫秒
21.
Lars Klareskog Patrik Stolt Karin Lundberg Henrik Kllberg Camilla Bengtsson Johan Grunewald Johan Rnnelid Helena Erlandsson Harris Ann‐Kristin Ulfgren Solbritt Rantap‐Dahlqvist Anders Eklund Leonid Padyukov Lars Alfredsson 《Arthritis \u0026amp; Rheumatology》2006,54(1):38-46
Objective
To investigate whether smoking and HLA–DR shared epitope (SE) genes may interact in triggering immune reactions to citrulline‐modified proteins.Methods
In a case–control study involving patients with recent‐onset rheumatoid arthritis (RA), we studied interactions between a major environmental risk factor (smoking), major susceptibility genes included in the SE of HLA–DR, and the presence of the most specific autoimmunity known for RA (i.e., antibodies to proteins modified by citrullination). Immunostaining for citrullinated proteins in cells from bronchoalveolar lavage fluid was used to investigate whether smoking is associated with citrullination in the lungs.Results
Previous smoking was dose‐dependently associated with occurrence of anticitrulline antibodies in RA patients. The presence of SE genes was a risk factor only for anticitrulline‐positive RA, and not for anticitrulline‐negative RA. A major gene–environment interaction between smoking and HLA–DR SE genes was evident for anticitrulline‐positive RA, but not for anticitrulline‐negative RA, and the combination of smoking history and the presence of double copies of HLA–DR SE genes increased the risk for RA 21‐fold compared with the risk among nonsmokers carrying no SE genes. Positive immunostaining for citrullinated proteins was recorded in bronchoalveolar lavage cells from smokers but not in those from nonsmokers.Conclusion
We identified an environmental factor, smoking, that in the context of HLA–DR SE genes may trigger RA‐specific immune reactions to citrullinated proteins. These data thus suggest an etiology involving a specific genotype, an environmental provocation, and the induction of specific autoimmunity, all restricted to a distinct subset of RA.22.
Ärlestig L Mullazehi M Kokkonen H Rocklöv J Rönnelid J Dahlqvist SR 《Annals of the rheumatic diseases》2012,71(6):825-829
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The cholinergic anti-inflammatory pathway is a newly discovered pathway. Another recent concept is the existence of a non-neuronal cholinergic system that has, so far, been defined for human tendons, intestine, airways and urinary bladder. The existence of such a system in joint synovial tissue is yet to be described. We therefore aimed to investigate the expression of choline acetyltransferase (ChAT) at both the protein and mRNA level using immunohistochemistry and in situ hybridisation, in human knee synovial tissue from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. The biopsy samples were collected from patients undergoing knee prosthetic surgery. Our results show that both ChAT protein and mRNA is expressed in fibroblast-like and mononuclear-like cells, and to some extent in blood vessel walls in the synovial tissue. The mononuclear-like cells showing ChAT expression were scattered throughout the synovial tissue or located in association with lymphoid aggregates. Thus, we present the first evidence of the existence of a marked non-neuronal cholinergic system in human synovial tissue. The existence of this system could lead to the development of alternative medications to those currently in use. The system might function as a cholinergic anti-inflammatory pathway in synovial tissue. Our observations show that synovial tissue of patients with marked RA or OA, a tissue in which cholinergic innervation is not proven to exist, is supplied with acetylcholine via production in non-neuronal cells within the tissue. 相似文献
25.
Hom G Graham RR Modrek B Taylor KE Ortmann W Garnier S Lee AT Chung SA Ferreira RC Pant PV Ballinger DG Kosoy R Demirci FY Kamboh MI Kao AH Tian C Gunnarsson I Bengtsson AA Rantapää-Dahlqvist S Petri M Manzi S Seldin MF Rönnblom L Syvänen AC Criswell LA Gregersen PK Behrens TW 《The New England journal of medicine》2008,358(9):900-909
26.
Innala L Kokkonen H Eriksson C Jidell E Berglin E Dahlqvst SR 《The Journal of rheumatology》2008,35(6):1002-1008
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28.
Paul G. Green Solbritt Rantapää Dahlqvist William M. Isenberg Frederick J.-P. Miao Jon D. Levine 《The European journal of neuroscience》2001,14(9):1436-1444
Many inflammatory diseases show a female predilection in adults, but not prepubertally. Because sex differences in the inflammatory response in the adult rat are mediated, in part, by sexual dimorphism in adrenal medullary function, we investigated the contribution of the adrenal medulla to the ontogeny of sexual dimorphism in inflammation. Whilst there was no sex difference in the magnitude of the plasma extravasation (PE) induced by the potent inflammatory mediator bradykinin (BK) in prepubertal rats, in adult rats BK-induced PE was markedly greater in males. Also, adult male rats, gonadectomized prior to puberty, had a lower magnitude of BK-induced PE than did adult male controls, whilst adult females gonadectomized prepubertally had higher BK-induced PE than did controls. In rats gonadectomized after puberty, the magnitude of BK-induced PE in adult males was not affected, whilst in females it resulted in significantly higher BK-induced PE, similar to the effect of prepubertal gonadectomy. When tested prepubertally, adrenal denervation increased the magnitude of BK-induced PE in females, but not in males. In contrast, in both males and females tested as adults, but castrated prepubertally, and in gonad-intact adult females, adrenal denervation significantly increased the magnitude of BK-induced PE. Adrenal denervation in prepubertal females given adult levels of 17beta-oestradiol produced a marked enhancement in the denervation-induced increase in magnitude of BK-induced PE compared to females not exposed prematurely to sex hormones. These studies suggest that an adrenal medulla-dependent inhibition of BK-induced PE is present in female but not male rats, and is enhanced by oestrogen but suppressed by testosterone. 相似文献
29.
Andersen GN Nilsson K Pourazar J Hackett TL Kazzam E Blomberg A Waldenström A Warner J Rantapää-Dahlqvist S Mincheva-Nilsson L Sandström T 《Respiratory medicine》2007,101(10):2199-2206
Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition. 相似文献
30.
Johan Askling Ronald F. van Vollenhoven Fredrik Granath Pauline Raaschou C. Michael Fored Eva Baecklund Christina Dackhammar Nils Feltelius Lars Cster Pierre Geborek Lennart T. Jacobsson Staffan Lindblad Solbritt Rantap‐Dahlqvist Tore Saxne Lars Klareskog 《Arthritis \u0026amp; Rheumatology》2009,60(11):3180-3189