journal article
LitStream Collection
Home
Li, Xinjun; Sundquist, Jan; Sundquist, Kristina
doi: 10.1002/art.24526pmid: 19479884
Objective To examine whether there is an association between country of birth in first‐generation immigrants and first hospitalization for a rheumatic disease, and to study whether any such association remains in second‐generation immigrants. Methods In this followup study, the Swedish MigMed database at the Karolinska Institute in Stockholm was used to identify all primary hospital diagnoses of rheumatic diseases in first‐ and second‐generation immigrants in Sweden between January 1, 1964 and December 31, 2004. Incidence ratios, standardized with regard to age, geographic region, and socioeconomic status, were estimated by sex in first‐ and second‐generation immigrants. Results First‐generation immigrants from Iraq had a higher risk of rheumatoid arthritis than did subjects in the native‐born Swede reference group, and the risk of systemic lupus erythematosus was increased in immigrants from Iraq and Africa; these raised risks persisted in the second generation. The lower risk of rheumatoid arthritis in some first‐generation immigrants disappeared in the second generation. In groups of second‐generation immigrants, the risk of ankylosing spondylitis was similar to the risk in the corresponding parental groups. Polish‐born immigrants and second‐generation Yugoslavs and Russians showed a significantly increased risk of systemic sclerosis. The raised risk of systemic sclerosis did not persist in the second generation, but was clustered in groups involved in certain blue collar occupations. Conclusion Country of birth affected the risk of rheumatic disease. These findings indicate that both genetic and environmental factors are involved in the etiology of specific rheumatic diseases.
Lundström, Emeli; Källberg, Henrik; Alfredsson, Lars; Klareskog, Lars; Padyukov, Leonid
doi: 10.1002/art.24572pmid: 19479873
Objective An interaction effect for developing rheumatoid arthritis (RA) was previously observed between HLA–DRB1 shared epitope (SE) alleles and smoking. We aimed to further investigate this interaction between distinct SE alleles and smoking regarding the risk of developing RA with and without anti–citrullinated protein antibodies (ACPAs). Methods We used data regarding smoking habits and HLA–DRB1 genotypes from 1,319 patients and 943 controls from the Epidemiological Investigation of Rheumatoid Arthritis, in which 972 patients and 488 controls were SE positive. Subsequently, 759 patients and 328 controls were subtyped for specific alleles within the DRB1*04 group. Odds ratios with 95% confidence intervals (95% CIs) were calculated by means of logistic regression. Interaction was evaluated by calculating attributable proportion due to interaction, with 95% CIs. Results A strong interaction between smoking and SE alleles in the development of ACPA‐positive RA was observed for all DRB1*04 SE alleles taken as a group (relative risk (RR) 8.7 (95% CI 5.7–13.1)) and for the *0401 and *0404 alleles (RR 8.9 (95% CI 5.8–13.5)) and the *01 and *10 alleles (RR 4.9 (95% CI 3.0–7.8)) as specific, separate groups, with similar strength of interaction for the different groups (attributable proportion due to interaction 0.4 (95% CI 0.2–0.6), 0.5 (95% CI 0.3–0.7), and 0.6 (95% CI 0.4–0.8), respectively). Conclusion There is a statistically significant interaction between distinct DRB1 SE alleles and smoking in the development of ACPA‐positive RA. Interaction occurs with the *04 group as well as the *01/*10 group, demonstrating that regardless of fine specificity, all SE alleles strongly interact with smoking in conferring an increased risk of ACPA‐positive RA.
Filer, Andrew; Bik, Magdalena; Parsonage, Greg N.; Fitton, John; Trebilcock, Emily; Howlett, Katherine; Cook, Michelle; Raza, Karim; Simmons, David L.; Thomas, Andrew M. C.; Salmon, Mike; Scheel‐Toellner, Dagmar; Lord, Janet M.; Rabinovich, Gabriel A.;
Showing 1 to 10 of 44 Articles
doi: 10.1002/art.24574pmid: 19479862
Objective High expression of galectin 3 at sites of joint destruction in rheumatoid arthritis (RA) suggests that galectin 3 plays a role in RA pathogenesis. Previous studies have demonstrated the effects of galectins on immune cells, such as lymphocytes and macrophages. This study was undertaken to investigate the hypothesis that galectin 3 induces proinflammatory effects in RA by modulating the pattern of cytokine and chemokine production in synovial fibroblasts. Methods Matched samples of RA synovial and skin fibroblasts were pretreated with galectin 3 or tumor necrosis factor α (TNFα), and the levels of a panel of cytokines, chemokines, and matrix metalloproteinases (MMPs) were determined using enzyme‐linked immunosorbent assays and multiplex assays. Specific inhibitors were used to dissect signaling pathways, which were confirmed by Western blotting and NF‐κB activation assay. Results Galectin 3 induced secretion of interleukin‐6 (IL‐6), granulocyte–macrophage colony‐stimulating factor, CXCL8, and MMP‐3 in both synovial and skin fibroblasts. By contrast, galectin 3–induced secretion of TNFα, CCL2, CCL3, and CCL5 was significantly greater in synovial fibroblasts than in skin fibroblasts. TNFα blockade ruled out autocrine TNFα‐stimulated induction of chemokines. The MAPKs p38, JNK, and ERK were necessary for IL‐6 production, but phosphatidylinositol 3‐kinase (PI 3‐kinase) was required for selective CCL5 induction. NF‐κB activation was required for production of both IL‐6 and CCL5. Conclusion Our findings indicate that galectin 3 promotes proinflammatory cytokine secretion by tissue fibroblasts. However, galectin 3 induces the production of mononuclear cell–recruiting chemokines uniquely from synovial fibroblasts, but not matched skin fibroblasts, via a PI 3‐kinase signaling pathway. These data provide further evidence of the role of synovial fibroblasts in regulating the pattern and persistence of the inflammatory infiltrate in RA and suggest a new and important functional consequence of the observed high expression of galectin 3 in the rheumatoid synovium.