Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms (SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes--the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes--we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P<10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system.
Despite early pacing, CHB carries high mortality during the first 12 months of life. High incidences of DCM and associated heart defects indicate close echocardiographic monitoring of all children with CHB.
Objective. To compare the efficacy of therapy with a combination of disease-modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA).Methods. In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recentonset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination-treatment group and 82 in the singletreatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA-related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age.Results. The cumulative duration of work disability per patient-observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0-54) versus 32.2 days (IQR 6-293) (P ؍ 0.008, sex-and age-adjusted P ؍ 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods <300 days): median 11.7 days (IQR 0-44) per patient-observation year in those treated with combination therapy and 30.0 days (IQR 6-68) in those treated with single therapy (P ؍ 0.002). No statistically significant difference was seen in RArelated disability pensions.Conclusion. Aggressive initial treatment of RA with a combination of DMARDs improves 5-year outcome in terms of lost productivity in patients with RA of recent onset.Loss of ability to work is a frequent and serious outcome of rheumatoid arthritis (RA) (1-14), accounting for a large proportion of the costs of this disease (15,16). Cessation of working life results from interactions between various physiologic variables, social conditions, and work-related factors. Several studies have indicated that physically demanding jobs, lower educaSupported by the medical research foundations of Lappeenranta Central Hospital and the Rheumatism Foundation Hospital. 1
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