OBJECTIVE: Only 31% of Dutch rheumatoid arthritis (RA)-patients visit a rheumatologist within 12 weeks after symptom onset; this is mainly due to delay at the level of the general practitioner (GP)... Show moreOBJECTIVE: Only 31% of Dutch rheumatoid arthritis (RA)-patients visit a rheumatologist within 12 weeks after symptom onset; this is mainly due to delay at the level of the general practitioner (GP). In order to reduce delay of GPs in identifying early arthritis, we initiated an Early Arthritis Recognition Clinic (EARC). METHODS: EARCs were initiated at the Leiden and Groningen University Medical Centers. At this EARC, patients filled in a questionnaire about their symptoms, followed by a short visit with only a full joint examination by an experienced rheumatologist. If arthritis was present the patient got an appointment the same week at the regular outpatient clinic. The main outcome parameter was the GP-delay; the secondary outcome parameter was the total delay. In both centres, patients included in early arthritis clinics that had arrived via regular referrals served as control group. RESULTS: Four hundred patients visited the Leiden EARC and 212 patients the Groningen EARC. Arthritis was detected in 42% and 49% respectively. The median GP-delay for these arthritis patients was 2.0 (0.4-7.3) and 2.0 (0.4-10.0) weeks and the median total delay 8.6 (3.6-22.3) and 10.6 (3.1-30.8) weeks respectively. At these two clinics 59% and 51% of all arthritis patients and 65% and 53% of the patients that were subsequently diagnosed with undifferentiated arthritis or RA were seen within 12 weeks after symptom onset. In the Leiden and Groningen control groups that arrived via regular referrals, only 32% and 38% were seen within 12 weeks time. CONCLUSIONS: The EARC increased the early identification of arthritis and RA. Show less
Hunt, K.A.; Smyth, D.J.; Balschun, T.; Ban, M.; Mistry, V.; Ahmad, T.; ... ; Wellcome Trust Case 2012
Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored.... Show moreEpidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P < 5 x 10(-8) in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P-combined = 1.2 x 10(-12)), rs864537 near CD247 (P-combined = 2.2 x 10(-11)), rs2298428 near UBE2L3 (P-combined = 2.5 x 10(-10)), and rs11203203 near UBASH3A (P-combined = 1.1 x 10(-8)). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5 x 10(-8) (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases. Show less
To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases... Show moreTo identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles. Show less
