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Objective. Early recognition and treatment of RA is associated with an improved outcome. The 2010 ACR/EULAR criteria for RA identify RA patients earlier than the 1987 ACR criteria. Nevertheless, we recently observed that 24% of the 2010 unclassified arthritis (UA) patients develop RA during follow-up. Here we studied this frequency in other cohorts and evaluated the prognostic accuracy of ACPA and the Leiden prediction rule in 2010 UA patients.Methods. The 2010 UA patients from three Early Arthritis Clinics were studied: 776 from Leiden, 121 from Birmingham and 322 from Amsterdam. Fulfilment of the 1987 ACR criteria during follow-up was studied as the primary outcome. DMARD prescription during the year and having a persistent course of arthritis over 7 years were studied as secondary outcomes in one cohort. The presence of ACPA and the prediction score at baseline were evaluated in relation to these outcomes.Results. In the three cohorts, 24%, 26% and 12%, respectively, of the 2010 UA patients fulfilled the 1987 criteria after 1 year. However, some of these patients already fulfilled the 1987 criteria at baseline. In 1987 and 2010 UA patients, 15%, 21% and 9%, respectively, developed RA (1987) at 1 year. In these patients, 0–6% of the patients were ACPA positive and 0–1% had high prediction scores. Consequently a large majority of the UA patients with an unfavourable outcome was not recognized by these prognostic tools.Conclusion. A proportion of 2010 UA patients progress to RA. ACPA and the Leiden prediction rule are not useful in identifying these patients. These results imply that other predictive markers should be developed for 2010 UA patients. [ABSTRACT FROM PUBLISHER]

Objective Genetic factors account for an estimated 45-58% of the variance in joint destruction in rheumatoid arthritis (RA). The serine proteinase granzyme B induces target cell apoptosis, and several in vitro studies suggest that granzyme B is involved in apoptosis of chondrocytes. Serum levels of granzyme B are increased in RA and are also associated with radiographic erosions. The aim of this study was to investigate GZMB as a candidate gene accounting for the severity of joint destruction in RA. Methods A total of 1,418 patients with 4,885 radiograph sets of the hands and feet from 4 independent cohorts were studied. First, explorative analyses were performed in 600 RA patients in the Leiden Early Arthritis Clinic cohort. Fifteen single-nucleotide polymorphisms (SNPs) tagging GZMB were tested. Significantly associated SNPs were genotyped in data sets representing patients from the Groningen, Sheffield, and Lund cohorts. In each data set, the relative increase in the annual rate of progression in the presence of a genotype was assessed. Data were summarized in a meta-analysis. The association of GZMB with the RNA expression level of the GZMB genomic region was tested by mapping expression quantitative trait loci (QTLs) on 1,469 whole blood samples . Results SNP rs8192916 was significantly associated with the rate of joint destruction in the first cohort and in the meta-analysis of all data sets. Patients homozygous for the minor allele of rs8192916 had a higher rate of joint destruction per year compared with other patients ( P = 7.8 × 10−4). Expression QTL of GZMB identified higher expression in the presence of the minor allele of rs8192916 ( P = 2.27 × 10−5). Conclusion SNP rs8192916 located in GZMB is associated with the progression of joint destruction in RA as well as with RNA expression in whole blood. [ABSTRACT FROM AUTHOR]