The new 2010 ACR/EULAR criteria as predictor of clinical and radiographic response in patients with early arthritis.

New American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for the classification of rheumatoid arthritis (RA) have recently been proposed. The aim of this cohort study was to examine whether fulfilling these 2010 ACR/EULAR criteria at the first visit has an impact on the clinical course and on the radiographic progression of the disease. For this observational cohort study, we included patients from the Swiss RA registry SCQM with early RA or undifferentiated arthritis (UA, disease duration ≤1 year), as defined by the treating rheumatologist, who had not received any previous disease modifying anti-rheumatic drugs (DMARDs). Patients were categorized into two groups depending on whether or not they fulfilled the 2010 ACR/EULAR criteria (≥6 points vs <6 points) at the first visit. The primary outcome measures were the evolution of the DAS 28 and of radiographic erosions as measured by the Ratingen score over time. Of the 592 patients fulfilling the inclusion criteria, 352 satisfied the 2010 ACR/EULAR criteria at baseline, whereas 240 were not classifiable as definite RA. The ACR/EULAR criteria scores correlated with disease activity at disease onset (R (2) = 0.31). DMARD treatment was subsequently initiated in all patients, mostly with methotrexate (MTX). There were no significant differences in the therapeutic strategies between patients fulfilling or not fulfilling the classification criteria. Six months after inclusion, patients fulfilling the ACR/EULAR criteria developed a 39.1 % reduction of DAS 28 scores, as compared to a 33.6 % reduction in patients not fulfilling the ACR/EULAR criteria (p = 0.0002), independently of their respective treatment strategy. Importantly, the DAS 28 scores were higher in those patients fulfilling the ACR/EULAR criteria (ACR/EULAR positive patients) throughout the observation, as compared to patients not fulfilling those (ACR/EULAR negative patients). Average radiographic progression was higher among ACR/EULAR positive than negative patients (progression of Ratingen score/year 0.50 vs 0.32, resp., p = 0.03) after 3 years of follow-up. Among early RA/UA patients, a score of the 2010 ACR/EULAR criteria sufficient to classify RA selects patients with worse clinical outcome and more radiographic progression.

MHC class II expression on myeloid cells inversely correlates with disease progression in early rheumatoid arthritis.

OBJECTIVE: To investigate whether MHC class II expression on myeloid cells of patients with treatment-naive early rheumatoid arthritis (RA) correlates with disease progression. METHODS: Monocytes were isolated by negative selection from the peripheral blood of 15 patients with early RA (disease duration < or =12 months), differentiated to macrophages and analysed for MHC class II expression by flowcytometry. The phenotypical data were correlated with clinical disease progression for up to 45 months. RESULTS: Before treatment was initiated, in vitro differentiated macrophages of 10/15 early RA patients expressed MHC class II comparable with macrophages from healthy controls. In sharp contrast, macrophages of the remaining five patients expressed significantly fewer MHC class II molecules. In contrast to patients with normal levels of myeloid cell MHC class II expression, who developed a smouldering, non-progressive disease, patients with decreased expression of MHC class II on macrophages early in their disease developed a continuously active disease as demonstrated by persistently increased disease activity scores (chi(2) = 4.54, P < 0.02) and progressive bone destructions (chi(2) = 5.66, P < 0.02) despite aggressive therapy. CONCLUSION: The level of myeloid cell MHC class II expression in recent onset RA allows a reliable distinction between patients who develop active and destructive RA and patients with a smouldering, slowly progressive disease.

Metabolism of delta24-sterols by yeast mutants blocked in removal of the C-14 methyl group.

We have investigated the metabolism of exogenously provided delta24-sterols by whole cell cultures of a polyene-resistant mutant (D10) of Candida albicans blocked at removal of the C-14 methyl group. Comparison of the relative efficiencies of transmethylation at C-24 of selected sterol substrates revealed the following substrate preferences of the Candida delta24-sterol methyltransferase (EC 2.1.1.41): zymosterol greater than 4alpha-methylzymosterol greater than 14alpha-methylzymosterol. Exogenous 4,4-dimethylzymosterol was not transmethylated by mutant D10. Incorporation of the 14C-labelled methyl group of S-adenosyl-L-[methyl-14C]methionine into the sterols of a D10 culture preloaded with zymosterol indicated that zymosterol was a better (40 X) substrate than endogenous lanosterolmfeeding zymosterol to D10 and a polyene-resistant strain of Saccharomyces cerevisiae (Nys-P100) that was also blocked at removal of the C-14 methyl group gave 24-methyl sterols possessing delta22 and ring B unsaturation. Mutant D10 was able to produce ergosterol from zymosterol whereas Nys-P100 produced ergosta-7,22-dienol. When grown in the presence of 3 micrometer 25-aza-24,25-dihydrozymosterol, a known inhibitor of the delta24-sterol methyltransferase, Nys-P100 accumulated 14alpha-methylzymosterol, a minor metabolite in this mutant under normal growth conditions and hitherto unidentified as a yeast sterol.