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In order to analyse telomere length in subsets of human peripheral blood lymphocytes and monocytes, we modified a recently developed multicolor flow-fluorescent in situ hybridization (FISH) methodology that combines flow-FISH and antibody staining for cell surface antigens. We analysed telomere length of peripheral blood mononuclear cells in a group of 22 patients with systemic lupus erythematosus (SLE) and 20 age-matched healthy donors. We found that neither CD4ϩ, CD8ϩ, CD19ϩ cells nor CD14ϩ monocytes have significantly shorter telomeres compared with their healthy counterparts. On the basis of these findings, we then used monocyte telomere length as internal reference in order to control for intra-individual variability in telomere length. By using this approach, we could demonstrate significant telomere shortening in all three lymphocyte subsets (in all cases P Ͻ 0.05) compared with monocytes. However, these differences did not vary significantly between SLE patients and controls. In summary, telomere lengths in subpopulations of hematopoietic cells can be monitored in patients with SLE using multicolor flow-FISH. While confirming data by other groups on telomere length in lymphocyte subpopulations, our data argue against an increased proliferation rate of peripheral blood monocytes reflected by accelerated telomere shortening in patients with SLE. Lupus (2007) 16, 955-962.Key words: flow-FISH; monocyte; systemic lupus erythematosus; telomere; telomerase Lupus (2007) 16, [955][956][957][958][959][960][961][962]

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ObjectiveTo assess whether tocilizumab treatment is associated with changes in depression symptoms in patients with rheumatoid arthritis (RA) during routine daily care. MethodsWe retrospectively analysed data from a German non-interventional study (ARATA) of adult, tocilizumab-naïve RA patients who initiated subcutaneous tocilizumab and were followed for 52 weeks. The Beck Depression Inventory II (BDI-II) was used to assess symptoms of depression and create baseline subgroups of no (BDI-II<14), mild (14-19), moderate (20-28), and severe (≥29) depression. Other key outcomes included Disease Activity Score-28 joints (DAS28), patient-reported outcomes (PROs), and adverse events. Mixed model repeated measures (MMRM) assessed the impact of DAS28 on BDI-II over time, and Pearson correlation analyses evaluated associations between changes from baseline. ResultsOf 474/1155 ARATA patients who completed the BDI-II at baseline, 47.7% had evidence of depression: 18.4% mild, 17.7% moderate, and 11.6% severe. 229 patients (48.3%) completed the BDI-II at both baseline and week 52. Two-thirds of patients with moderate or severe depression at baseline improved to a milder or no depression subgroup at week 52 (44/65 [67.7%]). Improvements in disease activity and PROs were observed in all subgroups, but patients with depression had lower response and higher adverse events rates. We observed an association between DAS28 and BDI-II over time in MMRM analyses, but the Pearson correlation for change from baseline was weak (r=0.10). Conclusion Depression is common in patients receiving routine care for RA. Improvements in depressive symptoms in RA duringtocilizumab therapy appear to be distinct from changes in disease activity.

Background Interpretation of medical images needs to be standardized and trained. This applies also to fluorescence-optical imaging (FOI), a novel tool for assessment of inflammation in patients with arthritis (1). In this study we refined and evaluated the inter-reader reliability of the previously described algorithm of image interpretation of FOI. Objectives To determine the inter-reader reliability of the fluorescence optical imaging activity score (FOIAS) 7 readers from 4 centres each evaluated 34 randomly selected cases (5 RA, 5 PsA, 5 remissions, and 19 EA). FOIAS was analyzed in PrimaVistaMode (PVM) and 3 phases (P1, P2, P3). All participants were blinded for diagnosis and clinical findings. Overall, 28560 data sets were evaluated. Methods All participants were initially trained in software use and basic image interpretation by the supplier of the system. 5 of the 7 readers had no knowledge in the standardized image evaluation. Before starting the study a 2.5h training session was carried out and repeated once. All participants obtained a guideline and picture samples. For image interpretation, the automatically generated gain had to be checked by the readers and corrected as appropriate. The readers had to determine the 3 phases, and evaluate all 4 datasets of each case according to the guideline. Spearman correlations, agreement rates (2) and Cohen’s kappa coefficients were calculated. Results Correlations and agreement rates are presented in table 1. Two readers (2,4) showed relevant difference to the other readers. Cohen’s Kappa was between moderate and substantial. Highest Kappa was found for PVM (κ=0.68). FOIASSpearman correlations,Spearman correlationsAgreement rates,Agreement rates All readerswithout 2 and 4All readerswithout 2 and 4 PVM0.5 ≤r≤0.90.7 ≤r≤0.969%≤AR≤91%82%≤AR≤91% P10.4 ≤r≤0.80.5 ≤r≤0.885%≤AR≤94%88%≤AR≤94% P20.5 ≤r≤0.90.6 ≤r≤0.953%≤AR≤83%72%≤AR≤83% P30.5 ≤r≤0.80.5 ≤r≤0.879%≤AR≤95%87%≤AR≤93% Conclusions There was overall a good to nearly perfect correlation between readers. Thus standardized FOI evaluation gives high agreement in assessment of disease activity using FOIAS. There was high agreement for the decision if a joint is affected or not. Cohens Kappa showed that the standardized protocol is reliable after training. Highest Kappa was found for PVM. This is explicable with the fact, that PVM is a static image, while the image stack is dynamic. Reader 2 and 4 had problems in image interpretation depending on a dyschromatopsia and wrong image adjusting. Further training will be helpful. In conclusion, the used standardized protocol for assessment of inflammatory activity in FOI seems to be reliable and useful in daily practice. Redetermination of interreader-reliability after further refining of the protocol and training is planned. References Werner SG, Langer HE, Ohrndorf et al. Inflammation assessment in patients with arthritis using novel in vivo fluorescence optical imaging technology. Ann Rheum Dis 2011, Epub ahead of print. Schwenke C and Busse R. Analysis of differen...