O. S. Zhukov

Introduction The time‐dependent nature of factor VIII (FVIII) inhibitors is well described, and the standard FVIII Bethesda assay used to measure inhibitors incorporates a 2‐hour incubation. Despite case reports and reviews describing the immediate‐acting nature of factor IX (FIX) inhibitors, many coagulation laboratories continue to use a traditional prolonged incubation for FIX Bethesda assays. To our knowledge, a comprehensive evaluation of the FIX Bethesda assay without incubation has not been reported. Aim The goal of this study was to evaluate the performance of a rapid FIX Bethesda (ie no incubation) compared with the standard Bethesda assay (2‐hour incubation). Methods The analysis used a Bethesda assay configured for either immediate testing or a 2‐hour incubation. Samples from 14 haemophilia B patients with inhibitors and 9 non‐human controls were tested. Results The two assays yielded similar performance overall. The average per cent difference in inhibitor titre between the rapid and standard FIX Bethesda assay was −3% (range −15% to +13%; P = .175) for patient samples and −2% (range −17% to +14%; P = .376) for controls. Conclusion The rapid Bethesda assay showed good agreement with the standard Bethesda assay for determination of inhibitor levels in patients with severe haemophilia B. The rapid assay allows for faster assessment of inhibitors in patients with severe haemophilia B and has the potential to improve the ability of the coagulation laboratory to perform testing from a logistical viewpoint. Further studies involving larger numbers of patients would be important to confirm our findings.

Background The 14-3-3 proteins are ubiquitously-expressed intracellular chaperonins. Expression of the η (eta) isoform is restricted to synovial and CNS tissues.¹ Extracellular 14-3-3η induces proinflammatory MAPK and NFkB cascades in THP-1 cells in vitro.² Extracellular 14-3-3η has been proposed as a novel biomarker for joint damage in rheumatoid arthritis (RA) and psoriatic arthritis, with serum elevation occurring in early RA. 14-3-3η positivity may add diagnostic sensitivity to laboratory RA markers such as rheumatoid factor (RF) and citrullinated cyclic peptide antibody (CCP).³ However, 14-3-3η expression in arthritogenic viral infection has not been studied. Objectives The aim of this study was to determine the frequency of elevated 14-3-3η in patients with RA and in those with HCV, acute EBV, or acute B19 infections. Methods We have developed a quantitative 14-3-3η sandwich ELISA and verified the reference range using 134 serum specimens from healthy donors (67 males, 67 females; ages 18-65). 14-3-3η was measured in de-identified residual clinical specimens originally submitted for routine RA or infectious disease diagnostic testing. Results The 14-3-3η 95th-percentile reference range was defined as Conclusions 14-3-3η elevation was most frequent among patients with RF+/CCP+ results (consistent with an RA diagnosis). 14-3-3η elevation also occurred less frequently in the RF+/CCP-, RF-/CCP-, HCV, EBV, and B19 groups. The data suggest that RA and some HCV, EBV, and parvovirus B19 infections may share pathogenetic mechanisms characterized by synovial release of 14-3-3η. Of note, the median abnormal 14-3-3η level was higher in the RF+/CCP+ group than in the virus-infected groups, suggesting less synovitis in viral arthritis than in RA, which is consistent with clinical observations. References Kilani et al. J Rheum 34:1650-7, 2007. Marotta A. Arth Rheum 63 suppl 10: 1836, 2011 Maksymowych et al. Arth Rheum 64 suppl 10:977, 2012. Disclosure of Interest O. Zhukov Employee of: Quest Diagnostics Nichols Institute, R. Abolhosn Employee of: Quest Diagnostics Nichols Institute, J. Popov Employee of: Quest Diagnostics Nichols Institute, S. Naides: None Declared