FRI0017 Ox40 and ox40l are highly associated with autoantibody formation in early rheumatoid arthritis, and predict flare after anti-tnf discontinuation.
Authors: J. K. Laustsen, T. Kruse Rasmussen, K. Steengaard-Pedersen, M. L. Hetland, K. Hørslev-Petersen, M. Hvid, B. W. Deleuran
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune disease characterised by the presence of autoantibodies and autoreactive T cells, leading to synovitis and progressive destruction of the joints. The TNF-family members OX40 and OX40L are crucial for the generation of memory T cells, which can lead to persistence of immunity, if the T cells are autoreactive (1), Both molecules exist in a soluble form (s), and have previously been connected to autoimmune diseases (2). Furthermore, sOX40 have been suggested to be antagonistic to the membrane bound form, and thereby have an anti-inflammatory function (3). <h3>Objectives</h3> To investigate the presence and bioactivity of sOX40 and sOX40L and their association with disease activity and progression in RA <h3>Methods</h3> Plasma samples from early RA patients (eRA, n=76) randomised to conventional DMARD treatment with or without 12 months of adalimumab treatment were obtained from the OPERA study. Correlations between plasma levels of sOX40 and sOX40L (analysed by ELISA; detection limits 5.97 pg/ml and 1.16 ng/ml, respectively) at 0, 3, and 12 months after treatment initiation and DAS28, HAQ, IgM-RF, and anti-CCP were calculated. The results were compared with a transverse sample set of chronic RA patients (cRA, n=12, disease duration &gt; 8 years) and with healthy volunteers (HV, n=32). All data are expressed as median. <h3>Results</h3> eRA had a low amount of sOX40 at baseline (5.97 pg/ml), which increased to 11.47 pg/ml at 12 months (p&lt;0.0001). The level at 12 months was also significantly increased compared with both HV and cRA (all p&lt;0.005). Soluble OX40L was significantly elevated (18.30 ng/ml) compared with HV (1.16 ng/ml, p&lt;0.0001) and cRA (1.59 ng/ml, p&lt;0.01), and remained elevated at 12 months (15.10 ng/ml, p=0.7). Soluble OX40 and sOX40L levels were unaffected by addition of adalimumab treatment. The levels of sOX40L were strongly associated with presence of IgM-RF and anti-CCP at 0 months (rho=0.5 and 0.4, respectively, p&lt;0.0001). The sOX40/sOX40L ratio was significantly decreased in eRA compared with HV and cRA (all p&lt;0.0001). The sOX40/sOX40L ratio at adalimumab discontinuation (12 months) correlated with disease flare in the following 6 months (p=0.007) <h3>Conclusions</h3> The findings of this study showed, that sOX40L was markedly elevated in eRA compared with HV and cRA, suggesting that sOX40L plays a key role in early RA. The level of sOX40L remained high despite adalimumab treatment, and sOX40 levels increased, indicating that anti-TNFα treatment does not affect memory generation. Combined with the predictive values of the sOX40L/sOX40 ratio to risk of disease flare this dysfunction in the OX40 system could explain why many patients experience relapse after anti-TNF discontinuation <h3>References</h3> : Ishii et al., <i>OX40-OX40L interaction in T-cell mediated immunity and immunopathology</i>, Advances in immunology, chapter 3, 2010 M. Croft, <i>Control of immunity by the TNFR-Related molecule OX40 (CD134</i>), Annu. Rev. Immunol 2010, 28. 57-78 R Sibliano et al., <i>Technical advance: soluble OX40 molecule mimics regulatory T cell modulatory activity on FCεRI-dependent mast cell degranulation</i>, J Leukoc Biol. 2011 <h3>Disclosure of Interest</h3> None Declared