THU0034 High Serum Levels of IFN-Lambda1/3 and IFN-Alpha Characterize Two Separate Sub-Groups among SLE Patients
Authors: V. Oke
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> SLE is a systemic autoimmune disease with heterogeneous clinical manifestations and still not completely dissected pathogenesis. Both the innate and the adaptive immune systems are dysregulated. IFN-α is known as an important cytokine driving disease manifestations in a subgroup of patients, and type III IFNs (IFN-λ1, -2 and -3) have recently been described to be associated with renal involvement (1). <h3>Objectives</h3> We studied circulating levels of IFN-α and IFN-λ1/3 and their association with clinical and laboratory manifestations in a large cohort of SLE patients. Population controls were investigated as comparators. <h3>Methods</h3> 261 SLE patients and 276 population controls, identified through the population registry and matched for age, sex, and region of living, were included. All participants were investigated clinically by a rheumatologist regarding present and previous organ manifestations. Sera were collected after over-night fasting at inclusion and stored at -70°C until analysis. IFN-α and IFN-λ1/3, levels were measured in sera by commercial ELISA (pan IFN-α and IFN-λ1/3, lowest detection limit 0.022 pg/l and 0.3 pg/l respectively). <h3>Results</h3> IFN-α was detected in 154 (59%) patients and IFN- λ1/3 in 76 (29,1%) and 79 patients (30%) hade no detectable levels of any of those. In comparison to controls, patients had higher levels of both IFN-α and IFN- λ1/3 p&lt;0.01. IFN-λ1/3 levels did not correlated to the levels of IFN-α (figure). Two patient groups were identified, one with high (&gt;1.3 pg/l) levels of IFN-λ1/3 (n=37) and the other with high (&gt;0.112pg/l) IFN-a levels (n=39) (see figure). There were only 5 patients (cross symbol in the figure) who had high levels of both cytokines. For further statistical analysis patients were grouped accordingly to the figure. Patients with high IFN-λ1/3 levels were compared to the patients with high IFN-α and to the rest of the patients. Statistical analysis included occurrence of common clinical SLE manifestations and autoantibodies. Both IFN-α and IFN- λ1/3 high groups had leukopenia (likelihood ratio (LR), p&lt;0.05) and thrombocytopenia (LR, p&lt;0.01) at a higher proportion in comparison to the rest of the patients, but they did not differ regarding occurrence of malar rash, photosensitivity, discoid LE, arthritis, nephritis. Patients with high IFN-α were more often positive for SSA, SSB (LR, p&lt;0.01) and anti-C1q autoantibodies (LR, p&lt;0.05) and had a tendency for less frequent occurrence of any antiphospholipid antibodies (LR, p=0.06). Both the IFN-λ1/3 and IFN-α high groups had lower C3 levels as compared to the other patients (LR, p&lt;0.05 and 0.005, respectively). There were less smokers among patients having high IFN-λ1/3 levels in comparison to IFN-α high and to the rest of the patients (LR, p&lt;0.01). Notably, 3 patients with active carditis and 4 with organic brain syndrome, as assessed by SLAM/SLEDAI, were in the high IFN-α group (LR, p&lt;0.05). <h3>Conclusions</h3> Our study demonstrates that among SLE patients high levels of IFN-α and high levels of IFN-λ1/3 reside in two different subgroups with minimal overlap. Both cytokines may independently drive SLE disease manifestations, and could be considered for future drug development. <h3>References</h3> Wu Q et al. Arthritis Res Ther. 2011 Jun 16;13(3):R88. doi: 10.1186/ar3363. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5823