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THU0034 High Serum Levels of IFN-Lambda1/3 and IFN-Alpha Characterize Two Separate Sub-Groups among SLE Patients
  1. V. Oke
  2. on behalf of Johanna Gustafsson, Agneta Zickert, Iva Gunnarsson, Elisabet Svenungsson
  1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract

Background 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).

Objectives 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.

Methods 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).

Results 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<0.01. IFN-λ1/3 levels did not correlated to the levels of IFN-α (figure). Two patient groups were identified, one with high (>1.3 pg/l) levels of IFN-λ1/3 (n=37) and the other with high (>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<0.05) and thrombocytopenia (LR, p<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<0.01) and anti-C1q autoantibodies (LR, p<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<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<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<0.05).

Conclusions 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.

References

  1. Wu Q et al. Arthritis Res Ther. 2011 Jun 16;13(3):R88. doi: 10.1186/ar3363.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.5823

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