Article Text

PDF
OP0190 Increased Serum Levels of IFN-Λ Correlate with Th17 Axis Cytokines and Independently To IFN-α Identify Patient Group with Higher Organ Damage
  1. V. Oke1,
  2. S. Brauner1,
  3. A. Larsson2,
  4. J. Gustafsson1,
  5. A. Zickert1,
  6. I. Gunnarsson1,
  7. E. Svenungsson1
  1. 1Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm
  2. 2Department of clinical Chemistry and Pharmacology, Uppsala University, Uppsala, Sweden

Abstract

Background Type I interferons (IFN), particularly IFN-αs, are considered to have a pivotal role in SLE. Recently, increased levels of type III IFNs (IFN-λs) have been described to be also associated with SLE.

Objectives We measured circulating levels of IFN-λ, IL-17, IL-23, IP-10 and also IFN-α, in a cohort of SLE patients and investigated their association with clinical and laboratory manifestations of the disease. 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 examined by clinician rheumatologist and assessed for current organ manifestations and disease related organ damage. Sera were collected at inclusion and stored at -70* C until analysis. Serum levels of IFN-α, IFN- λ, IL-17, IL-23 and IP-10 were measured in sera by commercial ELISA.

Results IFN-λ was detected in 76 (29,1%) patients and IFN-α in 115 (44%). In 108 patients (41.4%) neither of the cytokines was detected. Both IFN-λ and IFN-α were detected more often and in higher levels in patients. IFN-λ levels did not correlate to the levels of IFN-α, and only in 38 (14.5%) patients had detectable levels of both. Levels of IL-17, IL-23 and IP-10 correlated with each other and with IFN-λ. In comparison, only a weak correlation between levels of IFN-α and IL-23 was observed. Detectable levels of IFN-λ were associated with lower incidence of fever, photosensitivity and also arthritis. Patients with detectable IFN-α had active mucocutaneous disease, serositis and lower levels of C3 and C4, and also presence of anti-Ro/SSA and anti-La/SSB. Incidence of nefritis and DVT was lower in this group. Co-detection of IFN-α and IFN-λ was significantly associated with lymphadenopathy, serositis, cortical dysfunction and presence of antiphospolipid antibodies. IFN-α was associated with overall lower disease damage. However, IFN-λ was associated with lower incidence of musculoskeletal, but higher frequency of cerebrovascular damage. The triple detection of IFN-λ, IL-17 and IL-23 was significantly associated with overall higher disease damage score, and particularly higher incidence of renal damage.

Conclusions Our study demonstrates that in SLE patients the levels of IFN-α and IFN-λ do not correlate, but rather dissect patient's groups with different target organs. Triple positivity for IFN-λ, IL-17 and IL-23 is associated with the higher disease damage, in particular kidney damage.

  1. Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity. Wu Q, Yang Q, Lourenco E, Sun H, Zhang Y. Arthritis Res Ther. 2011 Jun 16.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.