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THU0295 Interleukin-6 and Soluble Interleukin-6 Receptor in Large-Vessel Vasculitides
  1. L. Pulsatelli1,
  2. P. Dolzani1,
  3. E. Assirelli1,1,
  4. R. Meliconi2,3,
  5. N. Pipitone4,
  6. F. Muratore4,
  7. G. Pazzola4,
  8. L. Boiardi4,
  9. C. Salvarani4
  1. 1Laboratory of Immunorheumatology and Tissue Regeneration
  2. 2Medicine and Rheumatology Unit, Rizzoli Orthopaedic Institute
  3. 3University of Bologna, Bologna
  4. 4Division Of Rheumatology, Arcispedale S.Maria Nuova, Reggio Emilia, Italy

Abstract

Background A role for interleukin-6 (IL-6) in the pathogenesis of large-vessel vasculitides (LVV) has been suggested by previously reported results indicating increased serum IL-6 levels in patients compared to healthy controls (1,2). In addition, IL-6 relevance in LVV is also supported by genetic evidence, as highlighted by a very recent study reporting an association of specific IL-6 gene polymorphism with Takayasu's arteritis (TA) susceptibility (3). IL-6 mediates its functions through two membrane proteins: the IL-6 receptor (IL-6R) and gp130, the signal transducing element. Soluble form of IL-6R (sIL-6R), after binding with IL-6, is able to associate to membrane gp130 and mediate intracellular signalling in IL-6R negative cells. The biological activity of IL-6 strictly depends on the interrelationship occurring among these molecules and the role of sIL-6R as an inflammatory biomarker has been recognized in several diseases.

Objectives Since, to date, reliable biomarkers for assessing clinical activity in LVV are lacking, we aimed to investigate serum levels of IL- 6 and IL-6R in patients with Giant Cell Arteritis (GCA) and TA, in order to evaluate their relationship with disease activity assessed by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) and by clinical indices including National Institutes of Health-NIH/Kerr criteria and Indian Takayasu Activity Score (ITAS).

Methods Sera were obtained from 72 patients with LVV (33 GCA and 39 TA) who underwent a PET/CT scan and from 60 age-matched normal controls (NC). PET/CT scans were reviewed by a nuclear medicine physician who had no knowledge of the clinical information. Vascular uptake was graded using a 4 point semiquantitative scale. ITAS, Kerr/NIH scores and sera for serum biomarker investigations were obtained within 20 days of the PET/CT scans.IL-6 and sIL-6R serum levels were evaluated using commercial DuoSet ELISA kits (R&D Systems) following the manufacturer's instruction.

Results IL-6 and sIL-6R serum levels were significantly higher in both GCA and TA patients compared to NC (IL-6: GCA vs NC p<0.005, TA vs NC p<0.0001; sIL-6R: GCA vs NC: p<0.0005, TA vs NC: p<0.01). No significant difference was found between serum levels of GCA patients compared to TA patients. When stratifying LVV patients according to PET/CT assessment, no difference was seen between IL-6 and IL-6R levels in patients with an active scan compared to those with an inactive scan in both LVVs. Similarly, according to both ITAS and NIH/Kerr scores, no difference was found between the soluble factor levels in patients with active disease compared to inactive patients.

Conclusions IL-6 and sIL-6R were elevated in large-vessel vasculitis (TA and GCA) compared to NC, but neither soluble factor appeared to be associated with disease activity assessed both by PET/CT scan and clinical scores (Kerr-NIH and ITAS scores).

References

  1. Park MC et al., Rheumatology 2006. 2. Alibaz-Oner F et al., Clinical and Experimental Rheumatology, in press. 3. Renauer P et al, Arthritis Rheumatol 2015

Disclosure of Interest None declared

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