Format

Send to

Choose Destination
J Autoimmun. 2019 Jul 15:102302. doi: 10.1016/j.jaut.2019.07.001. [Epub ahead of print]

The association of serum interleukin-6 levels with clinical outcomes in antineutrophil cytoplasmic antibody-associated vasculitis.

Author information

1
Mayo Clinic, Rochester, MN, USA.
2
University of Michigan Medical School, Ann Arbor, MI, USA.
3
Cleveland Clinic, Cleveland, OH, USA.
4
University Medical Center Groningen, Groningen, Netherlands.
5
Johns Hopkins University, Baltimore, MD, USA.
6
Hospital for Special Surgery, New York, NY, USA.
7
Duke University Medical Center, Durham, NC, USA.
8
Massachusetts General Hospital, Boston, MA, USA.
9
Boston University and VA Boston Healthcare System, Boston, MA, USA.
10
Mayo Clinic, Rochester, MN, USA. Electronic address: specks.ulrich@mayo.edu.
11
University of Pennsylvania, Philadelphia, PA, USA.

Abstract

OBJECTIVE:

To investigate serum IL-6 (sIL-6) levels during active disease, complete remission (CR), and relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to explore the association of changes in sIL-6 with clinical outcomes.

METHODS:

sIL-6 levels were measured at baseline and longitudinally over 18 months, in 78 patients with AAV enrolled in a randomized controlled trial comparing treatment with either rituximab (RTX) or cyclophosphamide (CYC)/azathioprine (AZA). Outcome variables included baseline clinical features, ANCA specificity, disease activity (active disease versus CR), time to relapse events, B cell repopulation, and ANCA titer increases.

RESULTS:

At baseline, sIL6 levels were detectable in 81% of patients; 73% (n = 57) of subjects were proteinase 3 (PR3)-ANCA positive, sIL-6 levels were higher in subjects with PR3-ANCAs and positively correlated with their levels (rs = 0.36,p < 0.01), but not with levels of myeloperoxidase (MPO)-ANCA (rs = -0.17,p = 0.47). Higher baseline sIL-6 levels were associated with PR3-ANCA positivity, fever, pulmonary nodules/cavities, conductive deafness, and absence of urinary red blood cell casts (p < 0.05). Baseline sIL6 levels did not predict CR at month 6 (p = 0.71), and the median sIL-6 level declined from baseline with induction therapy, regardless of CR achievement. An increase in sIL-6 during CR was a predictor for subsequent severe relapse in RTX-treated patients (hazard ratio (HR):7.24,p = 0.01), but not in CYC/AZA-treated patients (HR:0.62,p = 0.50). In contrast, a sIL-6 increase did not predict B cell repopulation or ANCA titer increase in either treatment arm (p > 0.05).

CONCLUSION:

At baseline, sIL-6 concentrations correlate with PR3-ANCA titers and are associated with specific clinical manifestations of AAV. Baseline sIL6 concentrations do not predict CR at 6 months, but the increase in sIL-6 concentrations during CR is associated with subsequent severe relapse among RTX-treated patients. Further investigation into the mechanistic role of IL6 in AAV might lead to identifying this pathway as a potential therapeutic target in this disease.

KEYWORDS:

ANCA-Associated vasculitis; ANCA-type; Cytokines; IL-6; Interleukin-6; RAVE

PMID:
31320177
DOI:
10.1016/j.jaut.2019.07.001

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center