Background/Purpose:
Giant Cell Arteritis (GCA) is a granulomatous systemic vasculitis with a prediliction for the aorta and it’s extracranial branches. The majority of the morbidity associated with GCA is related to its ischaemic complications of acute visual loss and stroke. It has previously been shown that patients with cranial ischaemic complications (CICs) due to GCA have lower temporal artery IL 6 expression and circulating levels of IL 6 than patients without CICs.1
The current study aimed to extend these previous observations by:
- Comparing the spontaneous release of IL 6 from cultured temporal artery explants of patients with GCA and CICs to those without CICs.
- Investigating the association between spontaneous release of IL 6 from the explant cultures and the presence of intimal hyperplasia and luminal occlusion on histopathology.
Methods:
Patients with suspected GCA underwent a temporal artery biopsy and had serum biomarkers assayed at baseline.
TAB sections were sent for review to a histopathologist who was blinded to the clinical presentation.
Additional sections were cultured for 24 hours and IL 6 expression in the supernatants quantified by ELISA.
Temporal artery explants from 7 patients with GCA (3 TAB positive, 4 TAB negative & 1 patient with a documented CIC) were embedded in matrigel, stimulated with recombinant IL 6 at concentrations of 20 ng/ml and 40 ng/ml and myofibroblast outgrowths observed over a 3 week period.
Results:
30 patients had a temporal artery biopsy (TAB) that was positive for GCA. 25 had a negative or inconclusive TAB but met ACR classification criteria for GCA and were therefore included in the analysis.
11/55 (20%) patients presented with an ischaemic complication attributable to GCA.
Baseline demographics were similar between those with CICs and those without. Other than their presenting CICs, there was no difference in any of the other clinical manifestations of GCA between both groups.
Cumulative steroid dose pre biopsy was higher in those presenting with a cranial ischaemic complication than those without (p =0.015) However, there was no correlation observed between cumulative steroid dose and expression of IL 6 in explant cultures.
There was a trend both towards a lower baseline CRP and IL 6 in those with CICs than those without but this was not statistically significant. (Mean CRP 33 g/L vs 49 g/L and mean IL 6 17.23 pg/ml vs 31 .83 pg/ml)
Patients with CICs had significantly lower levels of of IL 6 in explant supernatants when compared to those without CICs (Mean 8.66 ng/ml/mg biopsy weight vs 18 .92 ng/ml/mg biopsy weight, p <0.01).
This lower tissue IL 6 production was significantly associated with both intimal hyperplasia (p < 0.03) and luminal occlusion (p < 0.01) on histopathology.
In addition, rIL 6 induced myofibroblast outgrowths at concentrations of 20 ng/ml but had a significant inhibitory effect at 40 ng/ml
Conclusion:
The study confirms the association between lower levels of IL 6 expression in patients with CICs than those without. The inhibitory effect on myofibroblast outgrowths at higher concentrations of IL 6 merits further investigation given the known involvement of myofibroblasts in the development of intimal hyperplasia and occlusion.
1. Cid et al. Circulation 2003
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Disclosure:
L. O’Neill,
None;
J. McCormick,
None;
D. Molloy,
None;
D. J. Veale,
None;
C. Murphy,
None;
G. M. McCarthy,
None;
U. Fearon,
None;
E. S. Molloy,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/lower-tissue-expression-of-il-6-in-patients-with-giant-cell-arteritis-presenting-with-a-cranial-ischaemic-compication/