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Abstract Number: 682

IL-12p70 Levels Play a Role in Damage Accrual in SLE Patients

Eoghan M. McCarthy1, Ruth Lee2, Joan Ni Gabhann3, Siobhan Smith3, Michele Doran4, Gaye Cunnane5, Donough G. Howard2, Paul G. O'Connell1, Caroline Jefferies3 and Grainne M. Kearns6, 1Rheumatology, Beaumont Hospital, Dublin, Ireland, 2Rheumatology, Beaumont Hospital, Dublin 9, Ireland, 3Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland, 4Rheumatology Dept, St James's Hospital, Dublin, Ireland, 5Dept of Rheumatology, St. James's Hospital, Dublin, Ireland, 6Rheumatology Department, Beaumont Hospital, Dublin, Ireland

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: cytokines and systemic lupus erythematosus (SLE)

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Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Whilst the role of cytokines in promoting disease activity in SLE is well established, the relationship between cytokines in those who sustain irreversible damage and those who remain damage free over long term follow up is less well studied. An IL-12 driven Th1 polarisation has been proposed as a promoter of irreversible renal damage in patients with lupus nephritis but studies have not extrapolated these findings to composite all organ damage scores.The primary objective of this is to explore the role of IL-12p70 in the aetiology and pathogenesis of SLE in a homogenous Irish Caucasian population.

Methods:

Patients who met at least 4 of the American College of Rheumatology (ACR) criteria for SLE were included. To gain entry all patients had to confirm they were of Irish descent for three generations. Serum levels of the following cytokines – IL-1β, IL-10, IL-12p70 and TNF-α – were quantitatively determined by electrochemiluminescence. Demographic data, disease activity as per SLEDAI and damage scores (SLICC) at 5 year follow-up were calculated.

Results:

45 patients were included in the study.

The levels of TNF-α(44.6pg/ml v 5.23pg/ml, p<.001), IL-1(2.8pg/ml v .62pg/ml, p<.001) and IL-10(7.143pg/ml v 2.76pg/ml, p<.001) were significantly higher in patients when compared to controls. IL-12p70 responses were lower in patients than controls, with an IL-12p70 level of 4.6pg/ml recorded in patients and 6.195pg/ml in controls (p=.39).

The ratio of all Th1 cytokines assayed to IL-12 was significantly higher in SLE patients when compared to controls. The levels of IL-1β/IL-12 and TNF-α/IL-12 were 5 times and 4.4 times higher respectively in patients than controls (p<.001). A similar result was seen for Th2 cytokines with the IL-10/IL-12 ratio 3.7 times higher in patients when compared to controls(p<.001).

The IL-1/IL-12 ratio was significantly higher in those patients who suffered new damage compared to those who remained damage free(1.02 v .44, p<.005) at five year follow up. A similar difference was seen in the IL-10/IL-12 ratio (3.07 v 1.88, p<.027) and the TNF/IL-12 ratio (8.14 v 5.04, p<.038).

When the Spearman correlation was computed for SLEDAI and the above cytokine ratios no significant correlation was observed with respect to disease activity. Despite this lack of association with disease activity, when a similar analysis was performed for the cytokines ratios and damage accumulation over the follow-up period a significant correlation was seen between damage accrual and the IL-1/IL-12 ratio (r = 0.431,p=0.003), IL-10/IL-12 ratio (r =0.351,p =.018) and TNF/IL-12 ratio (r = 0.28,p=.028), indicating IL-12 plays a key role in damage accrual in concert with both Th1 and Th2 cytokines.

When the respective ratios were analysed as per ACR diagnostic criteria significant differences were observed for the IL-1/IL-12 ratio(1.86 v .78,p<.0362), IL-10/IL-12 ratio(3.58 v 2.2, p<.0084) and TNF/IL-12 ratio(30.6 v 6,p<.0097) with respect to renal involvement only.

Conclusion:

Our results highlight that increased Th1 and Th2 cytokine levels relative to IL-12p70 in this homogenous Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at five year follow-up.


Disclosure:

E. M. McCarthy,
None;

R. Lee,
None;

J. Ni Gabhann,
None;

S. Smith,
None;

M. Doran,
None;

G. Cunnane,
None;

D. G. Howard,
None;

P. G. O’Connell,
None;

C. Jefferies,
None;

G. M. Kearns,
None.

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