Background/Purpose:

Systemic lupus erythematosus(SLE) is a systemic autoimmune disease characterised by the deregulated activation of T and B lymphocytes, production of autoantibodies and the formation of immune complexes causing tissue damage. Chemokines which are normally involved in leucocyte chemotaxis have been associated with tissue injury in SLE via leucocyte infiltration. We sought to assess the relationship between serum levels of a number of chemokines and disease activity, damage scores and clinical profiles in Caucasian SLE patients.

Methods: Serum levels of the following chemokines were determined by ELISA – CXCL10, CXCL13, CCL17 and CXCL8. Demographic data, disease activity as per SLEDAI and damage scores (SLICC) at baseline and 5 year follow-up were recorded. Active disease was defined as a SLEDAI score > 6. Categorical variables were analyzed using Fisher’s exact test and continuous variables by unpaired t-tests. The Mann-Whitney test was used in instances of non-normality.

Results:

45 patients were recruited. Serum levels of CXCL10, CXCL13, CCL17 and CXCL8 were higher in SLE patients than controls (Table1).

	Patient(pg/ml)IQR range	Control(pg/ml)IQR range	P-Value
CXCL10	234.6 [85.49;499]	84.76 [46.59;107.3]	0.001
CXCL13	311.6 [131.4;545.8]	64.99 [43.49;444.4]	0.01
CCL17	117.2 [69.21;181.3]	32.93 [18.49;171.2]	0.0097
CXCL8	6.13 [4.52;10.43]	1.7 [1.27;1.985]	0.0001

Significantly higher levels of CXCL10 were observed earlier in disease course as well as in those patients with active disease (493.5pg/ml v 94.2 pg/ml, p=0.0045) and those who suffered damage over the 5 year follow up period (407.1pg/ml v 94.2pg/ml, p=0.006). CCL17 and CXCL8 were also higher in patients with active disease [CCL17 (211.7pg/ml v 108.2pg/ml, p <0.0001), CXCL8 (9.784pg/ml v 5.576pg/ml, p=0.0199)]. CXCL13 levels failed to show an association with disease activity.

Regarding clinical involvement CXCL10 levels were higher in those with CNS involvement (649.7pg/ml v 151.7pg/ml, p = 0.02) whilst higher levels of CCL17 were observed in those with both renal involvement (146.8pg/ml v 113.4pg/ml, p = 0.046) and serositis (166.8pg/ml v 108.8pg/ml, p = 0.039) as part of their ACR diagnostic criteria. Of note CXCL10 and CXCL8 levels were also elevated in those with immunological involvement.

When each of the chemokines was analysed with respect to antibody profile higher levels of CXCL8 were seen in patients who were La +ve versus La -ve (11.16pg/ml v 5.9pg/ml, p = 0.04). None of the other chemokines assayed demonstrating an association with an antibody signature.

Finally a strong correlation was seen between CXCL10 and CXCL13 levels in SLE patients (Spearman r = 0.711, p < 0.001) indicating the importance of the interferon pathway to their induction. Both CXCL8 and CCL17 levels failed to show a correlation with any of the other chemokines measured suggesting that these chemokines are driven by distinct mechanistic pathways in SLE.

Conclusion:

Chemokines play an important role in the pathogenesis of SLE with CXCL10, CXCL8 and CCL17 levels all reflecting disease activity. In addition CXCL10 levels are higher in CNS involvement whilst we have demonstrated enhanced CCL17 levels in those with patients renal involvement.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/chemokine-expression-in-systemic-lupus-erythematosus/