Background/Purpose: Multiple cytokines play a role in the immune dysregulation seen in systemic lupus erythematosus (SLE) and the local inflammatory responses that ultimately lead to tissue injury. IL6, TNFα, sCD40L, IFNα and IFN inducible cytokines such as MCP1 and IP10 are correlated with disease activity as measured by the SLEDAI, SLAM-R, ESR and anti-dsDNA antibody titres. Elevated VEGF and IL1β levels have been demonstrated in patients with antiphospholipid syndrome (APS). Low serum 25-hydroxy vitamin D (25OH-VD) levels are found in sera of pts with SLE and have been associated with higher fatigue and pain scores.  Studies assessing lupus disease activity and Vit D levels have shown contradictory results. As such we sought to determine the proinflammatory biomarkers elevated in a cohort of SLE patients compared to controls, the correlation with disease activity levels and the prevalence of abnormally low vitamin D levels.

Methods: 388 patients with samples from baseline visit were selected from a longitudinal cohort of SLE subjects. IFNα2, IL1β, IL6, IL8, IP10, TNFα, VEGF and sCD40L levels were determined by a multiplexed immunoassay [Millipore]. Disease activity was assessed using SELENA-SLEDAI scores. 25OH-VD levels were measured using either a chemiluminescence or ELISA assay, and pts classified into 3 groups: normal (25OH-VD >30 ng/mL), insufficient (20-30) and deficient (<20). The non-parametric two-sample median test was used to compare medians of cytokines in SLE pts vs controls. Pearson correlation was used to identify association of disease activity and physician global assessment (PGA) with cytokine levels.

Results: Most cytokines were significantly elevated in SLE patients vs controls, with the exception of IL8 that was significantly elevated in controls (Table). Of 379 subjects with 25OH-VD results, 36.1% (137/379) had deficiency, 29.3% (111/379) had insufficiency and 34.6% (131/379) had normal 25OH-VD levels. IP10 correlated with PGA and SLEDAI (PGA:0.15, p=0.0034 and SLEDAI:0.26, p<0.0001). All other correlations of cytokines and 25OH-VD with PGA and SLEDAI were not significant.

Table 1. Levels of cytokines in SLE patients vs control group

Cytokines	Controls/Median (N=30)	SLE/Median (N=388)	P-value
INFα2	0	10.37	0.012
IL-6	0	0.63	0.0025
IL-8	27.40	7.07	<0.0001
IL-1β	0	0.02	0.0004
TNFα	0	7.52	<0.0001
VEGF	88.30	158.65	0.0025
IP-10	96.22	413.48	<0.0001
sCD40L	16.39	2163.51	<0.0001

Conclusion: This study confirms numerous reports of elevated proinflammatory cytokines in SLE patients. Interestingly, over 2/3 of this population of SLE patients had below normal vitamin D levels but no correlation with SLEDAI or PGA was seen. The IFN-inducible cytokine IP10 correlated with increased disease activity as determined by both objective and subjective measures.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-pro-inflammatory-cytokines-and-vitamin-d-levels-in-a-lupus-cohort-and-correlation-with-disease-activity/