Background/Purpose: Accelerated atherosclerosis is the major cause of late mortality in SLE.  Interferon alpha plays a role in atherosclerosis by deleting endothelial progenitor cells and causing endothelial dysfunction.  NZM and Apo E -/- mice exposed to IFN-alpha develop platelet activation and thrombosis.  Loss of Type I interferon receptor signaling improves endothelium dependent vasorelaxation, endogenous progenitor cell numbers and function and neoangiogenesis.  We investigated whether the interferon alpha gene signature would predict changes in subclinical measures of atherosclerosis in human SLE over 2 years.

Methods: 70 SLE patients, 91% female, 60% Caucasian, 34% African-American, 6% others, mean age  43±10 yrs had coronary artery calcium (CAC) measured by helical CT and carotid intima-media thickness by carotid duplex.  The IFN gene signature was determined in peripheral blood RNA using Affymetrix chips.

Results: At baseline, there was no difference in coronary calcium or IMT progression with low vs. high interferon gene signature.  Patients with high interferon signature had lower CAC scores at baseline and 2 years but the difference between the 2 groups was not statistically different.

Table 1. Changes in coronary artery calcium (CAC) and carotid intima-media thickness (IMT)

Measure	Mean at baseline	Mean after 2 years	Mean Change	p-value for baseline between groups*	p-value for change within group	p-value for change between groups*
Loge(CAC score+1)
Low IFN	1.48	1.69	0.21	0.38	0.22	0.24
High IFN	0.90	0.81	-0.09		0.68
Carotid IMT
Low IFN	0.58	0.67	0.10	0.52	0.0008	0.54
High IFN	0.56	0.63	0.07		<0.0001

* P-value when age, gender, and ethnicity are controlled

 Conclusion: In contrast to in vitro and murine studies which clearly show a role of interferon alpha in atherosclerosis, our study failed to find any difference in coronary calcium progression or carotid IMT progression over 2 years, comparing low vs. high signature patients.  In fact, the high interferon gene signature group had no progression in coronary calcium over 2 years.  Although interferon could still be acting locally at the level of the coronary artery, our study suggests that we must look elsewhere to identify a genetic biomarker of atherosclerosis in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-interferon-alpha-gene-signature-is-not-associated-with-nor-does-it-predict-progression-of-coronary-artery-calcium-cac-or-carotid-intima-media-thickness-imt-in-systemic-lupus-erythematosus-sle/