ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 3240

Interferon Kappa Is a Novel Type I IFN That Drives Cutaneous Inflammation in Systemic Lupus

Jasmine Stannard1, Tamra J. Reed2, Emily Myers3, Lori Lowe4, Mrinal Sarkar4, Xianying Xing5, Celine C. Berthier6, Johann Gudjonsson4 and J. Michelle Kahlenberg7, 1Int. Medicine/Rheumatology, University of Michigan, Ann Arbor, MI, 2Internal Medicine, Rheumatology, University of Michigan, Ann Arbor, MI, 3Internal Medicine, Rheumatology, Georgetown University, Washington, DC, 4Dermatology, University of Michigan, Ann Arbor, MI, 5Dermatology, University of Michigan, University of Michigan, Ann Arbor, MI, 6Nephrology, Division of Nephrology, University of Michigan Medical Center, Ann Arbor, MI, 7Internal Medicine, Division of Rheumatology, Division of Rheumatology, University of Michigan Medical Center, Ann Arbor, MI

Meeting: ACR/ARHP Annual Meeting 2016

Date of first publication: September 28, 2016

Keywords: , ,

Session Information

Date: Wednesday, November 16, 2016

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis II

Session Type: ACR Concurrent Abstract Session

Session Time: 11:00AM-12:30PM

Background/Purpose: Cutaneous lupus erythematosus (CLE) lesions are disfiguring, scarring, difficult to treat, and affect up to 70% of patients with systemic lupus erythematosus (SLE). Type I interferons (IFN) are important in the pathogenesis of SLE and CLE, yet we have insufficient data on the source of type I IFNs in the skin and the effects of type I IFNs on cutaneous inflammatory predisposition. In this work, we investigate a novel keratinocyte-produced type I IFN, IFNκ, in promotion of epidermal inflammation and CLE.

Methods:  SLE patients for study had biopsy-proven history of CLE and met 4/11 ACR criteria for SLE. Primary keratinocytes were isolated and cultured from the upper thigh of control or SLE patients. SLE keratinocytes were taken from unaffected skin. Keratinocytes from control and SLE patients were cultured and IL-6 production was measured after stimulation with toll-like receptor (TLR) ligands and ultraviolet light (UV). Neutralizing antibodies to the type I interferon (IFN) receptor and IFN kappa were used to define the role of type I IFNs on IL-6 production. IFN kappa production was measured via ELISA. Type I IFN expression in 80 CLE lesions was determined via microarray. IFNκ expression in CLE lesions was confirmed via immunohistochemistry.

Results:  Keratinocytes from unaffected skin of lupus patients produced significantly more IL-6 compared with healthy controls following exposure to TLR2 agonist or UVB radiation. This increased IL-6 production was duplicated in control keratinocytes after pretreatment with type I IFN. Importantly, secretion of keratinocyte-specific IFNκ was significantly increased after TLR2 and UVB treatment in lupus vs. control keratinocytes and neutralization of the type I IFN receptor or IFNκ was sufficient to abrogate the enhanced IL-6 production by lupus keratinocytes. In vivo relevance was documented as IFNκ was one of only two significantly increased type I IFNs in both discoid and subacute subtypes of CLE. Immunohistochemistry confirmed epidermal and dermal expression of IFNκ in CLE.

Conclusion: IFNκ is a novel type I IFN that is produced more abundantly by lupus vs. control keratinocytes. Importantly, it is a regulator of the hyperinflammatory response in lupus keratinocytes and is the most significantly regulated type I IFN in CLE lesions. Our data thus support a regulatory loop in which IFNκ is secreted by lupus keratinocytes and primes them for a robust interferon and inflammatory response following stimulation with microbial ligands or UV. IFNκ may thus serve as a novel and organ-specific target for treatment or prevention of CLE.

Disclosure: J. Stannard, None; T. J. Reed, None; E. Myers, None; L. Lowe, None; M. Sarkar, None; X. Xing, None; C. C. Berthier, None; J. Gudjonsson, None; J. M. Kahlenberg, None.

To cite this abstract in AMA style:

Stannard J, Reed TJ, Myers E, Lowe L, Sarkar M, Xing X, Berthier CC, Gudjonsson J, Kahlenberg JM. Interferon Kappa Is a Novel Type I IFN That Drives Cutaneous Inflammation in Systemic Lupus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/interferon-kappa-is-a-novel-type-i-ifn-that-drives-cutaneous-inflammation-in-systemic-lupus/. Accessed .

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