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Abstract Number: 1662

High Type I Interferon Activity Is Associated with Active Class Ⅲ/Ⅳ Lupus Nephritis in European-American Lupus Patients Independent of dsDNA Antibodies

Taro Iwamoto1, Jessica M. Dorschner2, Mark A. Jensen1, Danielle Vsetecka2, Shreyasee Amin3, Ashima Makol4, Floranne C. Ernste5, Thomas Osborn3, Kevin Moder3, Vaidehi Chowdhary6 and Timothy B. Niewold1, 1Colton Center for Autoimmunity, New York University, New York, NY, 2Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, MN, 3Rheumatology, Mayo Clinic, Rochester, MN, 4Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, 5Division of Rheumatology, Mayo Clinic Rochester, Rochester, MN, 6Internal Medicine, Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: interferons and lupus nephritis, Lupus

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Session Information

Date: Monday, November 6, 2017

Session Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Lupus nephritis (LN) is one of the most severe types of organ involvement in systemic lupus erythematosus (SLE), despite the recent advances in immunosuppressive therapies. High type Ⅰ interferon (IFN) is a heritable risk for SLE, and some previous studies have suggested a link between high IFN and lupus nephritis. However, little is known about the relationships between high levels of IFN and the subtypes of LN, and whether IFN is more associated with anti-dsDNA antibodies or with clinical nephritis.

Methods: We studied 197 EA SLE patients and measured type Ⅰ IFN in sera by performing WISH IFN bioassay as described previously. Subtypes of LN were confirmed by renal biopsy review. Complements, anti-dsDNA and other auto-antibodies were measured in the clinical laboratory, and standard clinical cut-offs were used to define a positive result. Non-parametric analyses were used to compare IFN data with the antibody data.

Results: IFN level and SLEDAI score was positively correlated (r=0.30, p<0.0001, Spearman) in our cross-sectional evaluation. EA subjects with a high levels of IFN (IFN score ≥2) were more likely to have renal manifestations compared to the subjects with a low levels of IFN(IFN score <2) (p<0.001, OR=3.4, Fisher’s exact test). In addition, the incidence rate of class Ⅲ/Ⅳ LN was significantly higher among patients with a high levels of IFN compared to the patients with low levels of IFN (p=0.0197, OR=5.1, Fisher’s exact test). Notably, IFN level was significantly higher in active class Ⅲ/Ⅳ LN compared to inactive class Ⅲ/Ⅳ LN (p<0.001 Mann-Whitney U) and this was not observed in non-class Ⅲ/Ⅳ LN populations.. Positivity of ds-DNA antibody did not show significant difference between inactive class Ⅲ/Ⅳ LN and active class Ⅲ/Ⅳ LN, and the correlation between SLEDAI and IFN was driven by the dsDNA and complement variables.

Conclusion: Our data support an association between type I IFN and class III/IV nephritis that is independent of overall SLEDAI and anti-dsDNA antibodies, suggesting that IFN is involved in renal pathogenesis. These data also suggest that IFN could predict renal disease activity or the future risk of developing LN, especially class Ⅲ/Ⅳ LN in EA SLE patients.


Disclosure: T. Iwamoto, None; J. M. Dorschner, None; M. A. Jensen, None; D. Vsetecka, None; S. Amin, None; A. Makol, None; F. C. Ernste, None; T. Osborn, None; K. Moder, None; V. Chowdhary, None; T. B. Niewold, None.

To cite this abstract in AMA style:

Iwamoto T, Dorschner JM, Jensen MA, Vsetecka D, Amin S, Makol A, Ernste FC, Osborn T, Moder K, Chowdhary V, Niewold TB. High Type I Interferon Activity Is Associated with Active Class Ⅲ/Ⅳ Lupus Nephritis in European-American Lupus Patients Independent of dsDNA Antibodies [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/high-type-i-interferon-activity-is-associated-with-active-class-%e2%85%a2%e2%85%a3-lupus-nephritis-in-european-american-lupus-patients-independent-of-dsdna-antibodies/. Accessed January 19, 2021.
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