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Abstract Number: 2121

Serum High Type I Interferon Is Associated with Active Proliferative Lupus Nephritis in Lupus Patients Accompanied with High Interferon Signature Gene Expression and Plasmacytoid Dendritic Cell Infiltration in Lupus Nephritis Kidney

Taro Iwamoto1, Jessica M. Dorschner2, Mark A. Jensen1, Shanmugapriya Selvaraj3, Danielle Vsetecka2, Shreyasee Amin2, Ashima Makol2, Floranne C. Ernste2, Thomas Osborn2, Kevin Moder2, Vaidehi R. Chowdhary2, Valeria Mezzano4, Peter M. Izmirly5, H. Michael Belmont5, Robert M. Clancy1, Jill P. Buyon1, Ming Wu3, Cynthia A. Loomis3 and Timothy B. Niewold1, 1Colton Center for Autoimmunity, New York University, New York, NY, 2Mayo Clinic College of Medicine, Rochester, MN, 3Department of Pathology, New York University, New York, NY, 4Division of Cardiology, New York University, New York, NY, 5Division of Rheumatology, New York University, New York, NY

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Apoptosis, Dendritic cells, interferons, lupus nephritis and systemic lupus erythematosus (SLE)

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Session Information

Date: Tuesday, October 23, 2018

Session Title: Systemic Lupus Erythematosus – Etiology and Pathogenesis Poster III

Session Type: ACR Poster Session C

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

Background/Purpose: Despite recent advancements in immunosuppressive therapies, lupus nephritis (LN) remains one of the most severe organ manifestations in systemic lupus erythematosus (SLE). High type I interferon (IFN) is a heritable risk for SLE, and 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 plays a critical role in the pathogenesis of LN.

Methods: We studied 221 European-American SLE patients and measured IFN in sera by performing WISH IFN bioassay as described previously. Subtypes of LN were confirmed by renal biopsy review. Complement, anti-dsDNA and other serological parameters were measured in the clinical laboratory, and standard clinical cut-offs were used to define a positive result. mRNA in situ hybridization was performed to detect IFN induced gene (IIG) expression and plasmacytoid dendritic cells in LN kidney biopsies, and Visiopharm analysis software was used for quantitative analysis. Real-time PCR was performed to measure pro-apoptotic gene expressions in human podocyte cell lines. Non-parametric analyses were used unless otherwise mentioned.

Results: Proliferative LN was significantly more common among patients with high serum type I IFN compared to patients with low levels of IFN (p<0.001, OR=3.0, Fisher’s exact test). Notably, IFN level was significantly higher in active proliferative LN compared to inactive proliferative LN (p<0.001), and these findings were independent of complements and anti-dsDNA antibody levels. mRNA in situ hybridization showed increased expression of IIG accompanying plasmacytoid dendritic cell infiltration in active proliferative LN kidneys. In vitro experiments demonstrated that type I IFN induced pro-apoptotic gene expression in human podocyte cell lines.

Conclusion: Our data support an association between type I IFN and active proliferative lupus nephritis that is independent of conventional parameters such as complements 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 proliferative LN in SLE patients.


Disclosure: T. Iwamoto, None; J. M. Dorschner, None; M. A. Jensen, None; S. Selvaraj, None; D. Vsetecka, None; S. Amin, None; A. Makol, None; F. C. Ernste, None; T. Osborn, None; K. Moder, None; V. R. Chowdhary, None; V. Mezzano, None; P. M. Izmirly, None; H. M. Belmont, None; R. M. Clancy, None; J. P. Buyon, None; M. Wu, None; C. A. Loomis, None; T. B. Niewold, EMD Serono, 2.

To cite this abstract in AMA style:

Iwamoto T, Dorschner JM, Jensen MA, Selvaraj S, Vsetecka D, Amin S, Makol A, Ernste FC, Osborn T, Moder K, Chowdhary VR, Mezzano V, Izmirly PM, Belmont HM, Clancy RM, Buyon JP, Wu M, Loomis CA, Niewold TB. Serum High Type I Interferon Is Associated with Active Proliferative Lupus Nephritis in Lupus Patients Accompanied with High Interferon Signature Gene Expression and Plasmacytoid Dendritic Cell Infiltration in Lupus Nephritis Kidney [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/serum-high-type-i-interferon-is-associated-with-active-proliferative-lupus-nephritis-in-lupus-patients-accompanied-with-high-interferon-signature-gene-expression-and-plasmacytoid-dendritic-cell-infilt/. Accessed May 19, 2022.
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