ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2130

Interferon Induced Gene Transcripts Are Differentially Upregulated in the Kidney of Lupus Nephritis Patients Irrespective of Activity or Damage

S. Sam Lim1, Alton B Farris1, Tobias Guennel2, Shiliang Wang3, Jason Cobb1, Dominic Sinibaldi4, Scott Jenks1, Ignacio Sanz1, Xiang Guo3, Gabor Illei5, Kui Shen2, Monica Battle1, Chungwen Wei1 and WI White3, 1Emory University School of Medicine, Atlanta, GA, 2Precision for Medicine, Frederick, MD, 3MedImmune, Gaithersburg, MD, 4MedImmune, Gaithersberg, MD, 5Viela Bio, Gaithersburg, USA, Gaithersberg, MD

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Gene Expression, interferons and nephritis

  • Tweet
  • Email
  • Print
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:  Lupus nephritis (LN) afflicts 12-69% lupus patients. Even with the best available therapies, complete response is achieved in only 10-85% of patients. The risk of nephritis and its poor outcomes is significantly higher in blacks. To gain better understanding of the pathogenesis specific for LN, biopsy samples from LN and other glomerulopathies (controls) were evaluated for differential gene expression levels.

Methods: Patients with LN meeting ACR SLE criteria and controls consented to donate additional samples during a clinically indicated renal biopsy. Forty-one LN and 8 control samples were analyzed after rRNA was depleted from total RNA. Libraries were prepared and sequenced with Illumina HiSeq 2500 and mapped onto the human genome. Differentially expressed genes (DEG) were selected by DESeq2. Signaling Pathway Impact Analysis identified pathways enriched for DEGs that were mapped to the Reactome database. Key transcripts were correlated with clinical and histologic measures. LN samples were scored using the NIH activity (AI) and chronicity indices (CI).

Results: Demographics and glomerular involvement are listed in Table 1.

Pathways enriched for DEGs were only identified for those driven by interferon (IFN): a/b signaling, IFN signaling, and cytokine signaling. Transcripts that overlapped between all 3 of these pathways are presented in Figs. 1 and 2. Interferon pathway expression levels were increased in LN compared to controls for DEG identified transcripts. Key pathways were consistent with or without HIV-infected controls compared to LN. Expression levels for interferon induced transcripts (IIGTs) were persistently elevated in LN patients as compared to controls regardless of degree of LN activity or chronicity (represented by NIHAI high (score>8, range 0-17) vs. low and NIHCI high (score>4, range 2-10) vs. low.

Conclusion: IIGTs are differentially upregulated in LN compared to controls. Within LN, IIGTs are not markedly different between high and low levels of histologic activity or damage. The observation that interferon persists in low activity and high damage LN biopsy samples may represent an opportunity to improve response and outcomes using agents that selectively target IFN pathways.

Table 1: Demographics and glomerular involvement

Lupus Nephritis

n=41

Controls

n=8

Demographics

Gender

n, (%)

female

32 (78.1)

4 (50)

male

9 (21.9)

4 (50)

Race

n, (%)

black

37 (90.2)

5 (62.5)

white

2 (4.9)

3 (37.5)

other

2 (4.9)

0 (0)

Glomerular involvement

Biopsy (years)

mean age at biopsy

34.1

43.3

Duration (years)

SLE

8.7

Lupus Nephritis

n, (%)

class II

6 (14.6)

class III

10 (24.4)

class IV

20 (48.8)

class V

26 (63.4)

class VI

4 (9.8)

Other Glomerulopathies

n, (%)

HIV associated nephropathy

2 (25)

focal segmental glomerulosclerosis

2 (25)

IgA nephropathy

2 (25)

minimal change disease

1 (12.5)

thrombotic microangiopathy

1 (12.5)

diabetic nephropathy

1 (12.5)


Disclosure: S. S. Lim, MedImmune, 2; A. B. Farris, MedImmune, 2; T. Guennel, AstraZeneca, 2; S. Wang, MedImmune, 2; J. Cobb, MedImmune, 2; D. Sinibaldi, MedImmune, 1; S. Jenks, MedImmune, 2; I. Sanz, None; X. Guo, MedImmune, 1; G. Illei, MedImmune, 1; K. Shen, AstraZeneca, 2; M. Battle, MedImmune, 2; C. Wei, None; W. White, AstraZeneca, 1,MedImmune, 3.

To cite this abstract in AMA style:

Lim SS, Farris AB, Guennel T, Wang S, Cobb J, Sinibaldi D, Jenks S, Sanz I, Guo X, Illei G, Shen K, Battle M, Wei C, White W. Interferon Induced Gene Transcripts Are Differentially Upregulated in the Kidney of Lupus Nephritis Patients Irrespective of Activity or Damage [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/interferon-induced-gene-transcripts-are-differentially-upregulated-in-the-kidney-of-lupus-nephritis-patients-irrespective-of-activity-or-damage/. Accessed February 2, 2023.
  • Tweet
  • Email
  • Print

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-induced-gene-transcripts-are-differentially-upregulated-in-the-kidney-of-lupus-nephritis-patients-irrespective-of-activity-or-damage/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2023 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences