ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1134

Role of NOD2 Pathway in Sarcoidosis Cases with Characteristics of Blau Syndrome

Gerard Dumancas1, Indra Adrianto2, Albert M. Levin3, Michael C. Iannuzzi4, Benjamin A. Rybicki3 and Courtney Montgomery5, 1Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2825 Ne 13th St. Ms 57, Oklahoma Medical Research Foundation, Oklahoma City, OK, 3Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, 4Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, 5Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Blau syndrome, genetics, nod-like receptor (NLR), sarcoidosis and uveitis

  • Tweet
  • Email
  • Print
Session Information

Title: Genetics, Genomics and Proteomics II

Session Type: Abstract Submissions (ACR)

Background/Purpose: Blau syndrome (BS) is a rare autosomal dominant, autoinflammatory syndrome characterized by the clinical triad symptoms of symmetric arthritis, dermatitis, and granulomatous recurrent uveitis, similar to that of early onset sarcoidosis. The phenotype of the disease has proven to be more complex than initially thought but most commonly involve cutaneous and arthritis manifestations. Eye disease is rarely the presenting symptom but significant visual impairment has been observed in 46% of patients. Polymorphisms in the nucleotide oligomerization domain 2 (NOD2) are known to be associated with susceptibility to BS, Crohn’s disease and sarcoidosis. Studies have shown that dysregulation of NOD2 signaling is involved in the pathogenesis of a variety of inflammatory disorders and has been implicated in the development of autoimmune disease, allergy, and asthma. As such, the goal of our study was to investigate the involvement of the NOD2 pathway genes by selecting sarcoidosis cases that presented with disease similar to BS in African Americans (AAs) and European Americans (EAs).

Methods: Our AA case-case analysis comprised 51 AA sarcoidosis cases with positive skin and bone/joint involvement (~35.3% also have eye involvement), and 255 AA sarcoidosis cases without any skin and bone/joint involvement. Our EA case-case analysis consisted of 27 EA sarcoidosis cases with positive skin and bone/joint involvement (~14.8% have eye involvement), and 135 EA sarcoidosis cases without any skin and bone/joint involvement. Genotyping was performed at the Oklahoma Medical Research Foundation (OMRF) using the Illumina HumanOmni1-Quad array and imputed using IMPUTE2/gtool. Quality control included removal of SNPs with call rate < 80% and Hardy-Weinberg proportion tests P < 0.001. We evaluated 5,362 SNPs in AAs and 2,639 SNPs in EAs from 30 genes within the NOD2 pathway. Single-marker association test was performed using EMMAX adjusted for sex as a covariate. 

Results: We observed novel significant associations in a TAB1 variant in AAs (rs35506409) and TAB2 variants (rs111447766, rs111576955, rs76778446, and rs79995379) in EAs passing Bonferroni thresholds (P < 3.46x10-5 in AAs; P < 1.12x10-4 in EAs). TAB1 is involved in kinase activator activity while TAB2 is involved in polyubiquitin binding molecular functions. Cursory analysis using BioGPS of these genes confirmed their high expression in retina, CD4+ T cells, and CD8+ T cells of human tissues. Previous studies have shown that TAB1 has been found to play a role in skin homeostasis, wound repair, and oncogenesis. Further, both TAB1 and TAB2 genes have been found to be redundantly involved in lipopolysaccharide-induced TAK1 activation in macrophages, and that deletion of either TAB1 or TAB2 results in macrophage death.

Conclusion: Our genetic study of the key players in the NOD2 pathway identified novel genetic associations in TAB1 in AAs and TAB2 in EAs. These findings will give insight into the genetic etiology of BS in adult sarcoidosis cases among AAs and EAs.


Disclosure:

G. Dumancas,
None;

I. Adrianto,
None;

A. M. Levin,
None;

M. C. Iannuzzi,
None;

B. A. Rybicki,
None;

C. Montgomery,
None.

  • Tweet
  • Email
  • Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-nod2-pathway-in-sarcoidosis-cases-with-characteristics-of-blau-syndrome/

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 »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology