ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2349

Interferon Signature in Childhood Rheumatic Diseases

Hafize Emine Sonmez1, İ. Çağatay Karaaslan2, Ezgi Deniz Batu3, Banu Anlar4, Betul Sozeri5, Adriana Almeida de Jesus6, Raphaela Goldbach-Mansky7 and Seza Ozen8, 1Department of Pediatrics, Divison of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey, 2Department of Molecular Biology, Hacettepe University, Ankara, Turkey, 3Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey, 4Department of Pediatrics, Division of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey, 5Pediatric Rheumatology, Ümraniye Tranning and Research Hospital, İstanbul, Turkey, 6National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, 7Translational Autoinflammatory Disease Studies (TADS), Laboratory of Clinical Investigation and Microbiology (LCIM), NIAID/NIH, Bethesda, MD, 8Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Tuesday, November 7, 2017

Title: Pediatric Rheumatology – Pathogenesis and Genetics Poster

Session Type: ACR Poster Session C

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

Background/Purpose:

Several rheumatic diseases are characterized by overexpression of type I interferon(IFN)-inducible or viral response genes, termed the IFN signature. Recently this signature has been reported in a novel group of monogenic Type-I IFN mediated autoinflammatory diseases(AIDs) or autoinflammatory interferonopathies. We aimed to compare a set of clinical features previously associated with monogenic autoinflammatory AIDs and a blood IFN score with autoimmunue (SLE, JDM) interferonopathies, and other disease controls.

Methods:

We identified 12 patients with probable interferonopathy and selected clinical features of IFN mediated AIDs based on literature review/expert opinion (Table 1). We compared the clinical criteria with 23 controls (8 healthy children, 6 oligoarticuler juvenile idiopathic arthritis[oJIA] patients,4 systemic lupus erythematous[SLE], 5 with DADA2). The expression of 28 IFN-related genes was quantified from RNA from whole blood using NanoString technology. Summary scores for IFN6/IFN28/ and a z-score for CXCL10(IP10) were calculated.

Results:

The mean clinical score was in the presumed IFNopathies(minimum-maximum) 5 (3-7). The median IFN6, IFN28, scores were significantly higher in the probable interferonopathy cases as compared to healthy controls and oJIAs and DADA2 patients but did not differ from SLE patients. Interestingly, CXCL10(IP10) scores were higher(but not significant) in the probable interferonopathy group than the SLE and DADA2 groups.

Conclusion:

We suggest a set of clinical criteria combined with the 6 gene or 28gene IFN score in developing criteria for IFN-mediated AIDs. Development and validation of an appropriate criteria is ongoing.

Table 1. Preliminary clinical score to differentiate interferon(IFN)-mediated autoinflammatory diseases (AIDs) from interleukin-1(IL-1)-mediated AIDs

Clinical preliminary criteria

Presumed

IFN mediated AIDs

n=12

JIA

n=6

SLE

n=4

DADA2

n=5

    1. Skin manifestations (nodular erythema, violaceous plaques in cold-sensitive acral areas)

12/12

0/6

0/4

1/5

    1. Vasculopathy (chill-blain like rash, microangiopathic vasculopathy, gangrene/ulcers/infarcts in acral areas)

6/12

0/6

0/4

1/5

    1. Lipodystrophy

2/12

0/6

0/4

0/5

    1. Joint manifestations (contractures, non-erosive arthritis)

5/12

0/6

0/4

0/5

    1. Myositis (patchy)

2/12

0/6

0/4

0/5

    1. CNS manifestations (basal ganglia calcifications, leukoencephalopathy, white matter disease, L/P lymphocytic findings)

8/12

0/6

0/4

0/5

    1. Pulmonary involvement (interstitial lung disease, pulmonary fibrosis, pulmonary hypertension

2/12

0/6

0/4

0/5

    1. Leukopenia/lymphopenia with flares

4/12

0/6

4/4

1/5

Median clinical score (STD)

5

0

1

0

Median 6-gene IFN score (minimum-maximum)

137.87 (0.251-380.09)

3.17 (-0.08-23.42)

159.66 (-0.22-381.69)

10.25

(2.86-

36.37

Median) 28-gene IFN score (minimum-maximum)

324.01 (24.66-949.98)

18.64 (8.91-95.76)

236.45(2.75-475.96)

60.39

(21.24-

209.29

CXCL10 z-score (STD)

186.07

35.46

52.05

74.97


Disclosure: H. E. Sonmez, None; İ. Ç. Karaaslan, None; E. D. Batu, None; B. Anlar, None; B. Sozeri, None; A. Almeida de Jesus, None; R. Goldbach-Mansky, None; S. Ozen, None.

To cite this abstract in AMA style:

Sonmez HE, Karaaslan İÇ, Batu ED, Anlar B, Sozeri B, Almeida de Jesus A, Goldbach-Mansky R, Ozen S. Interferon Signature in Childhood Rheumatic Diseases [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/interferon-signature-in-childhood-rheumatic-diseases/. Accessed .

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