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Abstract Number: 2408

Comparison of the Tear Cytokine and Chemokine Profile of Children with JIA and JIA-Associated Uveitis

Sheila Angeles-Han1, Virginia Miraldi Utz2, Sherry Thornton3, Alyssa Sproles3, Najima Mwase4, Theresa Hennard3, Mekibib Altaye4 and Gary Holland5, 1Rheumatology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, 2Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, 3Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 4Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 5Jules Stein Eye Institute, Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA

Meeting: ACR/ARHP Annual Meeting 2018

Keywords: Juvenile idiopathic arthritis (JIA) and uveitis

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Session Information

Date: Tuesday, October 23, 2018

Title: Pediatric Rheumatology – Clinical Poster III: Juvenile Idiopathic Arthritis and Uveitis

Session Type: ACR Poster Session C

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

Background/Purpose: Children with JIA are at increased risk for uveitis. Known risk factors do not accurately stratify risk. Biomarkers are needed to predict uveitis development in JIA. Aqueous humor (AqH) has been studied, but the clinical application is limited by the invasive nature of collection. Analysis of tears is a non-invasive approach to better identify children with JIA who are most susceptible to uveitis. Our objective is to compare the tear profiles of children with JIA-associated uveitis (JIA-U) to JIA without uveitis (JIA) for the presence of cytokines and chemokines reported in the AqH of adults and children with uveitis.

Methods: Tears were collected from 16 children with JIA-U and 16 with JIA who were ≥5 years old using Schirmer strips. Cytokine and chemokines reported in the AqH of children with uveitis (IL-18, IL-8/CXCL8, IP-10/CXCL10, MCP-1, RANTES/CCL5, and sICAM-1) were determined using Milliplex™ Multiplex kits (MilliporeSigma, Darmstadt, Germany). A mixed model approach was used where each cytokine outcome is modeled as a function of diagnosis to compare the tear profile of children with JIA to JIA-U.

Results: There were 29 samples from 16 children with JIA-U, and 32 samples from 16 children with JIA. We did not include the unaffected eye of children with JIA-U in the analysis.

Children were primarily Non-Hispanic (93%), White (91%), females (78%) with oligoarticular (72%) or polyarticular rheumatoid factor (RF) negative (28%) JIA. JIA was diagnosed in children with JIA alone at a mean age of 6.7 years (SD 4.2), and in children JIA-U at a mean age of 5.1 years (SD 3.8) (Table 1). Uveitis was diagnosed at a mean age of 6.3 years (SD 4.2).

Levels of IL-8, IP-10, and RANTES were significantly increased in JIA compared to JIA-U (p<0.05) (Table 2). MCP-1 was significantly increased in JIA-U compared to JIA (p<0.05).

Conclusion: In this pilot study, we detected cytokines and chemokines in the tears of children with JIA and JIA-U that were previously identified in AqH. We provide evidence of differences in the tear profile of children with JIA-U and JIA that may differentiate those who develop uveitis. If tears can reflect uveitis activity, similar to AqH, it may be a promising biospecimen for uveitis studies. Use of tears could lead to the discovery of biomarkers for the early detection of uveitis and better prediction models for uveitis onset. Studies in larger cohorts are needed.

 

Table 1. Characteristics of children with JIA alone and JIA-associated uveitis, N (%) unless indicated

 

 

JIA

N = 16

JIA-U

N = 16

Female

13 (81)

12 (75)

Caucasian

16 (100)

13 (81)

Non-Hispanic

16 (100)

14 (88)

JIA Category

 

 

     Oligoarticular JIA

13 (81)

10 (63)

     Polyarticular RF (-) JIA

3 (19)

6 (38)

Age JIA Dx, mean (SD)

6.7 (4.2)

5.1 (3.8)

Duration of JIA, mean (SD)

6.7 (4)

8.0 (4.8)

Active arthritis (yes)

7 (44)

6 (38)

Bilateral

–

13 (81)

Age Uveitis Dx, mean (SD)

N = 13

–

6.3 (4.2)

Active uveitis (yes), anterior chamber cells ≥0.5+/hpf

–

2 (13)

Topical medications

 

 

  Topical steroids

–

12 (75)

  Pressure drops

–

1 (6)

Not on systemic treatment

6 (38)

4 (25)

Medications

 

 

  Methotrexate

4 (25)

8 (50)

  Leflunomide

4 (25)

1 (6)

  Etanercept

4 (25)

0 (0)

  Infliximab

1 (6)

4 (25)

  Adalimumab

1 (6)

3 (19)

  Abatacept

2 (13)

1 (6)

  Tocilizumab

0 (0)

2 (13)

Age at tear collection, mean (SD)

13.3 (4.2)

11.8 (4.7)

 

Table 2. Tear cytokine and chemokine profiles of children with JIA alone and JIA-associated uveitis

 

 

JIA

N=16

JIA-U

N=16

p-value*

IL-8/CXCL8, least square means (SE)

4.0 (0.1)

3.6 (0.1)

0.012

IL-18

3.0 (0.2)

3.4 (0.2)

0.088

IP-10/CXCL-10

7.1 (0.1)

6.7 (0.1)

0.005

RANTES/CCL5

2.9 (0.2)

2.1 (0.2)

0.008

MCP-1,

3.1 (0.2)

3.7 (0.2)

0.027

sICAM-1

9.5 (0.1)

9.3 (0.1)

0.228

* Adjusted for potential correlation between a pair of eyes from same child. MCP-1: monocyte chemoattractant protein; IL: interleukin; IP-10/CXCL10: interferon gamma-induced protein/chemokine (C-X-C motif) ligand; RANTES/CCL5: Regulated on activation, normal T expressed, and secreted/chemokine (C-C motif) ligand; sICAM-1: soluble intracellular adhesion molecule 1

 


Disclosure: S. Angeles-Han, None; V. Miraldi Utz, None; S. Thornton, None; A. Sproles, None; N. Mwase, None; T. Hennard, None; M. Altaye, None; G. Holland, None.

To cite this abstract in AMA style:

Angeles-Han S, Miraldi Utz V, Thornton S, Sproles A, Mwase N, Hennard T, Altaye M, Holland G. Comparison of the Tear Cytokine and Chemokine Profile of Children with JIA and JIA-Associated Uveitis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/comparison-of-the-tear-cytokine-and-chemokine-profile-of-children-with-jia-and-jia-associated-uveitis/. Accessed .
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