TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still's Disease and Their Association with Disease Activity and Clinical Manifestations

Hyoun-Ah Kim¹, In Je Kim², Jae Ho Han³, Juyang Jung⁴, Chang-Hee Suh⁴ and You-Sun Kim⁵, ¹Department of Rheumatology, Ajou University School of Medicine, Suwan, South Korea, ²Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, South Korea, ³Department of Pathology, Ajou University School of Medicine, Suwon, South Korea, ⁴Department of Rheumatology, Ajou University School of Medicine, Suwon, South Korea, ⁵Department of Biochemistry and Molecular biology, Ajou University School of Medicine, Suwon, South Korea

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Adult-onset Still's disease

Session Information

Date: Sunday, November 8, 2015

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: S100A8 and S100A9 are two calcium-binding proteins that belong to the S100 family, and those are expressed by infiltrating monocytes and neutrophils under inflammatory conditions. S100A8/A9 has been suggested as biomarkers of disease activity in patients with systemic juvenile idiopathic arthritis or adult-onset Still’s disease (AOSD). We investigated the clinical significance and the pathogenic role of this marker in AOSD.

Methods: Serum samples were prospectively collected from 20 active AOSD patients, 20 rheumatoid arthritis (RA), and 20 healthy controls (HC). S100A8/A9 expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes and 8 AOSD with lymphadenopathy were investigated via immunohistochemistry. Each marker was recorded as the numbers of positive inflammatory cells divided by the numbers of total inflammatory cells, then expressed as a graded on a scale from 1 to 3: 1,1-33%; 2, 34-66%,; 3, 67-100%. Peripheral blood mononuclear cells (PBMC) from active AOSD and HC were evaluated for interleukin-1β (IL-1β) release, and in vitro study with PBMC and human acute monocytic leukemia (THP-1) cell line was done for cell signal of S100A9 or S100A8/A9.

Results: S100A8/A9 levels of active AOSD (15.43 ± 7.3 μg/mL) were higher than those of RA (4.04 ± 4.18 μg/mL, p<0.001) and HC (2.01 ± 1.06 μg/mL, p<0.001). The IL-1β and TNF- α levels of AOSD were higher than those of HC. Serum S100A8/A9 levels correlated with IL-1β (r=0.603, p<0.001), TNF- α (r=0.405, p=0.009), ferritin (r=0.698, p<0.001), and CRP (r=0.811, p<0.001). The grade of inflammatory cells expressing S100A8/A9 ranged variably from 1 to 3 in skin and lymph node biopsies of active AOSD. The grading and strength of staining of the positive cells in S100A8/A9 was more intense for karyrrhexis (p=0.028), mucin deposition (p=0.014), and neutrophil infiltration (p=0.006). S100A9 in serum of patients with AOSD was a strong inducer of IL-1β expression in PBMC. S100A9 induced signal transduction pathways, including JNK and p38 in PBMC from AOSD patients and HC.

Conclusion: The data suggest that S100A8/A9 may contribute to the inflammatory response by induction of inflammatory cytokines, and serve as clinicopathologic markers for assessment of disease activity in AOSD.

Disclosure: H. A. Kim, None; I. J. Kim, None; J. H. Han, None; J. Jung, None; C. H. Suh, None; Y. S. Kim, None.

To cite this abstract in AMA style:

Kim HA, Kim IJ, Han JH, Jung J, Suh CH, Kim YS. TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still’s Disease and Their Association with Disease Activity and Clinical Manifestations [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/tlr4-endogenous-ligand-s100a8a9-levels-in-adult-onset-stills-disease-and-their-association-with-disease-activity-and-clinical-manifestations/. Accessed .

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