title: TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still's Disease and Their Association with Disease Activity and Clinical Manifestations.
abstract: S100A8/A9 has been suggested as a marker of disease activity in patients with adult-onset Still's disease (AOSD). We evaluated the clinical significance of S100A8/A9 as a biomarker and its pathogenic role in AOSD. Blood samples were collected prospectively from 20 AOSD patients and 20 healthy controls (HCs). Furthermore, skin and lymph node biopsy specimens of AOSD patients were investigated for S100A8/A9 expression levels via immunohistochemistry. Peripheral blood mononuclear cells (PBMCs) of active AOSD patients and HCs were investigated for S100A8/A9 cell signals. S100A8/A9, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in active AOSD patients were higher than those of HCs. S100A8/A9 levels correlated positively with IL-1β, TNF-α and C-reactive protein. The inflammatory cells expressing S100A8/A9 were graded from one to three in skin and lymph node biopsies of AOSD patients. The grading for S100A8/A9 was more intense in the skin lesions with karyorrhexis, mucin deposition, and neutrophil infiltration. Like lipopolysaccharide (LPS), S100A8/A9 induced phosphorylation of p38 and c-Jun amino-terminal kinase (JNK) in PBMCs, suggesting that S100A8/A9 activates Toll-like receptor 4 signaling pathways. These findings suggest that S100A8/A9 may be involved in the inflammatory response with induction of proinflammatory cytokines and may serve as a clinicopathological marker for disease activity in AOSD.
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. nakhada@naver.com.
authors.forename: Hyoun-Ah
authors.initials: HA
authors.lastname: Kim
authors.affiliation: Department of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. hanpathol@naver.com.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. kwj881010@hanmail.net.
authors.forename: Woo-Jung
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. simuner@naver.com.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Noh
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. godofpeace@nate.com.
authors.forename: Jeong-Mi
authors.initials: JM
authors.lastname: An
authors.affiliation: Department of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. Huuneeyim@naver.com.
authors.forename: Hyunee
authors.initials: H
authors.lastname: Yim
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. serinne20@hanmail.net.
authors.forename: Ju-Yang
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. yousunkim@ajou.ac.kr.
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 443-380, Korea. chsuh@ajou.ac.kr.
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Suh
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D040501:Calgranulin A / Q000097:blood* / Q000378:metabolism; D040502:Calgranulin B / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015398:Signal Transduction / Q000502:physiology; D016706:Still's Disease, Adult-Onset / Q000097:blood* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D053583:Interleukin-1beta; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: S100A8/A9; adult-onset Still’s disease; biomarker; disease activity; interleukin-1β