title: Association of CXCL10 and CXCL13 levels with disease activity and cutaneous manifestation in active adult-onset Still's disease.
abstract: BACKGROUND
  C-X-C motif chemokine 10 (CXCL10) is produced in response to interferon-γ, and tumor necrosis factor-α (TNF-α) triggers the accumulation of activated lymphocytes. CXCL13 is constitutively expressed in secondary lymphoid tissues, and the expression is upregulated by TNF-α, via T cell stimulation. It appears that CXCL10 and CXCL13 could play a potential role in the pathogenesis of adult-onset Still's disease (AOSD), therefore, we investigated the associations between CXCL10 and CXCL13 levels and clinical manifestations in patients with active AOSD.
  
  
  METHODS
  Blood samples were collected from 39 active AOSD patients, 32 rheumatoid arthritis (RA) patients and 40 healthy controls (HC). Of the AOSD patients, follow-up samples were collected from 15 9.6 ± 9.2 months later. Serum levels of CXCL10 and CXCL13 were determined using enzyme-linked immunosorbent assay. CXCL10, CXCL13, and C-X-C chemokine receptor type 3 (CXCR3) expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes were investigated via immunohistochemistry.
  
  
  RESULTS
  The CXCL10 levels in AOSD patients (1,031.3 ± 2,019.6 pg/mL) were higher than in RA (146.3 ± 91.4 pg/mL, p = 0.008) and HC (104.4 ± 47.9 pg/mL, p = 0.006). Also, the CXCL13 levels of AOSD patients (158.8 ± 151.2 pg/mL) were higher than those of RA (54.4 ± 61.1 pg/mL, p < 0.001) and HC (23.5 ± 18.1 pg/mL, p < 0.001). Serum CXCL10 levels correlated with ferritin and systemic scores. Serum CXCL13 levels correlated with those of hemoglobin, C-reactive protein, ferritin, and albumin, and systemic scores. In follow-up AOSD patients, the levels of CXCL10 and CXCL13 fell significantly (153.7 ± 130.1 pg/mL, p = 0.002, and 89.1 ± 117.4 pg/mL, p = 0.001, respectively). On immunohistochemistry, the percentages of inflammatory cells expressing CXCL10 ranged from 1 to 85%, CXCL13 from 1 to 72%, and CXCR3 from 2 to 65%. The percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples exhibiting mucin deposition than in those that did not (p = 0.01). CXCL13 levels were correlated with those of CD4 and CD68.
  
  
  CONCLUSIONS
  Serum CXCL10 and CXCL13 levels may serve as clinical markers for assessment of disease activity in AOSD. CXCL10/CXCR3 and CXCL13 may contribute to the inflammatory response, especially skin manifestations thereof, in AOSD.
authors.affiliation: Department of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, South Korea. hanpathol@naver.com.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, South Korea. chsuh@ajou.ac.kr.
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Suh
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, South Korea. serinne20@hanmail.net.
authors.forename: Ju-Yang
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, South Korea. coolfall@nate.com.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Nam
authors.affiliation: Department of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, South Korea. kjefullup@naver.com.
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, South Korea. hyuneeyim@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, South Korea. nakhada@naver.com.
authors.forename: Hyoun-Ah
authors.initials: HA
authors.lastname: Kim
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood / Q000276:immunology*; D054382:Chemokine CXCL13 / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012871:Skin Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016706:Still's Disease, Adult-Onset / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; C110663:CXCL13 protein, human; D054357:Chemokine CXCL10; D054382:Chemokine CXCL13