title: CXCL13, CCL4, and sTNFR as circulating inflammatory cytokine markers in primary and SLE-related autoimmune hemolytic anemia.
abstract: BACKGROUND
  A considerable proportion of autoimmune hemolytic anemia (AIHA) are secondary to underlying autoimmune disorders, especially syetemic lupus erythematosus (SLE), and the clinical and laboratory index for early discrimination between primary and SLE-related AIHA has yet to be defined. In the present study, we proposed novel cytokine patterns in the pathogenesis of AIHA as well as parameters for the timely identification of SLE-related patients.
  
  
  METHODS
  AIHA patients confirmed by immunohematology techniques from September 2010 to December 2012 in our facility were consecutively included and categorized into primary (n = 19) and SLE-related (n = 18) groups. Plasma cytokine profiles were measured in a single procedure by Quantibody Human Inflammatory Array 1 (RayBiotech, Norcross, GA).
  
  
  RESULTS
  SLE-related AIHA patients demonstrated younger age (39 ± 20 vs.57 ± 16 years, p = 0.004), poorer reticulocyte compensation (6.8 ± 7.1 vs.12.2 ± 8.6%, p = 0.045), lower levels of lactate dehydrogenase [361 (265-498) vs. 622 (387-1154) U/L, p = 0.004], and higher occurrence of anticardiolipin antibody [9/18 (50%) vs. 2/19 (10.9%), p = 0.009]. MCP-1/CCL2, MIP-1β/CCL4, BLC/CXCL13, IL-8/CXCL8, sTNFRI, and sTNFRII were significantly up-regulated in both groups, while sTNFRII was remarkably higher in SLE-related patients. Among both groups, hemoglobin level was negatively correlated with CXCL13 (r = -0.332, p = 0.044), while reticulocyte count was positively correlated with CCL4 (r = 0.456, p = 0.005).
  
  
  CONCLUSIONS
  CXCL13 and CCL4 could act as circulating biomarkers in AIHA, and indicated disease severity and erythroid compensation, respectively. Higher plasma sTNFRII might favor the diagnosis of SLE-related instead of primary AIHA.
authors.affiliation: Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China. wu.boting@zs-hospital.sh.cn.|Department of Transfusion, Zhongshan Hospital Fudan University, Shanghai, 200032, China. wu.boting@zs-hospital.sh.cn.
authors.forename: Boting
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China. wang.weiguang@zs-hospital.sh.cn.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China. zhan.yanxia@zs-hospital.sh.cn.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China. li.feng@zs-hospital.sh.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China. zou.shanhua@zs-hospital.sh.cn.
authors.forename: Shanhua
authors.initials: S
authors.lastname: Zou
authors.affiliation: Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan Universiy, Shanghai, 201700, China. qpsunlh023@126.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China. yfcheng@fudan.edu.cn.|Biomedical Research Center, Zhongshan Hospital Fudan Universiy, Shanghai, 200032, China. yfcheng@fudan.edu.cn.|Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan Universiy, Shanghai, 201700, China. yfcheng@fudan.edu.cn.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood* / Q000150:complications; D015415:Biomarkers / Q000097:blood; D054407:Chemokine CCL4 / Q000097:blood*; D054382:Chemokine CXCL13 / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012995:Solubility
chemical_list: D015415:Biomarkers; C066507:CCL4 protein, human; C110663:CXCL13 protein, human; D054407:Chemokine CCL4; D054382:Chemokine CXCL13; D016207:Cytokines; D006454:Hemoglobins; D018836:Inflammation Mediators; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II