title: Differential cytokine expression detected by protein microarray screening in peripheral blood of patients with refractory Graves' disease.
abstract: OBJECTIVE
  The prognosis of Graves' disease (GD) varies among patients. However, the immune pathogenesis of refractory GD is still unknown. The aim of this study was to explore the cytokine expression profile associated with refractory GD.
  
  
  METHODS
  Preliminary cytokine protein microarray screening was performed to detect differentially expressed cytokines in the plasma of four patients with refractory GD and four patients with stable GD. Some differentially expressed cytokines were then validated in plasma by enzyme-linked immunosorbent assay (ELISA) and in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction (qRT-PCR) on another independent set of samples.
  
  
  RESULTS
  We found that 21 cytokines were differentially expressed between patients with intractable GD and those in remission, including 18 upregulated and 3 downregulated cytokines with a fold change >1·30 and <0·77, respectively. Intractability-related elevation of three cytokines (IL-4, IL-6 and IL-10) was validated by ELISA in plasma on another GD cohort with 30 patients in recurrence and 14 in remission (t-test, P = 0·035, 0·033 and 0·041, respectively). Furthermore, mRNA expression of IL-4, IL-6 and IL-10 in PBMCs, detected by qRT-PCR, was significantly elevated in patients with refractory GD compared with those in remission (P = 0·039, 0·047 and 0·042, respectively).
  
  
  CONCLUSIONS
  The severity of GD is associated with the aberrant expression and secretion of several cytokines that may serve as potential biomarkers and predictors for disease prognosis. Targeting these cytokines or their receptors may also lead to a novel therapeutic intervention for GD.
authors: Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Rong-hua
authors: RH
authors: Song
authors: Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Qiu
authors: Q
authors: Qin
authors: Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Xuan
authors: X
authors: Wang
authors: Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Ni
authors: N
authors: Yan
authors: Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Shuai
authors: S
authors: Meng
authors: Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Xiao-hong
authors: XH
authors: Shi
authors: Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Shuang-tao
authors: ST
authors: He
authors: Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China.
authors: Jin-an
authors: JA
authors: Zhang
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006111:Graves Disease / Q000097:blood* / Q000235:genetics / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016753:Interleukin-10; D015847:Interleukin-4