title: Changes in serum adhesion molecules, chemokines, cytokines, and tissue remodeling factors in euthyroid women without thyroid antibodies who are at risk for autoimmune thyroid disease: a hypothesis on the early phases of the endocrine autoimmune reaction.
abstract: BACKGROUND
  The target glands in spontaneous animal models of endocrine autoimmune disease show, prior to the autoimmune reaction, growth and connective tissue abnormalities, whereas the autoimmune reaction is initiated by an early accumulation of macrophages and dendritic cells in the target glands.
  
  
  OBJECTIVE
  The aim of the study was to test the hypothesis that serum factors related to these growth and connective tissue abnormalities and the early accumulation of immune cells, ie, tissue growth/remodeling factors, adhesion molecules, chemokines, and pro- and anti-inflammatory cytokines, are related to thyroid peroxidase autoantibodies (TPO-Abs) seroconversion in subjects at risk to develop autoimmune thyroid disease (AITD).
  
  
  METHODS
  A controlled study on 64 TPO-Ab-negative euthyroid female relatives with at least 1 first- or second-degree relative with documented autoimmune hyper- or hypothyroidism, 32 of whom did and 32 who did not seroconvert to TPO-Ab positivity in 5-year follow-up. The relatives were compared with 32 healthy controls. In all subjects we measured serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL3, CCL4, soluble vascular cell adhesion molecule, soluble intercellular adhesion molecule-1, thrombospondin-1, vascular endothelial growth factor-A, angiopoietin 1 receptor-2, metalloproteinase-13, platelet-derived growth factor-BB, fibronectin, IL-1β, IL-6, TNF-α, IL-10, and growth differentiation factor-15 by multiplex (cytometric bead array) or a single commercial ELISA.
  
  
  RESULTS
  Both seroconverting and nonseroconverting family members showed an up-regulation of fibronectin and a down-regulation of platelet-derived growth factor-BB and the adhesion and migration factors CCL2, CCL4, soluble vascular cell adhesion molecule-1, angiopoietin 1 receptor-2, and metalloproteinase-13. The seroconverters differed from the nonseroconverters by an up-regulation of the proinflammatory compounds Il-1β, IL-6, and CCL3.
  
  
  CONCLUSIONS
  This study shows that euthyroid females within AITD families show a characteristic pattern of abnormalities in serum levels of tissue remodeling factors, growth factors, chemokines, (vascular) adhesion molecules, and cytokines prior to the occurrence of TPO-Abs in serum. The results provide proof of principle that preseroconversion stages and seroconversion to AITD might be predicted using serum analytes related to growth/connective tissue abnormalities and migration/accumulation abnormalities of macrophages and dendritic cells.
authors.affiliation: Department of Immunology, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Beumer
authors.forename: Grigoris
authors.initials: G
authors.lastname: Effraimidis
authors.forename: Roosmarijn C
authors.initials: RC
authors.lastname: Drexhage
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood / Q000209:etiology*; D015815:Cell Adhesion Molecules / Q000097:blood*; D018925:Chemokines / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology; D008875:Middle Aged; D012306:Risk; D013959:Thyroid Diseases / Q000097:blood / Q000209:etiology*; D013961:Thyroid Gland / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D007453:Iodide Peroxidase