title: Dysregulation of anti-inflammatory annexin A1 expression in progressive Crohns Disease.
abstract: BACKGROUND
  Development of inflammatory bowel disease (IBD) involves the interplay of environmental and genetic factors with the host immune system. Mechanisms contributing to immune dysregulation in IBD are not fully defined. Development of novel therapeutic strategies is focused on controlling aberrant immune response in IBD. Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD. However, the role of immunomodulatory factors such as annexin A1 (ANXA1) is not well understood. The goal of this study was to examine the association between ANXA1 and IBD, and the effects of anti-TNF-α, Infliximab (IFX), therapy on ANXA1 expression.
  
  
  METHODS
  ANXA1 and TNF-α transcript levels in PBMC were measured by RT PCR. Clinical follow up included the administration of serial ibdQs. ANXA1 expression in the gut mucosa was measured by IHC. Plasma ANXA1 levels were measured by ELISA.
  
  
  RESULTS
  We found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients. ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders. The IFX therapy also modified the cellular immune activation in the peripheral blood of IBD patients. Decreased expression of ANXA1 was detected in the colonic mucosa of IBD patients with incomplete resolution of inflammation during continuous therapy, which correlated with increased levels of TNF-α transcripts. Gut mucosal epithelial barrier disruption was evident by increased plasma bacterial 16S levels.
  
  
  CONCLUSIONS
  Loss of ANXA1 expression may support inflammation during IBD and can serve as a biomarker of disease progression. Changes in ANXA1 levels may be predictive of therapeutic efficacy.
authors.affiliation: Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, United States of America ; Nanobiotechnology Laboratory, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Angela
authors.initials: A
authors.lastname: Sena
authors.forename: Irina
authors.initials: I
authors.lastname: Grishina
authors.forename: Anne
authors.initials: A
authors.lastname: Thai
authors.forename: Larissa
authors.initials: L
authors.lastname: Goulart
authors.forename: Monica
authors.initials: M
authors.lastname: Macal
authors.forename: Anne
authors.initials: A
authors.lastname: Fenton
authors.forename: Jay
authors.initials: J
authors.lastname: Li
authors.forename: Thomas
authors.initials: T
authors.lastname: Prindiville
authors.forename: Sonia Maria
authors.initials: SM
authors.lastname: Oliani
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
authors.forename: Luiz
authors.initials: L
authors.lastname: Goulart
authors.forename: Sumathi
authors.initials: S
authors.lastname: Sankaran-Walters
mesh_terms: D000328:Adult; D000368:Aged; D017305:Annexin A1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D004269:DNA, Bacterial / Q000097:blood; D004275:DNA, Ribosomal / Q000097:blood; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: D017305:Annexin A1; D000911:Antibodies, Monoclonal; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab