title: ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn's disease patients.
abstract: OBJECTIVE
  To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn's disease (CD).
  
  
  METHODS
  In this study, we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls. As both autophagy related like 1 (ATG16L1) and immunity-related guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleotide-binding ligomerization domain-containing protein 2 (NOD2) has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction. The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo™ Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.
  
  
  RESULTS
  In this study, we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity (ratio of mean fluorescence intensity) between the patient groups and the healthy controls. CD patients show a significantly higher phagocytic capacity (ratio mean percentage of phagocytic cells) compared to healthy controls (51.91% ± 2.85% vs 37.67% ± 7.06%, P = 0.05). The extend of disease was not of influence. However, variants of ATG16L1 (WT: 2.03 ± 0.19 vs homozygoot variant: 4.38 ± 0.37, P < 0.009) as well as NOD2 (C-ins) (heterozygous variant: 42.08 ± 2.94 vs homozygous variant: 75.58 ± 4.34 (P = 0.05) are associated with the phagocytic activity in patients with CD.
  
  
  CONCLUSIONS
  Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants. This could be part of the pathophysiological mechanism resulting in the disease.
authors.affiliation: Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Charlotte P Peters, Anje A te Velde, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Simone C S
authors.initials: SC
authors.lastname: Wolfkamp
authors.affiliation: Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Charlotte P Peters, Anje A te Velde, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Verseyden
authors.affiliation: Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Charlotte P Peters, Anje A te Velde, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Esther W M
authors.initials: EW
authors.lastname: Vogels
authors.affiliation: Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Charlotte P Peters, Anje A te Velde, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Meisner
authors.affiliation: Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Charlotte P Peters, Anje A te Velde, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Boonstra
authors.affiliation: Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Charlotte P Peters, Anje A te Velde, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Charlotte P
authors.initials: CP
authors.lastname: Peters
authors.affiliation: Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Charlotte P Peters, Anje A te Velde, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Pieter C F
authors.initials: PC
authors.lastname: Stokkers
authors.affiliation: Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Charlotte P Peters, Anje A te Velde, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 1105 BK Amsterdam, The Netherlands.
authors.forename: Anje A
authors.initials: AA
authors.lastname: te Velde
mesh_terms: D000293:Adolescent; D000328:Adult; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics / Q000382:microbiology; D003424:Crohn Disease / Q000235:genetics* / Q000382:microbiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006098:Granulocytes / Q000382:microbiology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009000:Monocytes / Q000382:microbiology*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010587:Phagocytosis / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
keywords: Autophagy related like 1; Granulocytes; Immunity-related guanosine triphosphatase gene; Inflammatory bowel disease; Monocytes; Nucleotide-binding ligomerization domain-containing protein 2; Phagocytosis; Polymorphism