ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

• Published in: World journal of gastroenterology : WJG 2014-03, Vol.20 (10), p.2664-2672
• Main Authors: Wolfkamp, Simone C S, Verseyden, Caroline, Vogels, Esther W M, Meisner, Sander, Boonstra, Kirsten, Peters, Charlotte P, Stokkers, Pieter C F, te Velde, Anje A
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autophagy-Related Proteins; bowel; Brief; Carrier Proteins - genetics; Case-Control Studies; Colitis, Ulcerative - genetics; Colitis, Ulcerative - microbiology; Crohn Disease - genetics; Crohn Disease - microbiology; disease; Female; Genetic Predisposition to Disease; Granulocytes - microbiology; Heterozygote; Homozygote; Humans; Inflammatory; Male; Monocytes - microbiology; Nod2 Signaling Adaptor Protein - genetics; Phagocytosis; Phagocytosis - genetics; Phenotype; Polymorphi; Polymorphism, Genetic; Severity of Illness Index; Young Adult
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v20.i10.2664

AIM: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 immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(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.CONCLUSION: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.