Brief Article
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World J Gastroenterol. Mar 14, 2014; 20(10): 2664-2672
Published online Mar 14, 2014. doi: 10.3748/wjg.v20.i10.2664
ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients
Simone CS Wolfkamp, Caroline Verseyden, Esther WM Vogels, Sander Meisner, Kirsten Boonstra, Charlotte P Peters, Pieter CF Stokkers, Anje A te Velde
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
Kirsten Boonstra, Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 BK Amsterdam, The Netherlands
Pieter CF Stokkers, Department of Gastroenterology and Hepatology, St. Lucas Andreas Hospital, 1105 BK Amsterdam, The Netherlands
Author contributions: Wolfkamp SCS, Stokkers PCF and te Velde AA designed the research; Wolfkamp SCS, Verseyden C, Vogels EWM and Meisner S performed the research; Boonstra K and Peters CP contributed to patient work; Wolfkamp SCS Verseyden C and Meisner S analyzed the data; Wolfkamp SCS, Stokkers PCF and te Velde AA wrote the paper.
Correspondence to: Dr. Anje A te Velde, PhD, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, S2-176, Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands. a.a.tevelde@amc.uva.nl
Telephone: +31-20-5668060 Fax: +31-20-5669190
Received: September 6, 2012
Revised: February 1, 2013
Accepted: February 7, 2013
Published online: March 14, 2014
Abstract

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 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.

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.

Keywords: Inflammatory bowel disease, Phagocytosis, Polymorphism, Monocytes, Granulocytes, Nucleotide-binding ligomerization domain-containing protein 2, Immunity-related guanosine triphosphatase gene, Autophagy related like 1