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Gene variants suggest Crohn’s disease patients receive stronger therapy
European researchers identified genetic traits that can be used to identify patients with Crohn’s disease who may be appropriate for more aggressive treatments, according to recent study data.
Researchers studied 179 patients with Crohn’s disease (CD) and measured their bacterial DNA (bactDNA), tumor necrosis factor-alpha (TNF-a), interferon gamma, IL-12p40, and free serum infliximab and adalimumab levels. They also genotyped the patients’ CD-related nucleotide-binding oligomerization domain containing 2 (NOD2) and ATG16L1 variants, and blood neutrophils were analyzed for phagocytic and bactericidal activity.
BactDNA was present in 44.2% of patients with active CD (Crohn’s Disease Activity Index >150) compared with 23.5% of patients with remitting disease (P=.01). Univariate analysis showed that bactDNA was associated with disease activity (OR=2.6; 95% CI, 1.3-5.4). Patients with NOD2 (OR=4.8; 95% CI, 1.1-13.2) or ATG16L1 (OR=2.4; 95% CI, 1.4-4.7) variants also showed associations when bacterial DNA existed. In patients with both variant genotypes, OR was 12.6 (95% CI, 1.4-4.7).
Researchers also determined:
- Bacterial DNA translocation was directly associated with disease activity and increased the risk of relapse at 6 months.
- Patients with NOD2 showed significantly reduced phagocytic and bactericidal activities, increased serum TNF-a levels in response to bactDNA and significantly decreased levels of free anti-TNF-a.
“Our results identify a subgroup of patients with an increased risk of bacterial DNA translocation and, very likely, an increased risk of relapse,” the researchers wrote. “Classical anti-TNF-a therapy regimens are likely to decrease their efficacy in controlling the risk of flare-up in these patients who might require more aggressive therapeutic programs to reduce inflammation and episodes of bacterial DNA translocation.”
Disclosure: The researchers report no relevant financial disclosures.