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P014. The effect of the anti-TNFα adalimumab on the levels of angiogenic factors in mucosal cultures from patients with inflammatory bowel disease (IBD)

P.M. Linares1, M.E. Fernández-Contreras1, A. Algaba2, M. Chaparro1, F. Bermejo2, J.P. Gisbert1, 1Hospital Universitario de La Princesa, IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 2Hospital Universitario de Fuenlabrada, Gastroenterology Unit, Fuenlabrada, Spain

Background

Effectiveness of adalimumab (ADA) treatment could be related to the modification of different angiogenic proteins, including VEGFA, Ang1, Ang2 and their receptor Tie2. The aim of our study is to compare the concentrations of several angiogenic factors in colonic mucosa culture supernatant (MCS) in patients with IBD and matched controls and to analyze their modifications with the in vitro ADA addition to the culture.

Methods

Prospective study in patients with IBD and non-IBD controls that underwent endoscopy. Duplicates of colonic mucosa samples from affected and non-affected mucosa from each IBD patient were obtained for comparison. Both were washed and then cultured at 37°C in 5% CO2 medium under shaking for 24hours. In one duplicate, ADA was added up to a final concentration of 10 µg/mL prior to culture. MCS levels in AP were determined by ELISA. Endoscopic ulcerative colitis (UC) and Crohn's disease (CD) activity was ascertained by Mayo sub-score and SES-CD indexes, respectively.

Results

28 patients with IBD (16 UC, 12 CD) and 21 controls were included. Mean age was 41±16 years, and 61% were women. The mean disease duration was 7±7 years. According to endoscopic activity, 36% of patient had quiescent, 32% mild, 28% moderate, and 4% severe activity. All angiogenic factors mean levels in MCS were higher in affected than in non-affected MCS; VEGFA (19.1±18.7 versus 8.7±10.5 pg/mL/mg) and Ang2 (21.3±15.7 versus 11.8±8.9 pg/mL/mg) (p < 0.05). There were no differences in MCS depending on endoscopic activity. Levels of VEGFA, Ang1 and Ang2 from the affected, and VEGFA and Tie2 from the non-affected mucosa, were lower when cultured with ADA than without it (Table 1).

In UC patients, VEGFA and Ang1, and all angiogenic factors MCS mean levels were lower in the affected-mucosa and non-affected mucosa, and in the non-affected mucosa when cultured with ADA, respectively (Table 2).

In contrast, in CD patients there were no differences in MCS angiogenic factors levels and the addition of ADA to the culture.

Table 1. Levels of angiogenic factors in MCS from IBD patients after culture
Affected mucosaAffected mucosa + ADAp-valueNon-affected mucosaNon-affected mucosa + ADAp-value
VEGFA19.1±18.714.6±14.50.0038.6±10.55.8±6.10.027
Ang115.7±8.812.2±6.20.02112.5±9.39.1±7.10.069
Ang221.3±15.719.4±13.10.02111.8±8.910.4±6.70.406
Tie212.0±5.512.4±16.10.9118.8±7.05.3±5.20.021
Concentrations are expressed in pg/mL per mg of tissue.
Table 2. Levels of angiogenic factors in MCS from CD patients after culture
Affected mucosaAffected mucosa + ADAp-valueNon-affected mucosaNon-affected mucosa + ADAp-value
VEGFA20.4±13.915.7±10.90.0157.0±7.25.0±6.00.015
Ang118.2±9.613.8±6.40.04913.0±9.68.7±5.80.020
Ang227.2±14.625.7±10.90.74314.5±9.812.2±7.80.001
Tie212.7±4.614.7±18.80.7207.5±3.74.4±3.10.026
Concentrations are expressed in pg/mL per mg of tissue.

Conclusion

ADA might downregulate the production of angiogenic factors in MCS. ADA addition to mucosal cultures affects angiogenic factors levels in samples from patients with UC differently than in patients from CD.