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P007. The ratio of circulating estrogen receptors beta and alpha (ERβ/ERα) indicates endoscopic activity in patients with Crohn's disease

P.M. Linares1, A. Algaba2, M. Chaparro1, A. Urzainqui3, M. Guijarro-Rojas4, J.P. Gisbert1, F. Bermejo2, M.E. Fernández-Contreras1, 1Hospital Universitario de La Princesa, IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 2Hospital Universitario de Fuenlabrada, Gastroenterology Unit, Fuenlabrada, Spain, 3Hospital Universitario de La Princesa and IP, Immunology Unit, Madrid, Spain, 4Hospital Universitario de La Princesa and IP, Pathology Unit, Madrid, Spain

Background

Estrogen receptors alpha (ERα) and beta (ERβ) are involved in biological processes including inflammation, proliferation or angiogenesis, related with immune-mediated conditions like inflammatory bowel disease (IBD), but their effects are antagonistic. Thus, it has been suggested that the net action of estrogens might depend on the relative proportion of both ERs. The aim of the present study was to determine the possible association between the ratio of circulating ERβ and ERα (ERβ/ERα) and IBD development and activity.

Methods

A retrospective study was performed in serum samples from patients with IBD and healthy volunteers. Serum ERα and ERβ were measured by ELISA (Shanghai Sunred Biological Technology Co. China). Clinical IBD activity was assessed respectively by the Mayo score for ulcerative colitis (UC), and by the Harvey–Bradshaw index for Crohn's disease (CD). Endoscopic activity was determined with the Mayo subscore and the SES-CD index. Previous history of allergy and/or autoimmune disorders was an exclusion criterion in the control group.

Results

207 serum samples from 39 controls (24 females and 15 males) and 169 patients with IBD (94 CD and 75 UC) were analyzed. The mean age of patients with IBD was 35±9 years; 51% were female. Clinical and endoscopic disease activity was observed respectively in 33% and 59% patients. ERβ/ERα did not differ between patients and controls (1.1±0.5 vs. 1.0±0.2), or with type of IBD, age, sex, or clinical activity (data not shown), but was significantly lower in patients with endoscopic activity (P < 0.05; Table 1). This association was stronger in the CD group (P = 0.006), but was not seen in patients with UC. In the ROC curve analysis, an ERβ/ERα ratio lower than 1.0 (cut-off value) was suggestive of endoscopic activity in patients with CD (area under the curve: 0.83; sensitivity and specificity: 75%).

Table 1
AllCDUC
Endoscopic activityERβ/ER α*P-valueERβ/ER α*P-valueERβ/ER α*P-value
Inactive1.1±0.4<0.051.4±0.60.0061.0±0.21.0
Active0.9±0.3 0.9±0. 1.0±0.4
*Ratio ± standard deviation.

Conclusion

Circulating levels of ERs are not related with the development or type of IBD. The ERβ/ERα ratio is associated with endoscopic activity in patients with CD, but not in those with UC. An ERβ/ERα ratio lower than 1.0 suggests endoscopic activity in patients with CD.