Investigation of B-Cell Activating Factor Expression and Its Role in Radiationenteritis

Radiation enteritis is one of the complications during the abdominal or pelvic tumors radiotherapy. However, the mechanism is not clear, some studies revealed that the radiation enteritis maybe related to the inflammation response that caused by the cell damage of intestine tissue. B-cell activating factor (BAFF) is a TNF family protein, BAFF is usually expressed by activating B cells during inflammation. The role of BAFF has been clarified in the several human diseases that related to the inflammation. However, the mechanisms of BAFF on radiation enteritis are worth to evaluate. In this project, we will evaluate the role of BAFF on radiation enteritis. Our protocols were reviewed and approved by the institutional review board of our hospital (TMU-JIRB No. 201409042). Till now, 24 paired serum samples from patients with low pelvic irradiation (before and after) were enrolled in our study. The preliminary data showed BAFF elevated in these patients with pelvic irradiated with 36 Gy. The phenomenon was only noted in small bowel irradiated and there was no BAFF elevated in animal models of radiation pneumonitis or radiation to legs. These findings demonstrated BAFF is specific to small bowel irradiation, and the tissue-specific marker might be found. Based on the preliminary data, the association of clinical samples, clinical findings and animal model of small bowel irradiation will be assessed in the current project. The clinical complications of radiation enteritis might be relieved by anti-BAFF antibody. The possibility will also be evaluated by our animal model of radiation enteritis for preventive or therapeutic effects. In this project, the aim, strategies and methodologies are as followings: 1. Estimate the clinical findings in our patients such as radiation enteritis, complications and BAFF value in our patients with different dose-volume irradiation to small bowel. 2. Estimate the clinical findings in our animal model such as radiation enteritis, pathologic findings, complications and BAFF value in our patients with different dose-volume irradiation to small bowel. 3. Clarify and compare the pathological status between control antibody and BAFF neutralizing antibody treated groups in radiation enteritis animal model. 4. Clarify the cytokine,chemokine and angiogenesis factors expression patterns in the intestinal tissue and by protein arrays and compare those between control antibody and BAFF neutralizing antibody treated groups. Clarify the types and ratio of different immune cells in the intestinal tissue by specific surface marker staining based flow cytometric analysis and compare them between control antibody and BAFF neutralizing antibody treated groups. Realize the relationships among pathology, certain cytokine, chemokine, angiogenesis factors and immune cells to clarify the molecular mechanisms of BAFF on radiationenteritis. In the study, we can clarify the molecular mechanisms of BAFF in radiation enteritis may have help to design the BAFF related molecular therapy to prevent or attenuate radiationenteritis.