HIGH COPY NUMBER POLYMORPHISMS OF ALPHA DEFENSIN 1-3 ARE ASSOCIATED WITH THERAPEUTIC RESPONSIVENESS IN INFLAMMATORY BOWEL DISEASE

BACKGROUND AND PURPOSE Prednisolone therapy is the first choice for the treatment of acute severe ulcerative colitis (ASUC), however, the refractory case is sometimes observed. Alpha defensin 1-3 (DEFA1A3) stored in neutrophils acts as an effector factor of innate immunity. It has been reported that the copy number variation of the DEFA1A3 gene is associated with the severity of ulcerative colitis (UC). However, the impact of DEFA1A3 in response to treatment have not been fully investigated. Therefore, we aimed to clarify the relationship between the number of DEFA1A3 copies and UC prednisolone treatment response. SUBJECTS AND METHODS Patients with UC who had attended our department and related facilities and had the number of DEFA1A3 copies measured were included between 2020 and 2022. The number of DEFA1A3 copies were measured using droplet digital PCR after DNA extraction from peripheral blood mononuclear cells. Mayo score was used to determine the response to prednisolone and severity of UC. ASUC was defined as presence of more than 6 bloody stools/d along with any one of the following: pulse rate> 90 bpm, temperature > 37.8 °C, hemoglobin < 10.5 g/dL, and/or CRP > 30mg/L. Clinical background and various parameters were extracted from medical record information. RESULTS The 47 ASUC patients were included in the study. The median DEFA1A3 copy number of the patients was 9, the median DEFA1A3 copy number in ASUC was higher than that in healthy subjects. The DEFA1A3 copy number was significantly higher in the non-remission group than in the remission group after treatment with prednisolone.There were no differences in other parameters such as CRP and WBC between the two groups. CONCLUSION DEFA1A3 copy number may be a predictive marker of prednisolone treatment response.