Foxp3 and histopathological lesions in relation to outcomes in canine immunosuppressant-responsive enteropathy (Ire): prospective analysis in 57 dogs

Canine immunosuppressant-responsive enteropathy (IRE) is an intesti- nal idiopathic inflammation, in which diet and antibiotic trials failed and immunosuppressants are needed. The number of transcription factor forkhead box P3 (Foxp3)-Positive Regulatory T lymphocytes have been investigated in IBD dogs in association with mortality. The aim of the study was to evaluate the clinical significance and prognos- tic role of histopathological changes and Foxp3-positive T cell in the clinical response and relapse. CCECAI and CIBDAI scores have beenassessed at presentation (T0) and 1 (T1), 3 (T3), 6 (T6) and 12 months (T12) from diagnosis. Endoscopic biopsies histopathology and features were classified using WSAVA guidelines score. Moreover four mor- phologic features were evaluated: presence of crypt distension (CD), lacteal dilation (LD), mucosal fibrosis (MF) and intraepithelial lympho- cytes (IL). Immunohistochemistry for Foxp3 were performed in all cases. Dogs were classified as responders (decreased CCECAI and CIBDAI scores >25% at T1 compared to T0) and non-responders (decreased CCECAI and CIBDAI <25% at T1 compared to T0). Relapse was evaluated as follows: from T3, if clinical scores was >3, differ- ences (D) between CCECAI and CIBDAI at T3, T6 and T12 and the previous closest time point were calculated obtaining DCCECAI and CIBDAI T3-T1, T6-T3, T12-T6. A DCCECAI and CIBDAI 32 were con- sidered relapse. Associations between response or relapse and cate- gorical data were evaluated using Fisher's exact test and chi-square test. Fifty-seven dogs were prospectively enrolled. At T1, 9 and 8 dogs belongs to non-responders according to CIBDAI and CCECAI score, respectively. CIBDAI and CCECAI scores at T0 were not associated with T1 clinical response. Patients who relapsed were 5 (T3 and T6) and 4 dogs at T12, respectively. CIBDAI and CCECAI at T1, T3 and T6 were not associated with relapse. Dogs with histological WSAVA moderate had a higher response rate than severe dogs (P = 0.009, OR 6.5). However, histological scores were not associated with relapse rate. The 4 histological features were not associated neither with response nor with relapse rate. Presence of IL was associated with higher CIBDAI scores (P = 0.022). The percentage of Foxp3-positive cells was not associated with T0 CCECAI and CIBDAI or histological scores and morphologic features. The number of Foxp3-positive cells were not different between responders and non-responders and not related with relapse. Between the evaluated parameters, only histo- logical grade seems to predict clinical response at T1. Furthermore, none of the clinical or histological parameters, including Foxp3, seems to predict relapse in IRE dogs.