Canine immunosuppressant-responsive enteropathy (IRE) is an intestinal 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 prognostic role of histopathological changes and Foxp3-positive T cell in the clinical response and relapse. CCECAI and CIBDAI scores have been assessed 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 morphologic features were evaluated: presence of crypt distension (CD), lacteal dilation (LD), mucosal fibrosis (MF) and intraepithelial lymphocytes (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 nonresponders (decreased CCECAI and CIBDAI <25% at T1 compared to T0). Relapse was evaluated as follows: from T3, if clinical scores was >3, differences (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 ≥2 were considered relapse. Associations between response or relapse and categorical 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 histological 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.
Foxp3 and Histopathological Lesions in Relation to Outcomes in Canine Immunosuppressant-Responsive Enteropathy (IRE): Prospective Analysis in 57 Dogs
Marco Pietra;
2019
Abstract
Canine immunosuppressant-responsive enteropathy (IRE) is an intestinal 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 prognostic role of histopathological changes and Foxp3-positive T cell in the clinical response and relapse. CCECAI and CIBDAI scores have been assessed 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 morphologic features were evaluated: presence of crypt distension (CD), lacteal dilation (LD), mucosal fibrosis (MF) and intraepithelial lymphocytes (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 nonresponders (decreased CCECAI and CIBDAI <25% at T1 compared to T0). Relapse was evaluated as follows: from T3, if clinical scores was >3, differences (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 ≥2 were considered relapse. Associations between response or relapse and categorical 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 histological 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
