P. R. Pannu1, G. S. Yochum2, R. A. Hodin1, W. A. Koltun2, N. Saeidi1 1Massachusetts General Hospital, Surgery, Boston, MA, USA 2Penn State Hershey Medical Center, York, PA, USA
Introduction: Inflammatory bowel disease (IBD), encompassing Crohn’s Disease and Ulcerative Colitis, has been predominantly characterized as affecting Caucasian populations. However, through advancements in research and healthcare access, it is now clear that IBD is increasingly affecting all people, including African Americans. Racial disparities in disease characteristics, severity, and progression have been suggested between African American and Caucasian patients with IBD. However, the potential role of underlying biological factors leading to these racial differences is yet to be unraveled.
Methods: Resected colon samples from 15 African American and 15 Caucasian patients with IBD (16 Crohn’s disease; 14 Ulcerative Colitis) were evaluated. Age-, sex- and duration of disease-matched samples were compared for: 1) Histological damage using Hematoxylin and Eosin (H&E) staining, 2) Extent of fibrosis with Masson’s Trichrome and Collagen staining, and 3) Colon immunophenotyping and cytokine profiling with flow cytometry. Furthermore, we utilized a chronic colitis model (3 cycles of 2.5% DSS for 1 week followed by 2 weeks of water in each cycle) and compared outcomes in pigmented vs non-pigmented C57BL/6J mice.
Results: African American patients showed evidence of higher histological damage when compared with Caucasian patients, seen as more prominent lamina propria immune cell infiltration, crypt architectural distortion and epithelial erosions and ulceration on H&E staining. Additionally, extent of collagen deposition on Masson’s Trichrome (12.5% vs 5.1%, p<0.01) and Collagen I (16.2% vs 2.7%, p<0.01) was significantly higher in African Americans than Caucasians. Furthermore, colon profiling revealed higher levels of pro-inflammatory cytokines like TNF-α and IFN-γ in African American patients compared to Caucasians. Interestingly, pigmented mice developed more severe disease when compared with non-pigmented mice, observed as shorter colon lengths and slower recovery from body weight loss following induction of chronic colitis (p<0.01). Histological analysis of colon tissues from pigmented mice demonstarted more prominent damage characterized by severe disruption of tissue architecture, increased immune cell infiltration and epithelial denudation compared to non-pigmented mice. Similar to human findings, pigmented mice showed higher levels of pro-inflammatory cytokines TNF-α and IFN-γ in colon when compared with non-pigmented mice.
Conclusion: Our findings demonstrate evidence of more severe disease in African Americans with IBD when compared with Caucasian patients. Furthermore, results from the chronic colitis murine model validate its role in investigating the precise underlying mechanisms of IBD, including differences based on pigmentation.