Table 1.
Current molecular and clinical aspects involved in the pathogenesis of primary pouchitis
| Factors | Authors | Comments |
|---|---|---|
| Immune alterations | Segal et al., 2010. [18] | -Over-expression of molecules that participate in leukocyte activation and recognition |
| Kusunoki et al., 2006; Leal et al., 2011. [17,19] | -TLR2 and TLR4 expression upregulated | |
| Koltun et al., 2016; Barbara et al., 1994; Keighley et al., 1995; Goes et al., 2008. [129,20,21,26] | -Presence of pro-inflammatory cytokines in ileal pouches of UC patients, such as TNF-α, IL-1β, IL-6, IL-8, and interferon (IFN)-γ might explain higher rates of pouchitis in this group | |
| Desreumaux et al., 2000. [22] | -Decreased expression of IL-10 | |
| Neurath, et al., 2005. [28] | -Increased activation of the pro-inflammatory transcription factor STAT1 | |
| Herzig, et al., 2006. [31] | -Decreased levels of α and β defensins | |
| Kusunoki et al., 2020. [129] | -Increased IFN-γ mRNA expressions in patients who developed pouchitis | |
| Ponsioen et al., 2021. [130] | -Increased MAdCAM-1 expression in active inflammation in the pouch | |
| Genetic susceptibility | Peña et al., 2005. [35] | -Single-nucleotide polymorphisms (SNPs) involved in the susceptibility to pouchitis and its severity |
| Koltun et al., 2012. [34] | -Mutations in the nucleotide-binding and oligomerization domain (NOD) and TNFSF15 | |
| Peña et al., 2005. [35] | -Association of TLR9-1237C and CD14-120T alleles with the development of chronic pouchitis | |
| Autophagy/Apoptosis | Leal et al., 2018. [64] | -Modulation of macroautophagy markers leading to the mucosal inflammation with an increase of p62 in the ileal pouch |
| Heriot et al., 2006. [62] | -Differential expression of Beclin1 in the colon of UC patients | |
| Shen et al., 2012. [134] | -Increase in the deep crypt apoptosis in autoimmune pouchitis | |
| Góes, et al., 2008. [26] | -Increased expression of anti-apoptotic protein (phospho-BAD) in UC patients could explain higher rates of pouchitis in this group | |
| Mucosal ischemia-reperfusion | De Simone et al., 2001. [47] | -Increase of iNOS activity levels in the inflamed pouch compared with uninflamed control pouches |
| Blikslager et al., 2017. [113] | -TLR4-TRAF6 pathway and the effects of SOCS-1 may participate in the regulation of multi-organ damage caused by intestinal ischemia-reperfusion injury | |
| Environmental and clinical factors | Thirlby et al., 2000. [66] | -Greater occurrence of pouchitis in patients with extensive UC |
| van Heerden et al., 1990; Nozawa et al., 2019; Targan et al., 2007. [67,131,78] | -Pouchitis frequently occurred with a higher risk in patients with extraintestinal manifestations | |
| D’Hoore et al., 2008. [79] | -Younger age represents a higher risk of developing pouchitis | |
| Coates et al., 2018. [132] | -Cessation of smoking was associated with an increase in the development of pouchitis | |
| Pardi et al., 2013. [133] | -ANCA-positive patients present a higher risk of developing chronic pouchitis after IPAA | |
| Fukushima et al., 2012; Petrovska et al., 2010; Dotan et al., 2015. [89,93,94] | -The development of pouchitis was associated to a decrease in bacterial diversity in the microbiota of the ileal pouch, which would influence adequate functional performance |