The Role of Inflammation in Crohn’s Disease Recurrence after Surgical Treatment

Table 1

Elements involved in CD recurrence.

Domain	Specific element	Putative mechanism of action	Level of evidence
Innate immune system	NOD2 gene; rs2066844 polymorphism	Improper activation of the immune response (pattern recognition receptor)	Low-moderate
Innate immune system	SMAD3	Drive fibrosis after initial surgical scarring	Low
Innate immune system	CARD8	IL-1 production, immune dysregulation	Low
Innate immune system	Matrix metalloproteinases	Initiation of inflammation/fibrosis	Low-moderate
Innate immune system	Macrophages	Bacterial trafficking to mesenteric nodes	Low
Innate immune system	Dendritic cells and basophils	Set up a potent and durable acquired immune response	Low
Adaptive immune system	Effector T-cells	Bring about most recurrent inflammation	Moderate-high
Adaptive immune system	Memory T-cells	Persist after resection in mesenteric lymph nodes (and blood to a lesser degree) and conserve immunological memory	Moderate-high
Adaptive immune system	B-cells	Produce anti-GM-CSF immunoglobulins; others	Low
Immune system as a whole	Dysbiosis	Increased bacterial trafficking; others	Low
Immune system as a whole	Increased mucosal IL-6; decreased mucosal IL-10; RNASET2 polymorphism	Increase mucosal inflammation	Low
Immune system as a whole	Inflammation at resection margins	Persistence of activated cells	Low
Immune system as a whole	Myenteric and submucosal plexitis	Unknown	Low
Immune system as a whole	Diet	Stimulate the immune system through poorly understood mechanisms	Low-moderate
Other risk factors	Smoking	Unknown; may increase mucosal T-cell hyperclonality	High
Other risk factors	Penetrating disease at index surgery, perianal disease, prior intestinal surgery extensive small bowel resection (>50 cm)	Unknown	High