T cell clonal expansion linked to postop recurrence of Crohn's in smokers

Last Updated: 2019-03-11

By Reuters Staff

NEW YORK (Reuters Health) - Among smokers with Crohn's disease, increased T cell clonal expansion, especially in the CD8 compartment, is exaggerated and is associated with an increased rate of disease recurrence after ileocolonic resection, according to results from the REMIND Study Group.

Smoking behavior is one of the most consistent risk factors for postoperative endoscopic recurrence of Crohn's disease, but the underlying mechanism of this effect is not well understood.

Dr. Matthieu Allez from Hopital Saint Louis, in Paris, and colleagues previously described persistent clonal expansion of T cells in the inflamed mucosa of patients with Crohn's disease that might be associated with disease recurrence.

In the current study, they analyzed the T cell repertoire (TCR) in 57 patients (20 active smokers and 11 with at least one previous resection) with Crohn's disease who underwent ileocolonic resection for stricturing or penetrating complications of their disease.

Intestinal TCR showed clonal expansions that were highly variable between these patients, and the repertoire was often similar in inflamed and macroscopically non-inflamed areas of the surgical specimen.

The repertoire in these two locations could be very similar in some patients and very different in others. But if the repertoire was similar between the inflamed part and the proximal resection margin, it was also similar at the time of postoperative endoscopy six months later.

Active smokers had significantly more high-frequency clones (25.9%) than did non-smokers (17.9%), and the diversity of the TCR was reduced among smokers, the researchers report in Gut, online February 12.

The proportion of high-frequency clones at baseline was also significantly higher in patients with recurrence on postoperative endoscopy (23.2%) than in patients without recurrence (13.8%). Lower TCR diversity was also associated with higher rates of postoperative recurrence.

Most of the clonal expansions associated with postoperative disease recurrence were within the CD8 T cell lineage.

"Altogether, our data may help to define a subset of patients, characterized by a higher proportion of smokers and a T cell-driven pathogenesis," the researchers conclude. "This subset of patients could be potentially better treated with drugs targeting T cell driven pathways."

MSD France laboratories provided funding for the study and had various financial ties to several authors.

Dr. Allez did not respond to a request for comments.

SOURCE: https://bit.ly/2H1CaRH

Gut 2019.