P014 Mucosal lymphocyte subsets in ulcerative colitis at diagnosis and during follow-up
Smids C.*1, Horjus Talabur Horje C.1, Groenen M.1, van Koolwijk E.2, Wahab P.1, van Lochem E.2
1Rijnstate Hospital, IBD Centre, Gastroenterology and Hepatology, Arnhem, Netherlands 2Rijnstate Hospital, Microbiology and Immunology, Arnhem, Netherlands
The initial immunologic processes that occur in the inflamed mucosa of patients with Ulcerative Colitis (UC) remain largely unclear. We aimed to investigate different mucosal lymphocyte subsets in UC patients at diagnosis and during follow-up to study the changes that might occur in different phases of disease activity (remission/exacerbation).
A total of 35 newly diagnosed untreated adult UC patients and seven healthy controls (HC) were prospectively included. Colonic biopsy specimens of the inflamed areas were collected at diagnosis and, from the same colon segment, during follow-up. Flow cytometry was used to analyse lymphocyte subsets in the colonic biopsy specimen as defined in Table 1.
At diagnosis UC patients displayed higher percentages of CD4+, TCM and lower percentages of CD8+, TEM and mucosal T cells compared to HC (Table 1 and Figure 1).
Compared to diagnosis, a statistical significant increase of mucosal T cells and TEM cells was found in patients colon during remission at follow up (median time to follow-up 20 months, IQR 16–30). No differences compared to baseline percentages were observed in patients with an exacerbation at follow-up (26 months, 19–54, p=0.238) (Table 1 and Figure 1).
Lymphocyte subsets, median % (interquartile range) Healthy controls Ulcerative colitis – baseline Follow-up – remission Follow-up – exacerbation p-value between follow-up groups (n=7) (n=35) (n=8) (n=11) T cells (CD3+) 58 (40–61) 57 (48–69) 54 (48–78) 48 (39–62) 0.247 CD4+ T cells (CD3+CD4+) 40 (33–57) 74 (66–83)a 54 (40–70) 80 (75–87)a 0.001 CD8+ T cells (CD3+CD4+) 52 (33–55) 21 (16–29)a 37 (24–54) 13 (10–22)a 0.002 Mucosal T cells (CD3+CD103+) 40 (32–60) 12 (6–18)a 36 (14–57)b 7 (2–15)a 0.004 Regulatory T cells (CD3+CD4+CD25highFoxP3+) 8 (3–12) 10 (8–14) 7 (3–10) 11 (8–16) 0.055 Naive T cells (TN, CD3+CD27+CD45RA+) 13 (10–24) 21 (12–30) 8 (5–15) 18 (14–34) 0.013 T effector memory cells re-expressing CD45RA (TEMRA, CD3+CD27–CD45RA+) 2 (1–6) 4 (2–8) 4 (2–7) 3 (3–4) 0.165 Central memory T cells (TCM, CD3+CD27+CD45RA–) 30 (21–36) 50 (39–58)a 25 (10–44) 55 (50–77)a 0.005 Effector memory T cells (TEM, CD3+CD27–CD45RA–) 52 (39–58) 21 (12–29)a 56 (23–80)b 11 (5–21)a 0.003
UC patients in remission at follow-up had comparable lymphocyte subsets to HC (P values all >0.05), while patients with an exacerbation at follow-up had comparable findings to baseline and the same statistical significant differences in lymphocyte subsets were observed compared to HC.
Mucosal inflammation was associated with increased percentages of CD4+ T cells and TCM cells and decreased percentages of (mucosal) CD103+ T cells, CD8+ T cells and TEM cells. A trend towards normalization of the colonic T cell profile, with increase of CD103+ and TEM cells, is seen during remission; suggesting a positive role for these mucosal T cell subpopulations. These observations could question the efficacy of anti-CD103 treatment in UC patients. More research is needed to elucidate the pathological and regulatory effects of the different lymphocyte subsets, as well as their potential predictive role for response to therapy.