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Keywords:

  • adsorptive granulocyte/monocyte apheresis;
  • CD4+CD25high+;
  • FoxP3+;
  • Treg;
  • UC

Summary

Regulatory T cells (Treg) have an essential role in maintaining immune tolerance in the gut. The functional CD4+ Treg express the transcription factor forkhead box protein 3 (FoxP3) or a CD25high in humans. Further, depletion of elevated granulocytes/monocytes by extracorporeal adsorption (GMA) induces immunomodulation in patients with ulcerative colitis (UC). We investigated the impact of GMA on Treg. Thirty-one UC patients, clinical activity index (CAI) 12·1 ± 2·97, refractory to conventional medications including intravenous corticosteroid and 13 healthy controls (HC), were included. Patients received five GMA sessions over 5 weeks. Biopsies from the rectal mucosa and blood samples at baseline and post-GMA were immunostained with anti-CD4/FoxP3 and anti-CD4/CD25 antibodies for immunohistochemistry and flow cytometry. Following GMA, 22 of 31 patients achieved remission (CAI ≤ 4, P < 0·01) and their endoscopic activity index decreased from 10·6 ± 2·32 to 4·75 ± 1·48 (P = 0·003). The circulating CD4+CD25high+ Treg level was low and increased markedly in responders (P < 0·02). In the nine non-responders, the baseline CD4+CD25high+ Treg level was about 50% of the level in the responders (P < 0·03) or in the HC (P < 0·01), and all nine had to undergo colectomy. Conversely, the number of CD4+/FoxP3+ mucosal Treg in GMA responders decreased significantly after the fifth GMA session compared with the baseline level (P < 0·05). It is believed that the CD4+ Treg has an essential role in the control of immune pathology in UC patients and a net influx of these cells from the circulation into the mucosa may proceed to suppress inflammation. GMA can impact the circulating as well as the mucosal levels of Treg.