BACKGROUND AND OBJECTIVE: Elevated/activated myeloid leucocytes, like the CD14(+)CD16(+) monocytes are sources of TNF-α, and therefore, selective depletion of these cells by granulocyte/monocyte (GM) adsorption (GMA) should promote remission or enhance drug efficacy. However, studies in ulcerative colitis (UC) reported contrasting efficacy, from an 85% to statistically insignificant level. We investigated patients' demography in responders and non-responders. METHODS: In 120 UC patients, 61 steroid naive and 59 steroid dependent, we looked for entry clinical or endoscopic features to identify responders (or non-responders) to GMA. Patients received up to an 11 Adacolumn GMA sessions over 12 weeks. Patients were clinically and endoscopically evaluated, allowing each patient to serve as her/his own control. Immunohistochemistry on colonic biopsies was to reveal the impact of GMA on leucocyte infiltration of the mucosa. RESULTS: Entry average clinical activity index (CAI) was 12.6, 10-16. An 80 of 120 patients responded (CAI≤4); 45 steroid naïve (73.8%) and 35 steroid dependent (59.3%). Over 900 biopsies were processed. Infiltrating leucocytes were overwhelmingly polymorphonuclear and macrophages around and within crypt abscesses. There was a marked reduction of infiltrating leucocytes in responders. Most non-responders had extensive colonic lesions with virtually no mucosal tissue left at the lesions. CONCLUSIONS: Steroid naïve patients with short duration of UC were the best responders, while patients with deep colonic lesions and extensive loss of the mucosal tissue were non-responders.
BACKGROUND AND OBJECTIVE: Elevated/activated myeloid leucocytes, like the CD14(+)CD16(+) monocytes are sources of TNF-α, and therefore, selective depletion of these cells by granulocyte/monocyte (GM) adsorption (GMA) should promote remission or enhance drug efficacy. However, studies in ulcerative colitis (UC) reported contrasting efficacy, from an 85% to statistically insignificant level. We investigated patients' demography in responders and non-responders. METHODS: In 120 UC patients, 61 steroid naive and 59 steroid dependent, we looked for entry clinical or endoscopic features to identify responders (or non-responders) to GMA. Patients received up to an 11 Adacolumn GMA sessions over 12 weeks. Patients were clinically and endoscopically evaluated, allowing each patient to serve as her/his own control. Immunohistochemistry on colonic biopsies was to reveal the impact of GMA on leucocyte infiltration of the mucosa. RESULTS: Entry average clinical activity index (CAI) was 12.6, 10-16. An 80 of 120 patients responded (CAI≤4); 45 steroid naïve (73.8%) and 35 steroid dependent (59.3%). Over 900 biopsies were processed. Infiltrating leucocytes were overwhelmingly polymorphonuclear and macrophages around and within crypt abscesses. There was a marked reduction of infiltrating leucocytes in responders. Most non-responders had extensive colonic lesions with virtually no mucosal tissue left at the lesions. CONCLUSIONS:Steroid naïve patients with short duration of UC were the best responders, while patients with deep colonic lesions and extensive loss of the mucosal tissue were non-responders.
Authors: H Hanai; Y Takeda; M Eberhardson; R Gruber; A R Saniabadi; O Winqvist; R Lofberg Journal: Clin Exp Immunol Date: 2010-11-16 Impact factor: 4.330