Antimouse CD52 monoclonal antibody inhibits established spontaneous colitis in IL-10-deficient mice.

CD52, a glycoprotein, attaches to the mature lymphocytes cell membrane by a glycosylphosphatidylinositol anchor, which is expressed by B and T lymphocytes at high levels and by monocytes, macrophages, and eosinophils at lower levels. Alemtuzumab (Campath-1H) is a humanized monoclonal antibody recognizing the CD52 antigen and is capable of selectively killing CD52-expressing cells. Alemtuzumab has been used clinically in the treatment of autoimmune diseases such as rheumatoid arthritis (RS) and multiple sclerosis (MS). Although the exact pathogenesis of Crohn’s disease (CD) is not fully understood, a defect of lamina propria (LP) T-cell apoptosis is suspected, resulting in an inappropriate cell activation and proliferation, which is considered to be a crucial mechanism involved in an exaggerated immune response and release of proinflammatory cytokines. Interleukin-10-deficient (IL-10 / ) mice develop spontaneous inflammation of the colon, a process that is T-cell-dependent, and characterized by both pathologic T-helper type 1 (Th1) and Th17 immune response observed in CD. Recently, Qu et al reported that 20 lg of antimouse CD52 monoclonal antibody (mAb) could reduce the number of intestinal intraepithelial lymphocytes (IELs) by 50% in mice. We recently performed a study to evaluate the therapeutic effect of antimouse CD52 mAb on spontaneous colitis in IL-10 / mice. IL-10 / mice (Jackson Laboratory, Bar Harbor, ME) 9 months old were treated with antimouse CD52 mAb (20 lg diluted with phosphatebuffered saline [PBS], intraperitoneal injection; MBL, Naka-ku Nagoya, Japan). One week later, the drug was administrated again with the same dose. One week after the final drug administration the disease activity index (DAI), serum SAA protein concentrations, macroscopic features, and pathologic findings of colon were evaluated. CD52 mAb-treated mice showed lower mean DAI values when compared to PBS-treated IL-10 / mice (2.67 6 0.52 versus 3.83 6 0.75, P 1⁄4 0.011). The SAA protein, an acute phase protein showed the closet correlation with CDAI and histological activity, which can be a useful marker of inflammation, were significantly lower in CD52 mAb-treated mice than those in PBS-treated IL-10 / mice (169.07 6 50.5 lg/mL versus 296.27 6 53.2 lg/mL, P 1⁄4 0.02). It was reported that colonic inflammation has been correlated with decreased colon length in rodent models of colitis, and the length of colon is widely accepted as a reliable inflammation index of colitis. Our results indicated that CD52 mAb-treated mice had significantly longer colons than PBS-treated IL-10 / mice (8.97 6 0.89cm versus 8.01 6 0.34 cm, P 1⁄4 0.034); additionally, treatment with CD52 mAb dramatically decreased the colon weights of IL-10 / mice (49.13 6 4.56 mg/cm versus 57.02 6 6.88 mg/cm, P 1⁄4 0.041). Thus, CD52 mAb had therapeutic activity in older IL-10-deficient mice with established colitis. CD52 mAb-treated IL-10 / mice showed significantly less infiltration of inflammatory cells (Fig. 1A). In the IL-10 / model of chronic IBD, the inflammatory infiltrate in the colon contains large numbers of lymphocytes, while administration of CD52 mAb improved the infiltrate of lymphocytes, restoring the histological appearance of the mucosa and