Crohn disease lymph node homogenates produce murine lymphoma in athymic mice.

Abstract

To study the putative agent(s) related to Crohn disease, we intraperitoneally in injected mesenteric lymph node homogenates from four patients with active Crohn disease into 10-week-old athymic (nu/nu) mice. Control mice (nu/nu) were injected with homogenates of mesenteric lymph nodes from two patients with ulcerative colitis and four patients undergoing elective cholecystectomy, and with a homogenate of a cervical lymph node containing sarcoid granuloma. Thirty-four mice received filtered or unfiltered homogenates from Crohn disease lymph nodes. Thirty-two mice received homogenates or filtrates from lymph nodes of control patients. Four mice from the group injected with Crohn disease homogenates from four different patients developed generalized lymphadenopathy due to lymphoma 10-28 weeks after th injection. Two additional mice developed lymphadenopathy due to plasma cell hyperplasia. None of the control mice developed lymphomas or lymphadenopathy. Two lymphomas were homogenized, filtered, and injected intraperitoneally into a second group of nu/nu mice, which also developed lymphoma within 8 weeks of injection. Two lymphomas were cultured in vitro and B cell sur?ACE MARKERS WERE IDENTIFIED. Indirect immunofluorescence studies in two lymphomas showed cytoplasmic staining of lymphoma cells with sera from 10 patients with active Crohn disease but not with sera from 13 control subjects, including 6 with ulcerative colitis and 7 with other gastrointestinal disorders. These results suggest that a transmissible factor present in Crohn disease lymph nodes produces lymphoma in nu/nu mice. Furthermore, sera of Crohn disease patients contain an antibody that recognizes an "antigen(s)" in the murine lymphoma.

Increased incidence of non-Hodgkin's lymphoma in inflammatory bowel disease patients on immunosuppressive therapy but overall risk is low

“…Of note, most non-transplant studies have demonstrated that immunosuppression related NHL does not show the same predilection for the brain as those in transplant recipients. Furthermore, in the setting of immunosuppression, it is interesting to note that Crohn's tissue homogenates have been reported to induce B cell lymphomas in athymic mice suggesting, at least in experimental animals, a link between Crohn's disease, immunosuppression, and malignant lymphoma 41. In addition, three of our four cases were large cell diffuse B cell lymphomas, which are by far the commonest type of immunosuppression induced lymphoma described 42…”

Mycobacterium paratuberculosis Monoassociated Nude Mice as a Paratuberculosis Model

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], and 314 mice euthanatized at 5 months (Nos. 2 1-23) appeared healthy.…”

Crohn's disease and the mycobacterioses: a review and comparison of two disease entities

“…In a multicenter study in which various investigators exchanged material, a transmissible histologic abnormality could not be reproduced (272). In recent years, Das et al (69) have described the production of lymphomas or plasma cell hyperplasia in nude mice by the injection of Crohn's disease tissue. Also, these authors claim that sera from Crohn's disease patients react with certain cells or cell types in these murine lymphomas as demonstrated by the fluorescent-antibody technique (13,301,310).…”