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

Abstract

To study the putative agent(s) related to Crohn disease, mesenteric lymph node homogenates from 4 patients with active Crohn disease [were injected i.p.] into 10-wk-old athymic (nu/nu) mice. Control mice (nu/nu) were injected with homogenates of mesenteric lymph nodes from 2 patients with ulcerative colitis and 4 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; 32 mice received homogenates or filtrates from lymph nodes of control patients. Four mice from the group injected with Crohn disease homogenates from 4 different patients developed generalized lymphadenopathy due to lymphoma 10-28 wk after the 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 i.p. into a 2nd group of nu/nu mice, which also developed lymphoma within 8 wk of injection. Two lymphomas were cultured in vitro and B [bone marrow-derived] cell surface markers were identified. Indirect immunofluorescence studies in 2 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. Apparently a transmissible factor present in Crohn disease lymph nodes produces lymphoma in nu/nu mice. Sera of Crohn disease patients contain an antibody that recognizes an antigen(s) in the murine lymphoma.