Isolation of Reovirus-Like Agents From Patients With Crohn's Disease

Whorwell, Peter J.; Beeken, Warren L.; Phillips, Charles A.; Little, P.K.; Roessner, Karen

doi:10.1016/s0140-6736(77)92714-3

Cited by 75 publications

(16 citation statements)

References 13 publications

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“…Also, the pathology of the disease, the multiple familial occurrences, and the multiple remote lesion sites all suggest an infectious process. Viruses (10,98,104,108,222,223,294,295,306) and L-form bacteria (19,139,261,295) have been incriminated most commonly, but in recent years these all have been discarded as candidate agents. To date, the etiology of Crohn's disease, being infectious, transmissible, or not, has eluded the scientific community.…”

mentioning

confidence: 99%

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

1989

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Crohn's disease is a chronic granulomatous ileocolitis, of unknown etiology, which generally affects the patient during the prime of life. Medical treatment is supportive at best, and patients afflicted with this disorder generally live with chronic pain, in and out of hospitals, throughout their lives. The disease bears the name of the investigator who convincingly distinguished this disease from intestinal tuberculosis in 1932. This distinction was not universally accepted, and the notion of a mycobacterial etiology has never been fully dismissed. Nevertheless, it was 46 years after the distinction of Crohn's disease and intestinal tuberculosis before research attempting to reassociate mycobacteria and Crohn's disease was published. Recently, there has been a surge of interest in the possible association of mycobacteria and Crohn's disease due largely to the isolation of genetically identical pathogenic Mycobacterium paratuberculosis from several patients with Crohn's disease in the United States, the Netherlands, Australia, and France. These pathogenic organisms have been isolated from only a few patients, and direct evidence for their involvement in the disease process is not clear; however, M. paratuberculosis is an obligate intracellular organism and strict pathogen, which strongly suggests some etiologic role. Immunologic evidence of a mycobacterial etiology, as assessed by humoral immune determinations, has been conflicting, but evaluation of the more relevant cellular immunity has not been performed. Data from histochemical searches for mycobacteria in Crohn's disease tissues have been equally conflicting, with acid-fast bacilli detected in 0 to 35% of patients. Animal model studies have demonstrated the pathogenic potential of isolates as well as elucidated the complexity of mycobacterial-intestinal interactions. Treatment of Crohn's disease patients with antimycobacterial agent has not been fully assessed, although case reports suggest efficacy. The similarities in the pathology, epidemiology, and chemotherapy of Crohn's disease and the mycobacterioses are discussed. The issue is fraught with controversy, and the data generated on the association of mycobacteria and Crohn's disease are in their infantile stages so that a general conclusion on the legitimacy of this association cannot be made. While no firm evidence clearly implicates mycobacteria as an etiologic agent of Crohn's disease, the notion is supported by suggestive and circumstantial evidence and a remarkable similarity of Crohn's disease to known mycobacterial diseases.

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confidence: 99%

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

1989

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“…Sera of neither Crohn disease nor control patients showed any staining when incubated with a normal lymph node from a nu/nu mouse or lymph nodes obtained from the mice injected with material from non-Crohn disease patients. In (1)(2)(3)(4)(5)(6)(7)(8)(9). After injection of homogenates of intestine or lymph node from Crohn disease patients into normal mice, a granulomatous reaction occurred at the injection site and in the intestine in 3-17 months.…”

Section: Nudementioning

confidence: 99%

“…Both local and systemic granulomata developed in normal and thymectomized CBA mice after repeated inocculation with Crohn tissue (4). Several laboratories described a virus (30-90 nm) in tissue culture monolayers that were inoculated with filtrates of Crohn tissue homogenates (5)(6)(7)(8)). An RNA virus was suggested because growth was not inhibited by 5-iodo-2'-deoxyuridine (6).…”

Section: Nudementioning

confidence: 99%

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

Das¹,

Valenzuela²,

Morecki³

1980

Proc. Natl. Acad. Sci. U.S.A.

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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.

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“…A virus with the physiochemical and growth characteristics, electron microscopical and antigenic properties of rotavirus has been found in some filtrates from resected intestine from adults with Crohn's disease (Whorwell et al, 1977a …”

Section: Rotavirus and Crohn's Diseasementioning

confidence: 99%

Rotavirus gastroenteritis.

Walker-Smith¹

1978

Archives of Disease in Childhood

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Isolation of Reovirus-Like Agents From Patients With Crohn's Disease

Cited by 75 publications

References 13 publications

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

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

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

Rotavirus gastroenteritis.

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