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Evidence of persistent measles virus infection in Crohn's disease
A J Wakefield1, R M Pittilo, R Sim
1Inflammatory Bowel Disease Study Group, Royal Free Hospital School of Medicine, London, United Kingdom.
Abstract:
Transmission electron microscopy was used to examine the microvasculature of perfusion-fixed tissues from Crohn's disease and control patients. Paramyxovirus-like particles, and inclusions consisting of condensations of nucleocapsid, in giant cells and endothelium at foci of vascular injury were identified in all 9 Crohn's disease patients. Tissues from patients with Crohn's disease were also examined by either in situ hybridisation (n = 10) or immunohistochemistry (n = 15), and compared to inflammatory and noninflammatory controls (n = 22). Hybridisation for measles virus N-protein genomic RNA was positive in all cases of Crohn's disease localising to foci of granulomatous vasculitis and lymphoid follicles. Positive immunohistochemical staining for measles virus nucleocapsid protein was positive in 13 of 15 patients with Crohn's disease, localising to foci of granulomatous inflammation. Hybridisation for measles virus RNA was positive in a minority of control intestinal tissues; viral inclusions were not seen ultrastructurally. Immunostaining was negative in control cases of intestinal tuberculosis. These observations suggest that measles virus is capable of causing persistent infection of the intestine and that Crohn's disease may be caused by a granulomatous vasculitis in response to this virus.
Insights
Measles virus particles and RNA were found in Crohn
Area of Science:
- Gastroenterology
- Virology
- Pathology
Background:
- Crohn's disease is a chronic inflammatory bowel condition of unknown etiology.
- Previous research has suggested a potential role for viral infections in Crohn's disease pathogenesis.
- Microvascular injury is a characteristic feature observed in Crohn's disease tissues.
Purpose of the Study:
- To investigate the presence of paramyxovirus-like particles and measles virus in intestinal tissues of Crohn's disease patients.
- To determine if measles virus infection is associated with the vascular changes seen in Crohn's disease.
Main Methods:
- Transmission electron microscopy (TEM) was used to examine microvasculature in Crohn's disease and control tissues.
- In situ hybridization (ISH) and immunohistochemistry (IHC) were employed to detect measles virus N-protein genomic RNA and nucleocapsid protein, respectively.
- Tissues from Crohn's disease patients (n=9-15) and controls (n=22) were analyzed.
Main Results:
- Paramyxovirus-like particles and nucleocapsid inclusions were identified in endothelial cells and giant cells in all Crohn's disease patients examined by TEM.
- Measles virus N-protein genomic RNA was detected by ISH in all Crohn's disease cases, localized to areas of granulomatous vasculitis.
- Measles virus nucleocapsid protein was positive by IHC in 13 of 15 Crohn's disease patients, found in granulomatous inflammation foci. Viral markers were largely absent in controls.
Conclusions:
- These findings suggest that measles virus can establish persistent intestinal infections.
- The study proposes that Crohn's disease may result from a granulomatous vasculitis triggered by measles virus infection.