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Detection and comparative analysis of persistent measles virus infection in Crohn's disease by immunogold electron
1Inflammatory Bowel Disease Study Group, School of Life Sciences, Kingston University, Kingston-on-Thames, Surrey, United Kingdom.
Aims:
To determine the specificity of persistent measles virus infection in intestinal samples from Crohn's disease patients using quantitative immunogold electron microscopy. To compare the results with samples from ulcerative colitis, a granulomatous inflammatory control (tuberculous lymphadenitis), and a positive control.
Methods:
Formalin fixed, paraffin embedded intestinal tissue from patients with Crohn's disease was reprocessed and stained with antimeasles nucleocaspid protein primary antibody followed by 10 nm gold conjugated secondary antibody. Tissue samples were taken from granulomatous and non-granulomatous areas of the intestine. Intestinal samples from patients with ulcerative colitis, tuberculous lymphadenitis, or acute mesenteric ischaemia were similarly processed. Brain tissue from a patient with subacute sclerosing panencephalitis (SSPE) was used as the positive control. Duplicate sections of all tissues were processed without the primary antibody. Stained specimens were examined by electron microscopy.
Results:
In Crohn's disease patients, 8/9 foci of granulomatous inflammation and 0/4 foci of non-specific inflammation were positive for measles virus. Of controls, 0/5 non-inflamed intestinal tissues, 1/8 tuberculous tissues, 1/5 ulcerative colitis tissues, and 1/1 SSPE tissues were positive. Gold grain counts per nuclear field-of-view in both Crohn's disease granulomas (43.29) and SSPE (36.94) were significantly higher than in tissues from patients with ulcerative colitis (13.52) or tuberculous lymphadenitis (15.875), and nongranulomatous areas of Crohn's disease (4.89) (p < 0.001, p < 0.001, p = 0.0006, respectively), with no significant difference between Crohn's disease and SSPE (p > 0.1). In both SSPE and Crohn's disease staining was confined to a small population of cells exhibiting characteristic cytopathology.
Conclusion:
These data support a role for measles virus in the aetiology of Crohn's disease.
Insights
Measles virus was detected in intestinal granulomas of Crohn's disease patients. These findings suggest a potential role for measles virus in the development of Crohn's disease, supporting further research into viral triggers.
Area of Science:
- Gastroenterology
- Virology
- Immunology
Background:
- Crohn's disease (CD) is a chronic inflammatory bowel disease of unknown etiology.
- Persistent viral infections are implicated in the pathogenesis of some chronic inflammatory conditions.
Purpose of the Study:
- To investigate the presence and specificity of persistent measles virus (MeV) infection in intestinal tissues of Crohn's disease patients.
- To compare MeV detection in CD with other inflammatory conditions and controls.
Main Methods:
- Quantitative immunogold electron microscopy was used to detect MeV nucleocapsid protein in intestinal biopsies.
- Tissues from Crohn's disease, ulcerative colitis, tuberculous lymphadenitis, and healthy controls were analyzed.
- Subacute sclerosing panencephalitis (SSPE) brain tissue served as a positive control.
Main Results:
- Measles virus was identified in 8/9 granulomatous inflammation foci in Crohn's disease patients.
- MeV detection was significantly higher in Crohn's disease granulomas compared to ulcerative colitis and tuberculous lymphadenitis tissues.
- Gold grain counts in CD granulomas were comparable to the positive control (SSPE), indicating specific viral presence.
Conclusions:
- The findings provide evidence supporting a role for measles virus in the etiology of Crohn's disease.
- Further investigation into MeV as a potential trigger for CD pathogenesis is warranted.