ORIGINAL ARTICLE

Potential viral pathogenic mechanism for new variant inflammatory bowel disease

V Uhlmann^1,*, C M Martin^2,*, O Sheils², L Pilkington¹, I Silva¹, A Killalea¹, S B Murch³, J Walker-Smith⁴, M Thomson⁴, A J Wakefield⁴, J J O'Leary¹

¹ Department of Pathology, Coombe Women's Hospital, Dublin 8, Ireland
² Department of Histopathology, Trinity College, Dublin, Ireland,
³ Department of Paediatric Gastroenterology, the Royal Free Hospital, London, UK
⁴ Department of Medicine, The Royal Free Hospital and University College Medical School, London, UK

Correspondence to:
Correspondence to:
Professor J J O'Leary, Department of Pathology, Coombe Women's Hospital, Dublin 8, Ireland;
joleary{at}coombe.ie

Aims: A new form of inflammatory bowel disease (ileocolonic lymphonodular hyperplasia) has been described in a cohort of children with developmental disorder. This study investigates the presence of persistent measles virus in the intestinal tissue of these patients (new variant inflammatory bowel disease) and a series of controls by molecular analysis.

Methods: Formalin fixed, paraffin wax embedded and fresh frozen biopsies from the terminal ileum were examined from affected children and histological normal controls. The measles virus Fusion (F) and Haemagglutinin (H) genes were detected by TaqMan reverse transcription polymerase chain reaction (RT-PCR) and the Nucleocapsid (N) gene by RT in situ PCR. Localisation of the mRNA signal was performed using a specific follicular dendritic cell antibody.

Results: Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia. The copy number of measles virus ranged from one to 300 000 copies/ng total RNA.

Conclusions: The data confirm an association between the presence of measles virus and gut pathology in children with developmental disorder.

Keywords: inflammatory bowel disease; measles; developmental disorder

Abbreviations: AP, alkaline phosphatase; BCIP, bromochloroindoylphosphate; DIG, digoxigenin; F, fusion; H, haemagglutinin; IL, interleukin; LNH, lymphonodular hyperplasia; MV, measles virus; N, nucleocapsid; NBT, nitrobluetetrazolium; PCR, polymerase chain reaction; RT, reverse transcription; SSC, saline sodium citrate; SSPE, subacute sclerosing panencephalitis; Th1, T helper cell type 1

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