Phenotypically aberrant and clonal T cell in the lung of patients with refractory coeliac disease

Background and objectives : coeliac disease (CD) is sometimes associated with extra-intestinal manifestations including cough, airway obstruction, pulmonary hemosiderosis and/or infiltrates. Tissue extra-intestinal aberrant lymphocytes have also been reported in skin lesions of type II refractory coeliac disease (RCD). We report here the first cases of RCD characteristic T cells and clones in the lung of patients with RCD. Methods : 5 patients (aged 51 ± 6 years) with confirmed RCD were referred to us for pulmonary symptoms (cough, dyspnea on exertion) and/or scanographic signs (mild infiltrates, micronodules). Mean time elapsed since RCD diagnosis was 22 months. Fiberoptic bronchoscopy was performed with bronchial biopsies (BB) and bronchoalveolar lavage (BAL) being analyzed for cytologic or histopathology, immunophenotyping and molecular status. Results : BAL exhibited a lymphocytic alveolitis in 3 cases (210±74.10 3 cells/mL, 27±4% lymphocytes, CD4/CD8 ratio: 3.5±1, mean±SEM). Aberrant CD3-/CD4-/CD8- alveolar T lymphocytes were found in all cases. Three of them exhibited clonal TCRγ rearrangements. BB showed no inflammatory infiltrates but T cell clones identical to those present in the intestinal epithelium in 3/5 cases. Two of 5 patients died of intestinal or skin lymphoma, none of pulmonary complication so far (mean follow up: 3.4 years). Conclusion : These data highlight the importance of a systematic pulmonary work-up in patients with RCD, at high risk of developing aggressive lymphomas. Ongoing studies are assessing the prevalence of such pulmonary abnormalities in RCD subjects and will tell us about their specific impact on the disease outcome.