Immunological abnormalities associated with hereditary haemorrhagic telangiectasia
Article first published online: 4 JUL 2013
© 2013 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 274, Issue 4, pages 351–362, October 2013
How to Cite
Hôpital Saint Eloi, Montpellier; Hôpital E Herriot, Lyon; Hôpital E Herriot, Lyon; Hôpital La Colombiere, Montpellier; Centre National de Référence pour la Maladie de Rendu-Osler, Hôpital Louis Pradel, Bron, France. Immunological abnormalities associated with hereditary haemorrhagic telangiectasia. J Intern Med 2013; 274: 351–362., , , ,
- Issue published online: 10 SEP 2013
- Article first published online: 4 JUL 2013
- Accepted manuscript online: 14 JUN 2013 09:12PM EST
- Manuscript Accepted: 2 MAY 2013
- Association Française Maladie de Rendu-Osler-Weber (AMRO France-HHT)
- hereditary hemorrhagic telangiectasia;
- immunologic deficiency syndromes;
- immunoglobulins M;
- T lymphocytopenia
Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder related to mutations in one of the coreceptors to the transforming growth factor-β superfamily (ALK1 or endoglin). Besides the obvious vascular symptoms (epistaxis and arteriovenous malformations), patients have an unexplained high risk of severe bacterial infections. The aim of the study was to assess the main immunological functions of patients with HHT using the standard biological tests for primary immunodeficiencies.
Design, setting and subjects
A prospective single-centre study of 42 consecutive adult patients with an established diagnosis of HHT was conducted at the National French HHT Reference Center (Lyon). Lymphocyte subpopulations and proliferation capacity, immunoglobulin levels and neutrophil and monocyte phagocytosis, oxidative burst and chemotaxis were assessed.
Innate immunity was not altered in patients with HHT. With regard to adaptive immunity, significant changes were seen in immunological parameters: primarily, a lymphopenia in patients with HHT compared with healthy control subjects affecting mean CD4 (642 cells μL−1 vs. 832 cells μL−1, P < 0.001), CD8 (295 cells μL−1 vs. 501 cells μL−1, P < 0.0001) and natural killer (NK) cells (169 cells μL−1 vs. 221 cells μL−1, P < 0.01), associated with increased levels of immunoglobulins G and A. This lymphopenia mainly concerned naïve T cells. Proliferation capacities of lymphocytes were normal. Lymphopenic patients had a higher frequency of iron supplementation but no increase in infection rate. Lower levels of immunoglobulin M and a higher rate of pulmonary arteriovenous malformations were found amongst patients with a history of severe infection.
Patients with HHT exhibit immunological abnormalities including T CD4, T CD8 and NK cell lymphopenia and increased levels of immunoglobulins G and A. The observed low level of immunoglobulin M requires further investigation to determine whether it is a specific risk factor for infection in HHT.