Immunological abnormalities associated with hereditary haemorrhagic telangiectasia

Objective Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder related to mutations in one of the coreceptors to the transforming growth factor- 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. Results 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 cellsL(-1) vs. 832 cellsL(-1), P<0.001), CD8 (295 cellsL(-1) vs. 501 cellsL(-1), P<0.0001) and natural killer (NK) cells (169 cellsL(-1) vs. 221 cellsL(-1), P<0.01), associated with increased levels of immunoglobulins G and A. This lymphopenia mainly concerned naive 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. Conclusions 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.