title: Immunological abnormalities associated with hereditary haemorrhagic telangiectasia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 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.
  
  
  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.
authors.affiliation: CHU de Montpellier, Service de Médecine Interne A, Hôpital Saint Eloi, Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Guilhem
authors.forename: C
authors.initials: C
authors.lastname: Malcus
authors.forename: B
authors.initials: B
authors.lastname: Clarivet
authors.forename: H
authors.initials: H
authors.lastname: Plauchu
authors.forename: S
authors.initials: S
authors.lastname: Dupuis-Girod
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D006942:Hypergammaglobulinemia / Q000209:etiology* / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008231:Lymphopenia / Q000209:etiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000150:complications* / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G
keywords: T lymphocytopenia; hereditary hemorrhagic telangiectasia; immunoglobulins M; immunologic deficiency syndromes