title: Clinical and laboratory correlates of lung disease and cancer in adults with idiopathic hypogammaglobulinaemia.
abstract: Idiopathic hypogammaglobulinaemia, including common variable immune deficiency (CVID), has a heterogeneous clinical phenotype. This study used data from the national UK Primary Immune Deficiency (UKPID) registry to examine factors associated with adverse outcomes, particularly lung damage and malignancy. A total of 801 adults labelled with idiopathic hypogammaglobulinaemia and CVID aged 18-96 years from 10 UK cities were recruited using the UKPID registry database. Clinical and laboratory data (leucocyte numbers and serum immunoglobulin concentrations) were collated and analysed using uni- and multivariate statistics. Low serum immunoglobulin (Ig)G pre-immunoglobulin replacement therapy was the key factor associated with lower respiratory tract infections (LRTI) and history of LRTI was the main factor associated with bronchiectasis. History of overt LRTI was also associated with a significantly shorter delay in diagnosis and commencing immunoglobulin replacement therapy [5 (range 1-13 years) versus 9 (range 2-24) years]. Patients with bronchiectasis started immunoglobulin replacement therapy significantly later than those without this complication [7 (range 2-22) years versus 5 (range 1-13) years]. Patients with a history of LRTI had higher serum IgG concentrations on therapy and were twice as likely to be on prophylactic antibiotics. Ensuring prompt commencement of immunoglobulin therapy in patients with idiopathic hypogammaglobulinaemia is likely to help prevent LRTI and subsequent bronchiectasis. Cancer was the only factor associated with mortality. Overt cancer, both haematological and non-haematological, was associated with significantly lower absolute CD8(+) T cell but not natural killer (NK) cell numbers, raising the question as to what extent immune senescence, particularly of CD8(+) T cells, might contribute to the increased risk of cancers as individuals age.
authors.affiliation: Paediatric Allergy and Immunology, University of Manchester, Manchester.
authors.forename: J
authors.initials: J
authors.lastname: Brent
authors.affiliation: UK-PIN UKPID Registry Team, London and Manchester.|Immunology, Royal Free Hospital, London.
authors.forename: D
authors.initials: D
authors.lastname: Guzman
authors.affiliation: Paediatric Allergy and Immunology, University of Manchester, Manchester.|UK-PIN UKPID Registry Team, London and Manchester.
authors.forename: C
authors.initials: C
authors.lastname: Bangs
authors.affiliation: UK-PIN UKPID Registry Team, London and Manchester.
authors.forename: B
authors.initials: B
authors.lastname: Grimbacher
authors.affiliation: Immunology, St Bartholomew's Hospital, London.
authors.forename: C
authors.initials: C
authors.lastname: Fayolle
authors.affiliation: West Midlands Immunodeficiency Centre, Birmingham Heartlands Hospital, Birmingham.
authors.forename: A
authors.initials: A
authors.lastname: Huissoon
authors.affiliation: Immunology, Derriford Hospital, Plymouth.
authors.forename: C
authors.initials: C
authors.lastname: Bethune
authors.affiliation: Immunology, NHS Greater Glasgow and Clyde, Glasgow.
authors.forename: M
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Immunology, John Radcliffe Hospital, Oxford.
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Immunology, University Hospital of Wales, Cardiff.
authors.forename: S
authors.initials: S
authors.lastname: Jolles
authors.affiliation: Immunology, Salford Royal Foundation Trust, Manchester.
authors.forename: H
authors.initials: H
authors.lastname: Alachkar
authors.affiliation: Immunology, Addenbrookes Hospital, Cambridge.
authors.forename: D
authors.initials: D
authors.lastname: Kumaratne
authors.affiliation: Immunology, Papworth Hospital, Cambridge.
authors.forename: H
authors.initials: H
authors.lastname: Baxendale
authors.affiliation: Regional Immunology Service, the Royal Hospitals, Belfast.
authors.forename: J D
authors.initials: JD
authors.lastname: Edgar
authors.affiliation: Department of Immunology, Manchester Royal Infirmary, Manchester.
authors.forename: M
authors.initials: M
authors.lastname: Helbert
authors.affiliation: Primary Immunodeficiency Group, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: S
authors.initials: S
authors.lastname: Hambleton
authors.affiliation: Paediatric Allergy and Immunology, University of Manchester, Manchester.
authors.forename: P D
authors.initials: PD
authors.lastname: Arkwright
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D001987:Bronchiectasis / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D017074:Common Variable Immunodeficiency / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012042:Registries; D012141:Respiratory Tract Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D006113:United Kingdom
chemical_list: D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous
keywords: bronchiectasis; cancer; common variable immunodeficiency; idiopathic hypogammagloblinaemia