title: Common variable immunodeficiency disorders: division into distinct clinical phenotypes.
abstract: The European Common Variable Immunodeficiency Disorders registry was started in 1996 to define distinct clinical phenotypes and determine overlap within individual patients. A total of 7 centers contributed patient data, resulting in the largest cohort yet reported. Patients (334), validated for the diagnosis, were followed for an average of 25.6 years (9461 patient-years). Data were used to define 5 distinct clinical phenotypes: no complications, autoimmunity, polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. A total of 83% of patients had only one of these phenotypes. Analysis of mortality showed a considerable reduction in the last 15 years and that different phenotypes were associated with different survival times. Types of complications and clinical phenotypes varied significantly between countries, indicating the need for large, international registries. Ages at onset of symptoms and diagnosis were shown to have a Gaussian distribution, but were not useful predictors of phenotype. The only clinical predictor was polyclonal lymphocytic infiltration, which was associated with a 5-fold increased risk of lymphoid malignancy. There was widespread variation in the levels of serum immunoglobulin isotypes as well as in the percentages and absolute numbers of B cells, confirming the heterogeneity of these conditions. Higher serum IgM and lower circulating CD8 proportions were found to be predictive markers for polyclonal lymphocytic infiltration and autoimmunity, respectively.
authors.affiliation: Department of Clinical Immunology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. helen.chapel@ndm.ox.ac.uk
authors.forename: Helen
authors.initials: H
authors.lastname: Chapel
authors.forename: Mary
authors.initials: M
authors.lastname: Lucas
authors.forename: Martin
authors.initials: M
authors.lastname: Lee
authors.forename: Janne
authors.initials: J
authors.lastname: Bjorkander
authors.forename: David
authors.initials: D
authors.lastname: Webster
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Vojtech
authors.initials: V
authors.lastname: Thon
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Abedi
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarstrom
mesh_terms: D017668:Age of Onset; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D017074:Common Variable Immunodeficiency / Q000145:classification* / Q000150:complications / Q000401:mortality / Q000473:pathology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D017254:Leukemic Infiltration; D010641:Phenotype; D011379:Prognosis; D012042:Registries
chemical_list: D007132:Immunoglobulin Isotypes