Lymphocyte Immunophenotyping in Common Variable Immunodeficiency

• Percentage of B-cells of all lymphocytes [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  Look at percentage of cells within the lymphocyte gate that express the B-cell marker CD19, and compare to healthy controls and non-healthy controls.
  
  
• Percentage of class switched memory B-cells as a percentage of B-cells [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  Percentage of class-switched memory B-cells (expressing CD27 and CD19), that do not express IgM or IgD, as a percentage of B-cells. This is reduced in CVID and this will be compared between controls and the patients with CVID.
  
  

• Percentage expression of CD21 and CD38 [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  Look for abnormalities in the CVID group and compare to control groups in the numeber of B-cells expressing low levels of CD21 (CD21 lo), and high CD38.
  
  

Common Variable Immune Deficiency (CVID) is a syndrome containing a spectrum of disorders which results in weakened immunity and recurrent infections. The ESID (European Society for Immunodeficiencies) CVID definition includes patients with marked decrease of IgG (at least 2 standard deviations below the mean for age). Patients must also have disease onset at an age over 2 years, absent isohaemagglutinins and/or response to vaccines and other defined causes of hypogammaglobulinaemia must be excluded. The Euroclass system of classifying CVID is the result of a European multicentre trial attempting to develop a consensus of two existing classification schemes of B-cell immunophenotyping. In this paper it was shown that B-cell immunophenotype correlated with coincidence of clinical sequelae and it suggested implementing this to further classify CVID to give prognostic and therapeutic information. However, it has not yet been shown that these alterations in B-cell immunophenotype are the result of CVID itself and not caused by the treatment or complications of CVID (e.g. immunoglobulin replacement therapy, granulomatous disease, bronchiectasis). The aim of this study is to show that alterations in B-cell immunophenotype are caused by CVID itself and not by its complications or treatment. The study will therefore compare CVID patients to suitable control patients with granulomatous disease, bronchiectasis and on long-term immunoglobulin therapy. A control group of normal people will also be included to ensure the assay can detect normality and to show differences between normal people and patients with CVID.