Lymphocyte Immunophenotyping in Common Variable Immunodeficiency

Investigation of the Lymphocyte Surface Expression of Patients With Primary Immunodeficiency (Common Variable Immunodeficiency (CVID)), Compared to Controls

The purpose of this study is to discover if differences in the surface markers of B-cells (antibody producing cells of the immune system) in Common Variable Immune Deficiency (CVID) are related to CVID or its complications/treatment (e.g. bronchiectasis, granulomatous disease, immunoglobulin treatment).

The study hypothesis is that the altered B-cell surface markers are related to CVID, and not to the complications or treatment of CVID.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis; Common Variable Immunodeficiency; Granulomatous Disease; Immunoglobulin Treatment

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 210

Contacts and Locations

• Study Contact: Name: Philip Bright, MBBS; Phone Number: 02032460282; Email: philip.bright@bartsandthelondon.nhs.uk
• Study Contact Backup: Name: Matthew S Buckland, MBBS; Phone Number: 02032460282/5; Email: mbuckland@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom, E1 1BB
    • Barts and the London NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients selected from medical clinics in the order of attendance with common variable immunodeficiency, bronchiectasis, on long-term immunoglobulin treament and granulomatous disease. Must be able to give consent for testing of B-cell immunophenotype. Healthy control samples taken from colleagues.

Description

Inclusion Criteria:

• 18 or over
• Competent to consent
• Have diagnosis of Common Variable Immunodeficiency, granulomatous disease, on long term immunoglobulin or bronchiectasis.

Exclusion Criteria:

• Under 18
• Unable to consent.
• Medical problem that could alter B-cell immunophenotype (except for the diagnoses in the inclusion criteria)/

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort
Healthy Controls
CVID; Patients with common variable immunodeficiency
CVID and granulomatous disease; Patients with CVID complicated with granulomatous inflammation
CVID and bronchiectasis; Patients with CVID complicated by bronchiectasis
Control on Immunoglobulin; Patients on immunoglobulin long-term who do not have an immunodeficiency
Control bronchiectasis; Controls with bronchiectasis not caused by a known immunodeficiency
Control with granulomatous disease; Control patients with Crohn's Disease as this is a disease that causes granulomatous inflammation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of B-cells of all lymphocytes	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.	5 months
Percentage of class switched memory B-cells as a percentage of B-cells	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.	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage expression of CD21 and CD38	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.	5 months

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust

Publications and helpful links

General Publications

• Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, Vlkova M, Hernandez M, Detkova D, Bos PR, Poerksen G, von Bernuth H, Baumann U, Goldacker S, Gutenberger S, Schlesier M, Bergeron-van der Cruyssen F, Le Garff M, Debre P, Jacobs R, Jones J, Bateman E, Litzman J, van Hagen PM, Plebani A, Schmidt RE, Thon V, Quinti I, Espanol T, Webster AD, Chapel H, Vihinen M, Oksenhendler E, Peter HH, Warnatz K. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008 Jan 1;111(1):77-85. doi: 10.1182/blood-2007-06-091744. Epub 2007 Sep 26.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): December 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: September 6, 2010
• First Submitted That Met QC Criteria: September 7, 2010
• First Posted (Estimated): September 8, 2010

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: bronchiectasis; common variable immunodeficiency; granulomatous disease; crohns disease; immunoglobulin replacement or treatment; B-cell immunophenotyping
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Bronchial Diseases; Bronchiectasis; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency
• Other Study ID Numbers: 006749