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The Investigation of Autoimmunity and B Cell Characteristics in Common Variable Immunodeficiency Patients

Wanders, J; (2013) The Investigation of Autoimmunity and B Cell Characteristics in Common Variable Immunodeficiency Patients. Masters thesis (M.Phil), UCL (University College London). Green open access

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Abstract

Common Variable Immune Deficiency (CVID) is characterized by hypogammaglobulinemia and impaired antibody responses to vaccination. Ten percent of CVID patients have low B cell counts and 20-30 % develop autoimmune conditions, mainly idiopathic thrombocytopenic purpura (ITP), autoimmune haemolytic anaemia (AIHA) and thyroiditis. Eight to ten percent of CVID patients carry mutations in TACI while the majority of these patients have autoimmune manifestations. The aim of this study was to investigate why some CVID patients have low B cell numbers. One hypothesis is that they have auto-antibodies against B cells, which would make CVID a primary autoimmune condition that could explain the hypogammaglobulinaemia through autoimmunity. Alternatively, they might have reduced levels of B cell survival factors. To detect auto-antibodies in the serum of patients, a FACS-based assay was developed. B cells from healthy donors were incubated with patients’ sera and stained with anti- human CD19, - IgM and –IgG antibodies. Thirty-six CVID patients with low B cell numbers, autoimmune manifestation or both were screened. None were found to have IgM or IgG anti-B cell auto-antibodies. To explore the second hypothesis, serum levels of the B cell activating factor BAFF were analyzed. One group of patients with extremely low BAFF levels and a second group with highly elevated BAFF levels were found. B cell phenotypes and BAFF serum levels were used to select patients for sequencing BAFF, or BAFF receptor (BAFF-R) for possible mutations. The coding regions of BAFF were sequenced in 19 patients with low BAFF levels and all showed wild type sequences. In 17 patients with high BAFF levels, coding regions of BAFF-R were sequenced. Five patients showed previously described rare polymorphisms; four had a heterozygous P21R and one had a heterozygous G64V polymorphism. The novel heterozygous R106Q polymorphism was detected in one patient. The surface expression of BAFF-R on B cells from patients with rare polymorphisms showed no major impairment compared to healthy individuals.

Type: Thesis (Masters)
Qualification: M.Phil
Title: The Investigation of Autoimmunity and B Cell Characteristics in Common Variable Immunodeficiency Patients
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: CVID, BAFF, Autoimmunity, BAFF-R
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/1384661
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