CXCL13 and CVID
Research type
Research Study
Full title
The Role of Chemokine (C-X-C motif) ligand 13 in the Pathogenesis of Common Variable Immunodeficiency
IRAS ID
232824
Contact name
Mohammad A A Ibrahim
Contact email
Sponsor organisation
King's College Hospital NHS Foundation Trust
Duration of Study in the UK
6 years, 0 months, 0 days
Research summary
The main role of CXCL13 is to attract B cells towards the sites of inflammation. It is mainly produced by the Tfh cells, but also by other cells of the immune system, e.g. myeloid cells. The Tfh cells provide help to B cells for antibody production against infections. Interestingly, in Common Variable Immunodeficiency (CVID) - a group of primary immunodeficiency disorders with defective antibody production – circulatory Tfh cells levels are raised. Moreover, CXCL13 is raised in various autoimmune disorders and a subset of CVID patients do present with autoimmune manifestations. \nThe NF-κB is a family of transcription factors, which mediate transcription of various genes, thus influencing multiple biologic processes, such as immune response. These factors can be activated via the canonical or the non-canonical pathway. Defects in components across the latter have been identified in several CVID patients. One of them was identified by our clinical research team. Mutations in this pathway may affect the dendritic cells (DCs) - another source of CXCL13 – which belong to the myeloid cells. Additionally, our research group has identified a skewing in the peripheral Tfh subsets of CVID patients, compared with healthy controls (HC). \nBecause of the above, we seek to explore the relationship of CXCL13 with CVID. I shall investigate, whether in CVID: a) CXCL13 is defective and this may contribute to antibody production failure, b) the myeloid cells have altered production and c) the above alterations are due to dysregulation of the non-canonical NF-kB pathway in those cells. \nHence, I shall initially compare the serum CXCL13 levels in CVID patients to HC, then the efficiency of CXCL13 secretion by myeloid cells between CVID and HC, and should these become established, I shall try correlating the efficiency of the non-canonical pathway in myeloid cells with CXCL13 secretion in CVID and HC.\n
REC name
Yorkshire & The Humber - Bradford Leeds Research Ethics Committee
REC reference
20/YH/0015
Date of REC Opinion
28 Jan 2020
REC opinion
Favourable Opinion