Role of non-canonical NF kappa B in T cell independent IgA production
Research type
Research Study
Full title
Investigating the role of defects in non-canonical nuclear factor kappa B signalling in deregulated T cell independent IgA production in CVID, Selective IgA deficiency and IgA Nephropathy patients
IRAS ID
215621
Contact name
Terrence Hunter
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 non-canonical nuclear factor kappa B pathway is an important cell-signalling pathway, which has a major role in determining how the normal immune system develops and functions. Studies in mice, investigating the function of this pathway have shown that this pathway has a critical role in regulating how much of the antibody, immunoglobulin A gets produced by B cells without the help of T cells.
These mouse papers came to the attention of the Immunodeficiency research group at King's College Hospital, led by Dr. Ibrahim, when a Common Variable Immunodeficiency (CVID) family was investigated. The group described a new genetic mutation in a gene called "NFKB2" that affects one of the key proteins in this pathway. The affected family members with this mutation produced no immunoglobulin A and immunoglobulin G and little immunoglobulin M. Other centres have also described this same genetic mutation in total of 20 CVID patients around the world.
In the literature, there is further evidence of other genetic mutations that affect other proteins in the non-canonical NF kappa B pathway in CVID patients. What is common with all of the patients with genetic mutations that affect this pathway is that the patients have problems with producing mature B cells that can make antibodies. However, nobody has worked out how, if at all, these genetic mutations stop B cells in affected patients producing antibodies.
In this study, we specifically want to investigate how defects in this pathway interfere with the production of immunoglobulin A when B cells don’t get help form T cells, and whether there is a genetic basis for this. We want to investigate this in CVID and Selective IgA deficiency patients, who don’t produce immunoglobulin A, and IgA Nephropathy and Henoch-Schonlein purpura patients, who produce excessive immunoglobulin A.
REC name
London - Chelsea Research Ethics Committee
REC reference
16/LO/2130
Date of REC Opinion
8 Dec 2016
REC opinion
Further Information Favourable Opinion