Antibody repertoire analysis in polygenic autoimmune diseases

18 May 2018

High-throughput sequencing of the DNA/RNA encoding antibody heavy and light chains is rapidly transforming the field of adaptive immunity. It can address key questions including (i) how the B-cell repertoire differs in health and disease and (ii) if it does differ, the point(s) in B-cell development at which this occurs. The advent of technologies, such as whole genome sequencing, offers the chance to link abnormalities in the B-cell antibody repertoire to specific genomic variants and polymorphisms. Here, we discuss the current research using B-cell antibody repertoire sequencing in three polygenic autoimmune diseases where there is good evidence for a pathological role for B-cells, namely systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. These autoimmune diseases exhibit significantly skewed B-cell receptor repertoires compared to healthy controls. Interestingly, some common repertoire defects are shared between diseases, such as elevated IGHV4-34 gene usage. B-cell clones have effectively been characterised and tracked between different tissues and blood in autoimmune disease. It has been hypothesised that these differences may signify differences in B-cell tolerance, however, the mechanisms and implications of these defects are not clear.