B‐cell receptor repertoire sequencing in patients with primary immunodeficiency: a review. Issue 2 (18th December 2017)

• Record Type: Journal Article
• Authors: Ghraichy, Marie; Galson, Jacob D.; Kelly, Dominic F.; Trück, Johannes
• Is Part Of: Immunology. Volume 153:Issue 2(2018)
• Page Start: 145
• Page End: 160
• Publication Date: 2017-12-18
• Subjects: antibody disorder -- B‐cell receptor -- combined immunodeficiency -- next generation sequencing -- primary immunodeficiency -- repertoire; Immunology -- Periodicals
• DOI: 10.1111/imm.12865
• Languages: English
• ISSNs: 0019-2805

Abstract

Summary: The advent of next‐generation sequencing (NGS) now allows a detailed assessment of the adaptive immune system in health and disease. In particular, high‐throughput B‐cell receptor (BCR) repertoire sequencing provides detailed information about the functionality and abnormalities of the B‐cell system. However, it is mostly unknown how the BCR repertoire is altered in the context of primary immunodeficiencies (PID) and whether findings are consistent throughout phenotypes and genotypes. We have performed an extensive literature search of the published work on BCR repertoire sequencing in PID patients, including several forms of predominantly antibody disorders and combined immunodeficiencies. It is somewhat surprising that BCR repertoires, even from severe clinical phenotypes, often show only mild abnormalities and that diversity or immunoglobulin gene segment usage is generally preserved to some extent. Despite the great variety of wet laboratory and analytical methods that were used in the different studies, several findings are common to most investigated PIDs, such as the increased usage of gene segments that are associated with self‐reactivity. These findings suggest that BCR repertoire characteristics may be used to assess the functionality of the B‐cell compartment irrespective of the underlying defect. With the use of NGS approaches, there is now the opportunity to apply BCR repertoire sequencing to multiple patients and explore the PID BCR repertoire in more detail. Ultimately, using BCR repertoire sequencing in translational research could aid the management of PID patients by improving diagnosis, estimating functionality of the immune system and improving assessment of prognosis. Abstract : With the advent of next‐generation sequencing, large‐scale analysis of B‐cell receptor (BCR) repertoire sequencing becomes feasible and affordable, making it an optimal tool for translational research. Here, we summarize findings from previously conducted studies that have used BCR repertoire sequencing in patients with primary immunodeficiency (PID). Ultimately, this technique opens the opportunity to add to current management of PID patients by estimating the functionality of the B‐cell system and thereby improving diagnosis and management.