Antibody repertoire analysis in polygenic autoimmune diseases
File(s)
Author(s)
Bashford-Rogers, Rachael JM
Smith, Kenneth GC
Thomas, David C
Type
Journal Article
Abstract
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 with healthy controls. Interestingly, some common repertoire defects are shared between diseases, such as elevated IGHV4‐34 gene usage. B‐cell clones have effectively been characterized and tracked between different tissues and blood in autoimmune disease. It has been hypothesized that these differences may signify differences in B‐cell tolerance; however, the mechanisms and implications of these defects are not clear.
Date Issued
2018-09-01
Date Acceptance
2018-03-06
Citation
Immunology, 2018, 155 (1), pp.3-17
ISSN
0019-2805
Publisher
Wiley
Start Page
3
End Page
17
Journal / Book Title
Immunology
Volume
155
Issue
1
Copyright Statement
© 2018 The Authors. Immunology Published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000442213700002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
RDA28
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
antibodies
autoantibodies
autoimmunity
B-cell
B-cell receptors
SYSTEMIC-LUPUS-ERYTHEMATOSUS
B-CELL REPERTOIRE
LYMPHOID TYROSINE PHOSPHATASE
IMMUNOGLOBULIN-KAPPA-CHAIN
MYELIN BASIC-PROTEIN
V-H REPLACEMENT
MULTIPLE-SCLEROSIS
RHEUMATOID-ARTHRITIS
GENE SEGMENT
CEREBROSPINAL-FLUID
Publication Status
Published
Date Publish Online
2018-03-25