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Antibody repertoire analysis in polygenic autoimmune diseases

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Title: Antibody repertoire analysis in polygenic autoimmune diseases
Authors: Bashford-Rogers, RJM
Smith, KGC
Thomas, DC
Item 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.
Issue Date: 1-Sep-2018
Date of Acceptance: 6-Mar-2018
URI: http://hdl.handle.net/10044/1/78624
DOI: 10.1111/imm.12927
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.
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: RDA28
Keywords: 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
B-cell
B-cell receptors
antibodies
autoantibodies
autoimmunity
Antibodies
Autoimmune Diseases
High-Throughput Nucleotide Sequencing
Humans
Multifactorial Inheritance
Humans
Autoimmune Diseases
Antibodies
Multifactorial Inheritance
High-Throughput Nucleotide Sequencing
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
Immunology
1107 Immunology
1114 Paediatrics and Reproductive Medicine
Publication Status: Published
Online Publication Date: 2018-03-25
Appears in Collections:Department of Immunology and Inflammation