A unique antibody gene signature is prevalent in the central nervous system of patients with multiple sclerosis

Abstract

B cells isolated from the CSF of patients with multiple sclerosis (MS) have a unique accumulation of somatic hypermutation, within the B cell receptor, termed the antibody gene signature (AGS). The focus of this study was to investigate whether the AGS could also be detected in MS brain tissue. Genetic analysis of B cells isolated from post-mortem CNS tissue samples from four MS brains demonstrated that signature enriched B cells are present at the site of tissue injury as well as in the circulating CSF.

Intrathecal BCR transcriptome in multiple sclerosis versus other neuroinflammation: Equally diverse and compartmentalized, but more mutated, biased and overlapping with the proteome

“…The IGHV transcriptome in CSF of MS patients did, however, to a larger extent reflect intrathecal synthesis of IgG, and was characterized by more pronounced affinity maturation and selective use of IGHV4 genes. It has previously been reported that IGHV transcripts recovered from CSF and CNS B cells of MS patients have undergone somatic hypermutation [16,22,23,[33][34][35], have biased IGHV gene usage [15,20], match CSF IgG [19,21], and communicate across the blood-brain barrier [20,21,23,35]. The sequencing depth achieved using Illumina technology, combined with mass-spectrometric verification, allowed us to extend these findings by showing that all examined MS patients, regardless of disease duration and therapy, had closely related IGH-VDJ transcripts on both sides of the blood-CSF barrier.…”

Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation

“…77 Sequences were analyzed and compiled into databases containing VH gene, JH gene, CDR3 amino-acid sequence and mutation information using a Perl program developed at UTSWMC 78 that utilizes the IMGT/V-QUEST tool as a basis for extracting the sequence information. Sequences with o85% homology to their VH germline gene segment were dismissed to avoid introducing potential VH gene miscalls into the databases.…”

Intrathecal IgG Synthesis: A Resistant and Valuable Target for Future Multiple Sclerosis Treatments

“…As a consequence, each patient has a unique pattern “OCB fingerprint” of CSF immunoglobulins [ 20 , 21 ]. This biological signature may be scored according to the typical positions of mutational replacements (hotspots) on IgG and can be used as a composite signature Z -score, which is highly predictive of the conversion of clinically isolated syndromes (CIS) to clinically defined MS [ 22 , 23 ]. These hotspot codons reside in the complementary determining region (CDR) where they are predicted to have contact with the (unknown) antigen(s).…”