Evidence map›Paper›PMID 24517398›Full record

Trial reportArthritis research & therapy2014

Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren's syndrome.

Uri Hershberg, Wenzhao Meng, Bochao Zhang, Nancy Haff, E William St Clair, Philip L Cohen, Patrice D McNair, Ling Li, Marc C Levesque, Eline T Luning Prak

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. CD27 on human memory B cells-more than just a surface marker.Clinical and experimental immunology · 2023
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. The analysis of clonal expansions in normal and autoimmune B cell repertoires.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 1 country.

Uri Hershberg
Wenzhao Meng
Bochao Zhang
Nancy Haff
E William St Clair
Philip L Cohen
Patrice D McNair
Ling Li
Marc C Levesque
Eline T Luning Prak
University of Pennsylvania · USDrexel University · USUniversity of Pittsburgh · USDuke Medical Center · USDuke University Hospital · USTemple University · US

Funding

Supplement - Inflammatory Triggers in B Cell AutoimmunityU19AI056363 · NIAID · DUKE UNIVERSITY · PI ST. CLAIR, EUGENE WILLIAM · 2003 to 2017
$35.3M
NIAID NIH HHS U19 AI-056363
6 · The paper itself

Abstract

introductionSubjects with primary Sjögren's syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab.

methodsTo determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period.

resultsExpanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection.

conclusionsFor some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an expanded clone may provide a novel means of measuring the chronicity and selection of expanded B-cell populations in humans.

Indexed as

Antibodies, Monoclonal, Murine-DerivedAntirheumatic AgentsB-LymphocytesClone CellsFlow CytometryGenes, Immunoglobulin Heavy ChainHumansRituximabSjogren's SyndromeAntibodies, Monoclonal, Murine-DerivedAntirheumatic AgentsRituximab

Identifiers

PMID24517398
PMCPMC3978607
OpenAlexW2157080844

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.