Immunoglobulin UMI sequencing from human gut

Dataset overview

Participants 4

Samples 42

Reuse readiness 6.3/10 evidence-backed score

Immunomolecular and reactivity landscapes of gut IgA subclasses in homeostasis and inflammatory bowel disease.

Tejedor Vaquero S, Neuman H, Comerma L, Marcos-Fa X, Corral-Vazquez C, Uzzan M, Pybus M, Segura-Garzón D, et al. · The Journal of experimental medicine · 2024

Abstract

The human gut includes plasma cells (PCs) expressing immunoglobulin A1 (IgA1) or IgA2, two structurally distinct IgA subclasses with elusive regulation, function, and reactivity. We show here that intestinal IgA1+ and IgA2+ PCs co-emerged early in life, comparably accumulated somatic mutations, and were enriched within short-lived CD19+ and long-lived CD19- PC subsets, respectively. IgA2+ PCs were extensively clonally related to IgA1+ PCs and a subset of them presumably emerged from IgA1+ precursors. Of note, secretory IgA1 (SIgA1) and SIgA2 dually coated a large fraction of mucus-embedded bacteria, including Akkermansia muciniphila. Disruption of homeostasis by inflammatory bowel disease (IBD) was associated with an increase in actively proliferating IgA1+ plasmablasts, a depletion in long-lived IgA2+ PCs, and increased SIgA1+SIgA2+ gut microbiota. Such increase featured enhanced IgA1 reactivity to pathobionts, including Escherichia coli, combined with depletion of beneficial A. muciniphila. Thus, gut IgA1 and IgA2 emerge from clonally related PCs and show unique changes in both frequency and reactivity in IBD.

doi:10.1084/jem.20230079 ↗ PMID 39560666 ↗ PMC11577441 ↗

Study facts

Organism: —
Platform: Illumina MiSeq
Age group: adult
Disease groups: —
Anatomical sites: —

Data availability

Analysis code

Strengths & limitations for reuse

Strengths

Raw reads are advertised
Analysis code is available
Participant counts are documented
Sample counts are documented

Limitations

Not documented: feature/otu tables are advertised
Not documented: taxonomic tables are advertised

Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

Field	Value	Evidence
`assay.paired_end`	True	Single-strand products were paired-end sequenced on a MiSeq instrument (Illumina) with the 600 Cycle v2 Kit (2 × 300 bp). Section `Sequencing of Ig gene repertoires`, offset 109677
`assay.platform`	Illumina MiSeq from source	ENA instrument_model=Illumina MiSeq Section `ENA study report`, offset —
`assay.primers_reported`	True	specific for the framework region 1 of VH1, VH2, VH3, VH4, VH5, or VH6... specific for Cα, Cμ, or Cγ Section `Sequencing of Ig gene repertoires`, offset 109113
`assay.read_length`	300	Single-strand products were paired-end sequenced on a MiSeq instrument (Illumina) with the 600 Cycle v2 Kit (2 × 300 bp). Section `Sequencing of Ig gene repertoires`, offset 109677

Cohort

Field Value Evidence

Field	Value	Evidence
`cohort.age_group`	adult	sorted from the terminal ileum and ascending colon of four adults. Section `dataset-authority study description`, offset 1727
`cohort.study_design`	cross_sectional inferred	Histologically normal tissue samples from the terminal ileum and ascending colon were obtained from 40 patients... Section `Human tissue and blood specimens`, offset 84244
`cohort.total_participants`	4	In total, 10,182,511 Ig heavy chain variable (IGHV) gene sequences from 4 donors were obtained through next generation sequencing (NGS). Section `dataset-authority study description`, offset 1906

cohort.age_group

adult

sorted from the terminal ileum and ascending colon of four adults.

Section dataset-authority study description, offset 1727

cohort.study_design

cross_sectional inferred

Histologically normal tissue samples from the terminal ileum and ascending colon were obtained from 40 patients...

Section Human tissue and blood specimens, offset 84244

cohort.total_participants

4

In total, 10,182,511 Ig heavy chain variable (IGHV) gene sequences from 4 donors were obtained through next generation sequencing (NGS).

Section dataset-authority study description, offset 1906

Data_Assets

Field	Value	Evidence
`data_assets.analysis_code`	True	Mehr lab scripts mentioned in the section on lineage tree-based analysis are available ... upon request. Section `Data availability`, offset 127025
`data_assets.open_access`	True	Ig gene and 16s RNA sequencing data are publicly available at NCBI’s Sequence Read Archive, accession codes PRJNA596067 and PRJNA902959, respectively. Section `Data availability`, offset 126746
`data_assets.pipeline_or_tool_versions`	True	processed using pRESTO ... version 0.5.8 Section `Data preprocessing`, offset 112500
`data_assets.qc_or_negative_controls_reported`	True	removing reads with average Phred scores <20 Section `Data preprocessing`, offset 112636
`data_assets.raw_reads`	True	Ig gene and 16s RNA sequencing data are publicly available at NCBI’s Sequence Read Archive, accession codes PRJNA596067 and PRJNA902959, respectively. Section `Data availability`, offset 126746

Specimens

Field Value Evidence

Field	Value	Evidence
`specimens.body_site`	terminal ileum and ascending colon	B cells and PCs sorted from the terminal ileum and ascending colon of four adults. Section `dataset-authority study description`, offset 1680
`specimens.number_of_samples`	42 from source	ENA sample_count=42 Section `ENA study report`, offset —
`specimens.sample_type`	mucosal_biopsy inferred	Histologically normal tissue samples from the terminal ileum and ascending colon were obtained from 40 patients. Section `Human tissue and blood specimens`, offset 84244

specimens.body_site

terminal ileum and ascending colon

B cells and PCs sorted from the terminal ileum and ascending colon of four adults.

Section dataset-authority study description, offset 1680

specimens.number_of_samples

42 from source

ENA sample_count=42

Section ENA study report, offset —

specimens.sample_type

mucosal_biopsy inferred

Histologically normal tissue samples from the terminal ileum and ascending colon were obtained from 40 patients.

Section Human tissue and blood specimens, offset 84244