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IgA autoantibodies trigger pro-inflammatory, pro-fibrotic and type I interferon responses in Hidradenitis suppurativa skin lesion

GSE298444 Homo sapiens (human) Single-cell RNA-seq 24 samples Submitted 2026/03/04 Platform GPL34284
At a glance

Single-cell RNA-seq · human · 24 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
24 samples: 6 conditions, mostly with about 4 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
IgA autoantibodies promote inflammation, Th17 polarization and fibrotic responses in hidradenitis suppurativaNature communications · 2026
Summary (written by the submitters)
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with complex immune dysregulation. While previous studies have reported tertiary lymphoid structures (TLS) and IgA-producing B cells in HS lesions, the pathogenic role of IgA autoantibodies remains poorly understood. Here, we demonstrate that lesional HS skin exhibits elevated expression of IGHA1, IGHA2, and J chain, as confirmed by qPCR, immunofluorescence, and western blot analyses.
Read the full summary ↓
Single-cell RNA sequencing identified local plasma and B cells as the primary source of IgA. Autoantigen profiling revealed a diverse repertoire of IgA autoantibodies targeting nuclear, cytoplasmic, and membrane antigens, including MDA5, complement C3/C4, NLRP1, and ACE, with levels correlating with disease severity. We identified IgA autoantibodies targeting CD68⁺ macrophages, which induced secretion of TNF, IL-6, and IL-1β, and upregulated inflammasome and fibrotic pathways. Anti-NET IgA was elevated in HS and promoted NET formation, establishing a pathogenic feedback loop. NET–IgA immune complexes activated M2 macrophages to secrete CCL18, driving collagen production by fibroblasts and promoting a type I IFN signature. IgA immune complexes presented by myeloid dendritic cells activated CD4⁺ T cells, triggering IFN-γ production, further amplifying local inflammation. Direct exposure of fibroblasts to NET–IgA complexes triggered expression of adhesion molecules, chemokines, and regulators of adaptive immunity. Together, these findings uncover a novel role for IgA autoantibodies in HS, implicating them as central drivers of chronic inflammation, fibrosis, and immune crosstalk across neutrophils, macrophages, fibroblasts, and T cells.
Published in
IgA autoantibodies promote inflammation, Th17 polarization and fibrotic responses in hidradenitis suppurativa
Carmona-Rivera C, O'Neil LJ, Patino-Martinez E et al. · Nature communications 2026 · PMID 41876535 · doi:10.1038/s41467-026-70883-5
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE298444_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1269466 and SRA study SRP588516. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly with about 4 replicates each
M2 + ctrl IgA ×4 M2 + HS IgA ×4 ctrl Skin firboblasts + NETs ×4 ctrl Skin firboblasts + NETs + HS IgA ×4 ctrl Skin fibroblasts + supernatants of macro… ×4 ctrl Skin fibroblasts + supernatants of macro… ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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