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Inflammatory arthritis immune related adverse events represent a unique autoimmune disease entity primarily driven by T cells, but likely not autoantibodies

GSE322576 Homo sapiens (human) RNA-seq (gene expression) 38 samples Submitted 2026/03/07 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 38 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
38 samples: 8 conditions, mostly in duplicateGroups 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
Inflammatory arthritis irAE may represent a unique autoimmune disease primarily driven by T cells but likely not autoantibodiesScience advances · 2026
Summary (written by the submitters)
Immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA) is an increasingly recognized immune-related adverse event (irAE), yet its underlying immunopathogenesis remains poorly understood. Unlike rheumatoid arthritis (RA), where autoantibodies and B cell dysfunction are central features, the contribution of humoral immunity to IA irAE is unclear.
Read the full summary ↓
Here, we performed in-depth immunophenotyping of peripheral blood from patients with IA irAE, and compared them with seronegative RA patients, ICI-treated patients without irAE, and healthy controls. IA irAE was marked by a distinct T cell-dominated profile, with CD4+ T cells exhibiting reduced CXCR3 and CCR6 expression, and both CD4+ and CD8+ T cells showing increased cytotoxic molecule expression and metabolic activation. In contrast to seronegative RA, IA irAE patients displayed no significant elevation in autoantibody levels or atypical CD11c+CD21- B cells. IA irAE was further characterized by a proinflammatory cytokine milieu, with elevated levels of IL-6, IL-12, and type I IFN, which correlated with the observed T cell activation phenotypes. Altogether, our findings define IA irAE as an immunologically distinct entity from RA, representing a naturally occurring model of antibody-independent systemic autoimmunity in humans. These results suggest that pathogenic T cell responses, potentiated by specific inflammatory cytokines, may be sufficient to drive arthritis in the absence of humoral autoimmunity, offering new insights into immune tolerance breakdown and therapeutic targeting in irAEs.
Published in
Inflammatory arthritis irAE may represent a unique autoimmune disease primarily driven by T cells but likely not autoantibodies
Zhu X, Yu Y, Chen S et al. · Science advances 2026 · PMID 41920990 · doi:10.1126/sciadv.aea4262
This dataset
Open GSE322576 in finder → Find more human RNA-seq datasets →
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.

Series matrix ↓
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 GSE322576_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
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.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1353895 and SRA study SRP639892. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41920990) ↗
Study design
8 conditions, mostly in duplicate
GEX_ANRF ×8 TCR_ANRF ×8 GEX_H ×3 TCR_H ×3 GEX_ICI ×2 GEX_irAE ×2 TCR_ICI ×2 TCR_irAE ×2 +8 more

Supports a between-group comparison across 30 samples.

How we read this: 8 replicated groups read from 38 sample titles; they account for 30 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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