# Neutrophils of lupus patients carry aberrant RNA splicing that yields neoantigens for T cells

- Published: 2026-11-05 03:55 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: systemic lupus erythematosus, aberrant RNA splicing, neutrophils, neoantigens, cryptic splicing events, RiboSplitter, interferon-γ, IgG autoantibodies, MHC class I peptides, autoimmunity
- URL: https://realtech.media/news/rt-8ecb4ae73f4fa34da41f4854_neutrophils_of_lupus/

**In blood samples from 34 patients with systemic lupus erythematosus, Nature authors found 271 splicing events absent in controls; peptides from them activated T cells in vitro.**

![Neutrophils of lupus patients carry aberrant RNA splicing that yields neoantigens for T cells](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/db039d37043f5810.png)
*nature.com*

A team from the La Jolla Institute for Immunology and the University of Washington reported that neutrophils from patients with systemic lupus erythematosus (SLE) contain aberrantly spliced transcripts that are translated into novel amino acid sequences. The work was published in Nature (nature.com) and used blood samples from 34 patients with SLE, 20 healthy donors and 15 patients with rheumatoid arthritis [1]. According to the SciTechDaily summary, 33 of the 34 patients had such abnormalities.

The authors sequenced neutrophil RNA to a depth of about 50 million reads with a read length of 101 bp. Using their RiboSplitter pipeline, they characterized 65,730 high-confidence alternative splicing events in 5,697 protein-coding genes; 521 events in 356 genes differed significantly from healthy donors [1].

## Cryptic splicing in SLE neutrophils

With a threshold of at least five reads, the team detected 271 cryptic splicing events in 130 genes in SLE neutrophils. None of them was found in healthy donors or patients with rheumatoid arthritis [1]. The most common events were abnormal exon skips, followed by multi-exon skips, atypical 5′ or 3′ splice sites and intron retention.

The affected genes were biased toward type I interferon-inducible ones. The most frequently mis-spliced were IFI44L, MX1, OAS1, RSAD2, XAF1, IFI27 and IFIT1. Cryptic events also occurred in genes not considered interferon-inducible, such as ABCG1, PSMF1 and OGG1. Read support for events that generated novel peptide sequences ranged from 283 reads to the cut-off of 5, with a median of 10 [1].

## Immune response to the new peptides

Mass spectrometry detected 21 peptides derived from the novel sequences on class I major histocompatibility complex molecules in patient samples. When T cells from patients were co-cultured with overlapping 15-mer peptides from these sequences, CD4+ and CD8+ T cells expanded and rapidly secreted interferon-γ on reactivation [1].

T cell receptor sequencing and re-expression transferred neoantigen reactivity to a reporter T cell. Serum from patients with SLE also contained IgG autoantibodies that recognized epitopes within the novel sequences [1].

The authors conclude that dysregulated mRNA splicing in SLE neutrophils generates neoantigens associated with T and B cell activation, clonal expansion, IgG class switching and autoimmunity [1]. The experiments were performed on patient-derived samples and cells in vitro.

## Sources

1. [nature.com](https://www.nature.com/articles/s41586-026-11219-7)
2. [SciTechDaily](https://scitechdaily.com/33-out-of-34-lupus-patients-shared-an-immune-cell-abnormality)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-8ecb4ae73f4fa34da41f4854_neutrophils_of_lupus/