Large overlap in neutrophil transcriptome between lupus and COVID-19 with limited lupus-specific gene expression
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ..
OBJECTIVES: To illuminate the poorly understood aetiology of SLE by comparing the gene expression profile of SLE neutrophils with that of neutrophils from patients infected by SARS-CoV-2, a disease (COVID-19) with well-defined antigens and a similar type I interferon response.
METHODS: RNA sequencing of neutrophils from patients with SLE (n=15) and healthy controls (n=12) was analysed for differential gene expression and modulated pathways. The same analyses were performed on a similar neutrophil dataset from patients with SARS-CoV-2 infection (n=30) and healthy controls (n=8). Next, we carried out comparative analyses to identify common and unique transcriptional changes between the two disease contexts, emphasising genes regulated in opposite directions.
RESULTS: We identified 372 differentially expressed genes in SLE neutrophils compared with healthy donor neutrophils (≥2 fold, p<0.05), 181 of which were concordant with transcriptional changes in SARS-CoV-2-infected individuals compared with their respective healthy controls. In contrast, 118 genes demonstrated statistically significant alterations exclusive to SLE, including 28 genes that were differentially expressed in opposite directions in the two diseases.
CONCLUSIONS: The substantial overlap between neutrophil responses in SLE and COVID-19 suggests that the unknown cause of SLE is functionally similar to a viral infection and drives a similar immune activation and type I interferon response. Conversely, the genes regulated in the opposite direction represent responses unique to SLE. These include tyrosylprotein sulfotransferase-1 and nucleic acid deaminases of the APOBEC family, which can catalyse cytosine-to-uridine editing of both RNA and DNA, and other RNA-modifying enzymes.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
Lupus science & medicine - 11(2024), 1 vom: 31. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Najjar, Rayan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
63231-63-0 |
|---|
| Anmerkungen: |
Date Completed 05.02.2024 Date Revised 10.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1136/lupus-2023-001059 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367914972 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367914972 | ||
| 003 | DE-627 | ||
| 005 | 20240210233214.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240202s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/lupus-2023-001059 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1287.xml |
| 035 | |a (DE-627)NLM367914972 | ||
| 035 | |a (NLM)38302132 | ||
| 035 | |a (PII)e001059 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Najjar, Rayan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Large overlap in neutrophil transcriptome between lupus and COVID-19 with limited lupus-specific gene expression |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 05.02.2024 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. | ||
| 520 | |a OBJECTIVES: To illuminate the poorly understood aetiology of SLE by comparing the gene expression profile of SLE neutrophils with that of neutrophils from patients infected by SARS-CoV-2, a disease (COVID-19) with well-defined antigens and a similar type I interferon response | ||
| 520 | |a METHODS: RNA sequencing of neutrophils from patients with SLE (n=15) and healthy controls (n=12) was analysed for differential gene expression and modulated pathways. The same analyses were performed on a similar neutrophil dataset from patients with SARS-CoV-2 infection (n=30) and healthy controls (n=8). Next, we carried out comparative analyses to identify common and unique transcriptional changes between the two disease contexts, emphasising genes regulated in opposite directions | ||
| 520 | |a RESULTS: We identified 372 differentially expressed genes in SLE neutrophils compared with healthy donor neutrophils (≥2 fold, p<0.05), 181 of which were concordant with transcriptional changes in SARS-CoV-2-infected individuals compared with their respective healthy controls. In contrast, 118 genes demonstrated statistically significant alterations exclusive to SLE, including 28 genes that were differentially expressed in opposite directions in the two diseases | ||
| 520 | |a CONCLUSIONS: The substantial overlap between neutrophil responses in SLE and COVID-19 suggests that the unknown cause of SLE is functionally similar to a viral infection and drives a similar immune activation and type I interferon response. Conversely, the genes regulated in the opposite direction represent responses unique to SLE. These include tyrosylprotein sulfotransferase-1 and nucleic acid deaminases of the APOBEC family, which can catalyse cytosine-to-uridine editing of both RNA and DNA, and other RNA-modifying enzymes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Autoimmune Diseases | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Systemic Lupus Erythematosus | |
| 650 | 7 | |a RNA |2 NLM | |
| 650 | 7 | |a 63231-63-0 |2 NLM | |
| 650 | 7 | |a Interferon Type I |2 NLM | |
| 700 | 1 | |a Rogel, Noga |e verfasserin |4 aut | |
| 700 | 1 | |a Pineda, Jose Mario Bello |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaoxing |e verfasserin |4 aut | |
| 700 | 1 | |a Tran, Megan |e verfasserin |4 aut | |
| 700 | 1 | |a Bays, Alison |e verfasserin |4 aut | |
| 700 | 1 | |a Mustelin, Tomas |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Lupus science & medicine |d 2014 |g 11(2024), 1 vom: 31. Jan. |w (DE-627)NLM243194145 |x 2053-8790 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2024 |g number:1 |g day:31 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1136/lupus-2023-001059 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2024 |e 1 |b 31 |c 01 | ||