Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.

Peter Olofsson; Jens Holmberg; Jesper Tordsson; Shemin Lu; Bo Åkerström; Rikard Holmdahl

doi:10.1038/ng1058

Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.

Peter Olofsson, Jens Holmberg, Jesper Tordsson, Shemin Lu, Bo Åkerström, Rikard Holmdahl

Infection Medicine (BMC)

Research output: Contribution to journal › Article › peer-review

Abstract

The identification of genes underlying quantitative-trait loci (QTL) for complex diseases, such as rheumatoid arthritis, is a challenging and difficult task for the human genome project. Through positional cloning of the Pia4 QTL in rats, we found that a naturally occurring polymorphism of Ncf1 (encoding neutrophil cytosolic factor 1, a component of the NADPH oxidase complex) regulates arthritis severity. The disease-related allele of Ncf1 has reduced oxidative burst response and promotes activation of arthritogenic T cells. Pharmacological treatment with substances that activate the NADPH oxidase complex is shown to ameliorate arthritis. Hence, Ncf1 is associated with a new autoimmune mechanism leading to severe destructive arthritis, notably similar to rheumatoid arthritis in humans.

Original language	English
Pages (from-to)	25-32
Journal	Nature Genetics
Volume	33
Issue number	1
DOIs	https://doi.org/10.1038/ng1058
Publication status	Published - 2003

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Division of Infection Medicine (BMC) (013024020), Medical Inflammation Research (013212019)

Subject classification (UKÄ)

Immunology in the Medical Area (including Cell and Immunotherapy)
Infectious Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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abstract = "The identification of genes underlying quantitative-trait loci (QTL) for complex diseases, such as rheumatoid arthritis, is a challenging and difficult task for the human genome project. Through positional cloning of the Pia4 QTL in rats, we found that a naturally occurring polymorphism of Ncf1 (encoding neutrophil cytosolic factor 1, a component of the NADPH oxidase complex) regulates arthritis severity. The disease-related allele of Ncf1 has reduced oxidative burst response and promotes activation of arthritogenic T cells. Pharmacological treatment with substances that activate the NADPH oxidase complex is shown to ameliorate arthritis. Hence, Ncf1 is associated with a new autoimmune mechanism leading to severe destructive arthritis, notably similar to rheumatoid arthritis in humans.",

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AU - Lu, Shemin

AU - Åkerström, Bo

AU - Holmdahl, Rikard

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Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.

Abstract

Bibliographical note

Subject classification (UKÄ)

UN SDGs

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