Dataset Information

PRF1 mutation alters immune system activation, inflammation, and risk of autoimmunity.

ABSTRACT:

Background

Defective alleles within the PRF1 gene, encoding the pore-forming protein perforin, in combination with environmental factors, cause familial type 2 hemophagocytic lymphohistiocytosis (FHL2), a rare, severe autosomal recessive childhood disorder characterized by massive release of cytokines-cytokine storm.

Objective

The aim of this study was to determine the function of hypomorph PRF1:p.A91V g.72360387 G > A on multiple sclerosis (MS) and type 1 diabetes (T1D).

Methods

We cross-compare the association data for PRF1:p.A91V mutation derived from GWAS on adult MS and pediatric T1D in Sardinians. The novel association with T1D was replicated in metanalysis in 12,584 cases and 17,692 controls from Sardinia, the United Kingdom, and Scotland. To dissect this mutation function, we searched through the coincident association immunophenotypes in additional set of general population Sardinians.

Results

We report that PRF1:p.A91V, is associated with increase of lymphocyte levels, especially within the cytotoxic memory T-cells, at general population level with reduced interleukin 7 receptor expression on these cells. The minor allele increased risk of MS, in 2903 cases and 2880 controls from Sardinia p = 2.06 × 10^-4, odds ratio OR = 1.29, replicating a previous finding, whereas it protects from T1D p = 1.04 × 10^-5, OR = 0.82.

Conclusion

Our results indicate opposing contributions of the cytotoxic T-cell compartment to MS and T1D pathogenesis.

SUBMITTER: Sidore C

PROVIDER: S-EPMC8044257 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

<i>PRF1</i> mutation alters immune system activation, inflammation, and risk of autoimmunity.

Sidore Carlo C Orrù Valeria V Cocco Eleonora E Steri Maristella M Inshaw Jamie Rj JR Pitzalis Maristella M Mulas Antonella A McGurnaghan Stuart S Frau Jessica J Porcu Eleonora E Busonero Fabio F Dei Mariano M Lai Sandra S Sole Gabriella G Virdis Francesca F Serra Valentina V Poddie Fausto F Delitala Alessandro A Marongiu Michele M Deidda Francesca F Pala Mauro M Floris Matteo M Masala Marco M Onengut-Gumuscu Suna S Robertson Catherine C CC Leoni Lidia L Frongia Annapaola A Ricciardi Maria Rossella MR Chessa Margherita M Olla Nazario N Lovicu Mario M Loizedda Annalisa A Maschio Andrea A Mereu Luisa L Ferrigno Paola P Curreli Nicolo N Balaci Lenuta L Loi Francesco F Ferreli Liana Ap LA Pilia Maria Grazia MG Pani Antonello A Marrosu Maria Giovanna MG Abecasis Goncalo R GR Rich Stephen S SS Colhoun Helen H Todd John A JA Schlessinger David D Fiorillo Edoardo E Cucca Francesco F Zoledziewska Magdalena M

Multiple sclerosis (Houndmills, Basingstoke, England) 20201014 9

<h4>Background</h4>Defective alleles within the <i>PRF1</i> gene, encoding the pore-forming protein perforin, in combination with environmental factors, cause familial type 2 hemophagocytic lymphohistiocytosis (FHL2), a rare, severe autosomal recessive childhood disorder characterized by massive release of cytokines-cytokine storm.<h4>Objective</h4>The aim of this study was to determine the function of hypomorph <i>PRF1:p.A91V</i> g.72360387 G > A on multiple sclerosis (MS) and type 1 diabetes ( ...[more]

PMID: 33566725

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Dataset Information

PRF1 mutation alters immune system activation, inflammation, and risk of autoimmunity.

Background

Objective

Methods

Results

Conclusion

Publications

<i>PRF1</i> mutation alters immune system activation, inflammation, and risk of autoimmunity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

PRF1 mutation alters immune system activation, inflammation, and risk of autoimmunity.

Background

Objective

Methods

Results

Conclusion

Publications

&lt;i&gt;PRF1&lt;/i&gt; mutation alters immune system activation, inflammation, and risk of autoimmunity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

<i>PRF1</i> mutation alters immune system activation, inflammation, and risk of autoimmunity.