Research Papers: Immunology:

Reduced serpinB9-mediated caspase-1 inhibition can contribute to autoinflammatory disease

Robert van der Burgh, Jan Meeldijk, Lieneke Jongeneel, Joost Frenkel, Niels Bovenschen, Mariëlle van Gijn and Marianne Boes _

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Oncotarget. 2016; 7:19265-19271. https://doi.org/10.18632/oncotarget.8086

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Robert van der Burgh1,5, Jan Meeldijk2,5, Lieneke Jongeneel1,5, Joost Frenkel3, Niels Bovenschen2,5, Mariëlle van Gijn4,* and Marianne Boes1,5,*

1 Department of Pediatric Immunology, Wilhelmina Children’s Hospital, UMC Utrecht, EA, Utrecht, Netherlands

2 Department of Pathology, University Medical Center Utrecht, CX, Utrecht, Netherlands

3 Department of General Pediatrics, Wilhelmina Children’s Hospital, UMC Utrecht, EA, Utrecht, Netherlands

4 Department of Genetics, University Medical Center Utrecht, EA, Utrecht, Netherlands

5 Laboratory of Translational Immunology, University Medical Center Utrecht, CX, Utrecht, Netherlands

* These authors have contributed equally to this work

Correspondence to:

Marianne Boes, email:

Keywords: serpinB9, autoinflammation, caspase-1, interleukin 1β, granzyme B, Immunology and Microbiology Section, Immune response, Immunity

Received: February 14, 2016 Accepted: February 23, 2016 Published: March 15, 2016


Patients who suffer from autoinflammatory disease (AID) exhibit seemingly uncontrolled release of interleukin (IL)-1β. The presence of this inflammatory cytokine triggers immune activation in absence of pathogens and foreign material. The mechanisms that contribute to ‘sterile inflammation’ episodes in AID patients are not fully understood, although for some AIDs underlying genetic causes have been identified. We show that the serine protease inhibitor B9 (serpinB9) regulates IL-1β release in human monocytes. SerpinB9 function is more commonly known for its role in control of granzyme B. SerpinB9 however also serves to restrain IL-1β maturation through caspase-1 inhibition. We here describe an autoinflammatory disease-associated serpinB9 (c.985G>T, A329S) variant, which we discovered in a patient with unknown AID. Using patient cells and serpinB9 overexpressing monocytic cells, we show the A329S variant of serpinB9 exhibits unobstructed granzyme B inhibition, but compromised caspase-1 inhibition. SerpinB9 gene variants might contribute to AID development.

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PII: 8086