Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency

Bertrand Boisson; Emmanuel Laplantine; Carolina Prando; Silvia Giliani; Elisabeth Israelsson; Zhaohui Xu; Avinash Abhyankar; Laura Israël; Giraldina Trevejo-Nunez; Dusan Bogunovic; Alma-Martina Cepika; Donna Macduff; Maya Chrabieh; Marjorie Hubeau; Fanny Bajolle; Marianne Debré; Evelina Mazzolari; Donatella Vairo; Fabrice Agou; Herbert Virgin; Xavier Bossuyt; Caroline Rambaud; Fabio Facchetti; Damien Bonnet; Pierre Quartier; Jean-Christophe Fournet; Virginia Pascual; Damien Chaussabel; Luigi Notarangelo; Anne Puel; Alain Israël; Jean-Laurent Casanova; Capucine Picard

doi:10.1038/ni.2457

Journal articles

Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency

Bertrand Boisson ¹ Emmanuel Laplantine ² Carolina Prando ¹ Silvia Giliani ³ Elisabeth Israelsson ⁴ Zhaohui Xu ⁵ Avinash Abhyankar ¹ Laura Israël ⁶ Giraldina Trevejo-Nunez ¹ Dusan Bogunovic ¹ Alma-Martina Cepika ⁵ Donna Macduff ⁷ Maya Chrabieh ⁶ Marjorie Hubeau ⁶ Fanny Bajolle ⁸ Marianne Debré ⁸ Evelina Mazzolari ³ Donatella Vairo ³ Fabrice Agou ⁹ Herbert Virgin ⁷ Xavier Bossuyt ¹⁰ Caroline Rambaud ¹¹ Fabio Facchetti ³ Damien Bonnet ^{12, 8} Pierre Quartier ^{12, 8} Jean-Christophe Fournet ^{12, 8} Virginia Pascual ⁵ Damien Chaussabel ^{4, 5} Luigi Notarangelo ¹³ Anne Puel ⁶ Alain Israël ² Jean-Laurent Casanova ^{1, 6, 8, *} Capucine Picard ^{6, 8}

* Corresponding author

1 Rockefeller University [New York]

2 SMAC - Signalisation Moléculaire et Activation Cellulaire

3 Università degli Studi di Brescia [Brescia]

4 BRI - Benaroya Research Institute [Seattle]

5 BIIR - Baylor Institute for Immunology Research

6 Inserm U980 - Génétique Humaine des Maladies Infectieuses

7 Washington University School of Medicine in St. Louis

8 CHU Necker - Enfants Malades [AP-HP]

9 Biochimie Structurale et Cellulaire

10 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven

11 Hôpital Raymond Poincaré [AP-HP]

12 UPD5 - Université Paris Descartes - Paris 5

13 HMS - Harvard Medical School [Boston]

Abstract : We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic autoinflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1), a component of the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin 1β (IL-1β) was compromised in the patients' fibroblasts. By contrast, the patients' mononuclear leukocytes, particularly monocytes, were hyper-responsive to IL-1β. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1β responses thus differed between cell types, consistent with the unique association of autoinflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB–dependent IL-1β responses differently in different cell types.

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Journal articles

Domain :

Life Sciences [q-bio]

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Submitted on : Friday, July 2, 2021 - 4:23:05 PM
Last modification on : Tuesday, September 21, 2021 - 12:40:01 PM

Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency

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Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency

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