Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα).


Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
17 Sep 2021
Historique:
entrez: 17 9 2021
pubmed: 18 9 2021
medline: 1 3 2022
Statut: ppublish

Résumé

Inhibitor of nuclear factor kappa B kinase alpha (IKKα) is critical for p100/NF-κB2 phosphorylation and processing into p52 and activation of the noncanonical NF-κB pathway. A patient with recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine and liver was found to have a homozygous p.Y580C mutation in the helix-loop-helix domain of IKKα. The mutation preserves IKKα kinase activity but abolishes the interaction of IKKα with its activator NF-κB–inducing kinase and impairs lymphotoxin-β–driven p100/NF-κB2 processing and

Identifiants

pubmed: 34533979
doi: 10.1126/sciimmunol.abf6723
pmc: PMC8930078
mid: NIHMS1787196
doi:

Substances chimiques

CHUK protein, human EC 2.7.11.10
I-kappa B Kinase EC 2.7.11.10

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabf6723

Subventions

Organisme : NIAID NIH HHS
ID : K08 AI116979
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI139633
Pays : United States

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Auteurs

Wayne Bainter (W)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Vassilios Lougaris (V)

Pediatrics Clinic, Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy.

Jacqueline G Wallace (JG)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Yousef Badran (Y)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Rodrigo Hoyos-Bachiloglu (R)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Zachary Peters (Z)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Hazel Wilkie (H)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Mrinmoy Das (M)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Erin Janssen (E)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Abdallah Beano (A)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Khaoula Ben Farhat (KB)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Christy Kam (C)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Luisa Bercich (L)

Department of Pathology, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.

Paolo Incardona (P)

Department of Pathology, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.

Vincenzo Villanacci (V)

Department of Pathology, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.

Maria Pia Bondioni (MP)

Department of Pediatric Radiology, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.

Antonella Meini (A)

Pediatrics Clinic, Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy.

Manuela Baronio (M)

Pediatrics Clinic, Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy.

Phammela Abarzua (P)

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Silvia Parolini (S)

Pediatrics Clinic, Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy.

Giovanna Tabellini (G)

Pediatrics Clinic, Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy.

Stefano Maio (S)

Department of Paediatrics, the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

Birgitta Schmidt (B)

Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Jeffrey D Goldsmith (JD)

Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

George Murphy (G)

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Georg Hollander (G)

Department of Paediatrics, the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Paediatric Immunology, Department of Biomedicine, University of Basel, University Children's Hospital Basel, Basel, Switzerland.
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.

Alessandro Plebani (A)

Pediatrics Clinic, Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy.

Janet Chou (J)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Raif S Geha (RS)

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

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