title: LRBA deficiency with autoimmunity and early onset chronic erosive polyarthritis.
abstract: LRBA (lipopolysaccharide-responsive and beige-like anchor protein) deficiency associates immune deficiency, lymphoproliferation, and various organ-specific autoimmunity. To date, prevalent symptoms are autoimmune cytopenias and enteropathy, and lymphocytic interstitial lung disease. In 2 siblings from a consanguineous family presenting with early onset polyautoimmunity, we presumed autosomal recessive inheritance and performed whole exome sequencing. We herein report the first case of early-onset, severe, chronic polyarthritis associated with LRBA deficiency. A novel 1bp insertion in the LRBA gene, abolishing protein expression, was identified in this family. Among the 2 brothers homozygous for LRBA mutation, one developed Evans syndrome and deceased at age 8.5 from complications of severe autoimmune thrombocytopenia. His brother, who carried the same homozygous LRBA mutation, early-onset erosive polyarthritis associated with chronic, bilateral, anterior uveitis and early onset type 1 diabetes mellitus. This report widens the clinical spectrum of LRBA deficiency and, in lights of the variable phenotypes described so far, prompts us to screen for this disease in patients with multiple autoimmune symptoms in the family, including severe, erosive, polyarticular juvenile arthritis.
authors.affiliation: INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric autoimmune Diseases, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Lévy
authors.affiliation: INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric autoimmune Diseases, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Stolzenberg
authors.affiliation: Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; Pathology Department, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France; INSERM UMR 1163, Laboratory of Molecular Mechanisms of Hematologic Disorders and Therapeutic Implications, 75015 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: Paediatric Radiology Department, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Breton
authors.affiliation: INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric autoimmune Diseases, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; Paediatric Immuno-haematology and Rheumatology Department, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Neven
authors.affiliation: Paediatric Department, Jean-Verdier Hospital, Assistance Publique - Hôpitaux de Paris, 93140 Bondy, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Sauvion
authors.affiliation: Genomic Platform, INSERM UMR 1163, Paris Descartes Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Zarhrate
authors.affiliation: Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; INSERM UMR 1163, Bioinformatics Department, Institute Imagine, 75015 Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Nitschké
authors.affiliation: Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; Paediatric Immuno-haematology and Rheumatology Department, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France; INSERM UMR 1163, Imagine Institute, 75015 Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.affiliation: INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric autoimmune Diseases, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Magérus-Chatinet
authors.affiliation: INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric autoimmune Diseases, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; Paediatric Immuno-haematology and Rheumatology Department, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
authors.affiliation: INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric autoimmune Diseases, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France. Electronic address: frederic.rieux-laucat@inserm.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rieux-Laucat
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D001168:Arthritis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics*; D002675:Child, Preschool; D002908:Chronic Disease; D003241:Consanguinity; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics / Q000378:metabolism; D059472:Exome / Q000235:genetics; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D035781:Siblings; D014606:Uveitis, Anterior / Q000150:complications / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C428703:LRBA protein, human
keywords: Autoimmunity; Exome sequencing; Juvenile idiopathic arthritis; LRBA deficiency; Primary immune deficiency