title: Combined IL-12 receptor and IgA deficiency in an adult man intestinally infested by an unknown, non-cultivable mycobacterium.
abstract: Interleukin-12 receptor deficiency is a well-described cause of human susceptibility to infection with low-virulent mycobacteria and Salmonella species. We identified a male patient presenting in his late forties with severe gastroenteropathy because of outbred infestation by a previously unknown mycobacterium. In addition to selective IgA deficiency, the patient was found to carry a not previously described R283X homozygous mutation in his IL12RΒ1 gene. Two of his sisters, a brother, and his four children were healthy, heterozygous carriers of the mutation. In this patient, the combination of two deficiencies could promote illness. Even though the IgA deficiency in itself does not predispose to mycobacterial disease, the lack of secreted IgA may have disturbed the intestinal homoeostasis and increased the susceptibility to the low-virulent mycobacterium that the patient was not able to clear because of his IL12R deficiency. Antimycobacterial chemotherapy and interferon-γ treatment for 2 years significantly improved his condition. This is the first description of IL12RΒ1 deficiency combined with another immunodeficiency, and we suggest that combinatory defects may circumvent the otherwise low penetrance of IL12RB1 deficiency.
authors.affiliation: Department of Clinical Immunology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Schejbel
authors.forename: E M
authors.initials: EM
authors.lastname: Rasmussen
authors.forename: H B
authors.initials: HB
authors.lastname: Kemp
authors.forename: A-C
authors.initials: AC
authors.lastname: Lundstedt
authors.forename: K R
authors.initials: KR
authors.lastname: Nielsen
authors.forename: N
authors.initials: N
authors.lastname: Obel
authors.forename: H
authors.initials: H
authors.lastname: Marquart
authors.forename: A B
authors.initials: AB
authors.lastname: Andersen
mesh_terms: D001483:Base Sequence; D001706:Biopsy; D005260:Female; D006801:Humans; D017098:IgA Deficiency / Q000150:complications / Q000276:immunology*; D007371:Interferon-gamma / Q000627:therapeutic use; D007410:Intestinal Diseases / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009161:Mycobacterium / Q000235:genetics; D009164:Mycobacterium Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D053707:Receptors, Interleukin-12 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment
chemical_list: D053707:Receptors, Interleukin-12; D007371:Interferon-gamma