Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries.
Creators: name: Beaucoudrey, Ludovic De
name: Samarina, Arina
name: Bustamante, Jacinta
name: Cobat, Aurélie
name: Boisson-Dupuis, Stéphanie
name: Feinberg, Jacqueline
name: Al-Muhsen, Saleh
name: Jannière, Lucile
name: Rose, Yoann
name: Suremain, Maylis De
name: Kong, Xiao-Fei
name: Filipe-Santos, Orchidée
name: Chapgier, Ariane
name: Picard, Capucine
name: Fischer, Alain
name: Dogu, Figen
name: Ikinciogullari, Aydan
name: Tanir, Gonul
name: Al-Hajjar, Sami
name: Al-Jumaah, Suliman
name: Frayha, Husn H.
name: AlSum, Zobaida
name: Al-Ajaji, Sulaiman
name: Alangari, Abdullah
name: Haas, Walter
Publisher: name: Robert Koch-Institut, Infektionsepidemiologie
Year: 2010
Subjects: subject: Adolescent
subject: Humans
subject: Female
subject: Genotype
subject: Male
subject: Middle Aged
subject: Child
subject: Adult
subject: Infant
subject: Age Factors
subject: Survival Analysis
subject: Child Preschool
subject: Mycobacterium tuberculosis/isolation &amp; purification
subject: Infant Newborn
subject: Cytokines/blood
subject: Interleukin-12 Receptor beta 1 Subunit/deficiency
subject: Interleukin-12 Receptor beta 1 Subunit/genetics
subject: Mycobacterium Infections Nontuberculous/epidemiology
subject: Mycobacterium Infections Nontuberculous/genetics
subject: Mycobacterium bovis/isolation &amp; purification
subject: Nontuberculous Mycobacteria/isolation &amp; purification
subject: 610 Medizin

description: Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.