Revisiting Human IL-12R beta 1 Deficiency A Survey of 141 Patients From 30 Countries

Ludovic De Beaucoudrey (1, 2) , Arina Samarina (3, 1, 2) , Jacinta Bustamante (1, 2) , Aurélie Cobat (1, 2) , Stephanie Boisson-Dupuis (1, 2, 3) , Jacqueline Feinberg (1, 2) , Saleh Al-Muhsen (4, 5, 6) , Lucile Janniere (1, 2) , Yoann Rose (1, 2) , Maylis De Suremain (1, 2) , Xiao-Fei Kong (1, 2, 3) , Orchidée Filipe-Santos (1, 2) , Ariane Chapgier (1, 2) , Capucine Picard (1, 7, 2) , Alain Fischer (8, 7, 9, 2) , Figen Dogu (10) , Aydan Ikinciogullari (10) , Gonul Tanir (10) , Sami Al-Hajjar (4, 6) , Suliman Al-Jumaah (6) , Husn H. Frayha (6) , Zobaida Alsum , Sulaiman Al-Ajaji (11) , Abdullah Alangari (4, 5) , Abdulaziz Al-Ghonaium (6) , Parisa Adimi (12) , Davood Mansouri (12) , Imen Ben-Mustapha (13) , Judith Yancoski (14) , Ben-Zion Garty (15) , Carlos Rodriguez-Gallego (16) , Isabel Caragol (17) , Necil Kutukculer (18) , Dinakantha S. Kumararatne (19) , Smita Patel (19) , Rainer Döffinger (19) , Andrew Exley (20, 21) , Olle Jeppsson (22) , Janine Reichenbach (23) , David Nadal (24) , Yaryna Boyko (25) , Suzanne Anderson (26) , Barbara Pietrucha (27) , Michael Levin (26) , Liliane Schandene (28) , Kinda Schepers (29) , Andre Efira (28) , Francoise Mascart (28, 30) , Tatsunori Sakai (31) , Masao Matsuoka (32) , Claire-Anne Siegrist (33) , Klara Frecerova (34) , Renate Blueetters-Sawatzki (35) , Jutta Bernhoeft (36) , Joachim Freihorst (37) , Ulrich Baumann (37) , Darko Richter , Filomeen Haerynck (38) , Frans de Baets (38) , Vas Novelli (39) , David Lammas (40) , Christiane Vermylen (41) , David Tuerlinckx (42) , Chris Nieuwhof (43) , Malgorzata Pac (27) , Walther H. Haas (44) , Ingrid Mueller-Fleckenstein (45) , Bernhard Fleckenstein (45) , Jacob Levy (46) , Aileen Cleary Cohen (47) , David B. Lewis (47) , Steven M. Holland (48) , Kuender D. Yang (49) , Xiaochuan Wang (50) , Xiaohong Wang , Revathi Raj , Liping Jiang , Xiqiang Yang (51) , Chaomin Zhu , Yuanyuan Xie , Pamela Pui Wah Lee (52) , Koon Wing Chan (52) , Gabriela Castro (53) , Tong-Xin Chen (54) , Ivelisse Natera (55) , Ana Codoceo (56) , Alejandra King (56) , Liliana Bezrodnik (57) , Daniela Di Giovani (57) , Maria Isabel Gaillard (57) , Dewton De Moraes-Vasconcelos (58) , Anete Sevciovic Grumach (58) , Alberto Jose Da Silva Duarte (58) , Ruth Aldana (59) , Francisco Javier Espinosa-Rosales (60) , Mohammed Bejaoui (61) , Ahmed Aziz Bousfiha (62) , Jamila El Baghdadi (63) , Namik Ozbek (64) , Guzide Aksu (18) , Melike Keser (65) , Ayper Somer (65) , Nevin Hatipoglu (66) , Cigdem Aydogmus (66) , Suna Asilsoy (67) , Yildiz Camcioglu (68) , Saniye Gulle (67) , Tuba T. Ozgur (69) , Meteran Ozen (70) , Matias Oleastro (48) , Andrea Bernasconi (48) , Setareh Mamishi (71) , Nima Parvaneh (71) , Sergio Rosenzweig (48) , Sigifredo Pedraza (72) , Mohamed-Ridha Barbouche (13) , Yu Lung Lau (73) , Mohammad S. Ehlayel (74) , Claire Fieschi (1, 75) , Laurent Abel (1, 2, 3) , Ozden Sanal (69) , Jean-Laurent Casanova (1, 76)

1 Inserm U980 - Génétique Humaine des Maladies Infectieuses
2 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
3 St. Giles Laboratory of Human Genetics of Infectious Diseases
4 Department of Pediatrics
5 Coll Med, Prince Naif Ctr Immunol Res
6 Coll Med, Dept Pediat
7 IRNEM - IFR Necker-Enfants Malades
8 Developpement Normal et Pathologique du Système Immunitaire
9 Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique
10 Sami Ulus Children Hlth & Dis Training & Res Ctr, Ankara
11 Dept Pediat
12 SBUMS - Shahid Beheshti University of Medical Sciences [Tehran]
13 Laboratoire d'immunologie clinique [Institut Pasteur de Tunis]
14 Dept Immunol
15 Dept Pediat
16 Dept Immunol
17 Immunol Lab
18 Department of Pediatrics
19 Dept Clin Biochem & Immunol
20 Inflammat & Immunol Unit, Dept Pathol
21 Inflammat & Immunol Unit, Dept Thorac Med
22 Karolinska University Hospital [Stockholm]
23 Dept Immunol
24 Dept Infect Dis
25 Lviv Reg Specialized Childrens Hosp
26 Dept Pediat
27 Dept Immunol
28 Immunobiol Clin, Hop Erasme
29 Immunodeficiency Dept, Hop Erasme
30 Lab Vaccinol & Mucosal Immun
31 Dept Internal Med
32 Laboratory of Virus Control
33 Dept Pediat
34 Dept Int Relat
35 Dept Pediat Hematol & Oncol
36 Dept Pediat Pulmonol & Neonatol
37 Dept Pediat
38 Dept Pediat Pulmonol & Immunol
39 Infect Dis Unit
40 Ctr Immune Regulat
41 Dept Pediat Hematol & Oncol
42 Dept Pediat, Mt Godinne Clin
43 Dept Internal Med, Div Clin & Expt Immunol
44 Dept Infect Dis Epidemiol, Unit Resp Infect
45 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg
46 Pediatric Department,
47 Dept Pediat
48 Lab Clin Infect Dis
49 Dept Pediat Allergy
50 Dept Clin Immunol
51 Clin Immunol Lab
52 Dept Paediat & Adolescent Med
53 Dept Immunol
54 Dept Pediat,Sch Med
55 Univ Hosp Caracas
56 Hosp Ninos Luis Calvo Mackenna
57 Dept Immunol
58 Dept Dermatol, Lab Invest Dermatol & Immunodeficiencies
59 Dept Pulmonol
60 Dept Immunol
61 Natl Ctr Bone Marrow Graft, Tunis
62 Clinical Immunology Unit
63 Genetics Unit
64 Dept Pediat
65 Dept Pediat Infect Dis & Clin Immunol
66 Dept Pediat Infect Dis & Immunol
67 Dept Pediat
68 Department of Pediatrics, Infectious Diseases
69 Hacettepe University = Hacettepe Üniversitesi
70 Fac Med Malatya
71 TUMS - Tehran University of Medical Sciences
72 Dept Biochem
73 Department of Pediatric and Adolescent Medicine
74 Hamad medical corporation
75 Laboratoire d'immunologie
76 Service d'immuno-hématologie pédiatrique [CHU Necker]

Interleukin-12 receptor beta 1 (IL-12R beta 1) 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-Guerin (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-12R beta 1 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.

Domains: Life Sciences [q-bio]

Ludovic De Beaucoudrey, Arina Samarina, Jacinta Bustamante, Aurélie Cobat, Stephanie Boisson-Dupuis, et al.. Revisiting Human IL-12R beta 1 Deficiency A Survey of 141 Patients From 30 Countries. Medicine, 2010, 89 (6), pp.381-402. ⟨10.1097/MD.0b013e3181fdd832⟩. ⟨pasteur-01375300⟩