Revisiting Human IL-12R[beta]1 Deficiency: A Survey of 141 Patients From 30 Countries.
de Beaucoudrey, Ludovic PhD*; Samarina, Arina MD*; Bustamante, Jacinta MD, PhD*; Cobat, Aurelie MD, PhD*; Boisson-Dupuis, Stephanie PhD*; Feinberg, Jacqueline PhD*; Al-Muhsen, Saleh MD; Janniere, Lucile MS; Rose, Yoann MS; de Suremain, Maylis MS; Kong, Xiao-Fei MD, PhD; Filipe-Santos, Orchidee PhD; Chapgier, Ariane PhD; Picard, Capucine MD, PhD; Fischer, Alain MD, PhD; Dogu, Figen MD; Ikinciogullari, Aydan MD; Tanir, Gonul MD; Al-Hajjar, Sami MD; Al-Jumaah, Suliman MD; Frayha, Husn H. MD; AlSum, Zobaida MD; Al-Ajaji, Sulaiman MD; Alangari, Abdullah MD; Al-Ghonaium, Abdulaziz MD; Adimi, Parisa MS; Mansouri, Davood MD; Ben-Mustapha, Imen MD; Yancoski, Judith PhD; Garty, Ben-Zion MD; Rodriguez-Gallego, Carlos PhD; Caragol, Isabel MD, PhD; Kutukculer, Necil MD; Kumararatne, Dinakantha S. MD, PhD; Patel, Smita MD, PhD; Doffinger, Rainer PhD; Exley, Andrew MD; Jeppsson, Olle MD; Reichenbach, Janine MD; Nadal, David MD; Boyko, Yaryna PhD; Pietrucha, Barbara MD, PhD; Anderson, Suzanne MD, PhD; Levin, Michael MD, PhD; Schandene, Liliane PhD; Schepers, Kinda MD; Efira, Andre MS; Mascart, Francoise MD, PhD; Matsuoka, Masao MD, PhD; Sakai, Tatsunori MD, PhD; Siegrist, Claire-Anne MD; Frecerova, Klara MD; Bluetters-Sawatzki, Renate MD, PhD; Bernhoft, Jutta MD; Freihorst, Joachim MD; Baumann, Ulrich MD, PhD; Richter, Darko MD, PhD; Haerynck, Filomeen MD; De Baets, Frans MD, PhD; Novelli, Vas MD; Lammas, David PhD; Vermylen, Christiane MD, PhD; Tuerlinckx, David MD; Nieuwhof, Chris MD, PhD; Pac, Malgorzata MD, PhD; Haas, Walther H. MD, PhD; Muller-Fleckenstein, Ingrid MS; Fleckenstein, Bernhard MD; Levy, Jacob MD; Raj, Revathi MD; Cohen, Aileen Cleary MD, PhD; Lewis, David B. MD; Holland, Steven M. MD; Yang, Kuender D. MD, PhD; Wang, Xiaochuan MD, PhD; Wang, Xiaohong; Jiang, Liping MD; Yang, Xiqiang MD; Zhu, Chaomin MD; Xie, Yuanyuan MD; Lee, Pamela Pui Wah MD, PhD; Chan, Koon Wing; Chen, Tong-Xin MD, PhD; Castro, Gabriela MD; Natera, Ivelisse MD; Codoceo, Ana MD; King, Alejandra MD; Bezrodnik, Liliana MD; Di Giovani, Daniela MD; Gaillard, Maria Isabel MS; de Moraes-Vasconcelos, Dewton MD, PhD; Grumach, Anete Sevciovic MD, PhD; da Silva Duarte, Alberto Jose MD, PhD; Aldana, Ruth MD; Espinosa-Rosales, Francisco Javier MD; Bejaoui, Mohammed MD; Bousfiha, Ahmed Aziz MD; Baghdadi, Jamila El PhD; Ozbek, Namik MD; Aksu, Guzide MD; Keser, Melike MD; Somer, Ayper MD; Hatipoglu, Nevin MD; Aydogmus, Cigdem MD; Asilsoy, Suna MD; Camcioglu, Yildiz MD; Gulle, Saniye MD; Ozgur, Tuba T. MD; Ozen, Meteran MD; Oleastro, Matias MD; Bernasconi, Andrea PhD; Mamishi, Setareh MD; Parvaneh, Nima MD; Rosenzweig, Sergio MD, PhD; Barbouche, Ridha MD, PhD; Pedraza, Sigifredo PhD; Lau, Yu Lung MD; Ehlayel, Mohammad S. MD; Fieschi, Claire MD, PhD; Abel, Laurent MD, PhD+; Sanal, Ozden MD+; Casanova, Jean-Laurent MD, PhD+
89(6):381-402, November 2010.
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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.
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