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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

262 Citations (Web of Science)


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.
Original languageEnglish
Pages (from-to)381-402
Issue number6
Publication statusPublished - Nov 2010

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