de Beaucoudrey Ludovic, Samarina Arina, Bustamante Jacinta, Cobat Aurélie, Boisson-Dupuis Stéphanie, Feinberg Jacqueline, Al-Muhsen Saleh, Jannière Lucile, Rose Yoann, de Suremain Maylis, Kong Xiao-Fei, Filipe-Santos Orchidée, Chapgier Ariane, Picard Capucine, Fischer Alain, Dogu Figen, Ikinciogullari Aydan, Tanir Gonul, Al-Hajjar Sami, Al-Jumaah Suliman, Frayha Husn H, AlSum Zobaida, Al-Ajaji Sulaiman, Alangari Abdullah, Al-Ghonaium Abdulaziz, Adimi Parisa, Mansouri Davood, Ben-Mustapha Imen, Yancoski Judith, Garty Ben-Zion, Rodriguez-Gallego Carlos, Caragol Isabel, Kutukculer Necil, Kumararatne Dinakantha S, Patel Smita, Doffinger Rainer, Exley Andrew, Jeppsson Olle, Reichenbach Janine, Nadal David, Boyko Yaryna, Pietrucha Barbara, Anderson Suzanne, Levin Michael, Schandené Liliane, Schepers Kinda, Efira André, Mascart Françoise, Matsuoka Masao, Sakai Tatsunori, Siegrist Claire-Anne, Frecerova Klara, Blüetters-Sawatzki Renate, Bernhöft Jutta, Freihorst Joachim, Baumann Ulrich, Richter Darko, Haerynck Filomeen, De Baets Frans, Novelli Vas, Lammas David, Vermylen Christiane, Tuerlinckx David, Nieuwhof Chris, Pac Malgorzata, Haas Walther H, Müller-Fleckenstein Ingrid, Fleckenstein Bernhard, Levy Jacob, Raj Revathi, Cohen Aileen Cleary, Lewis David B, Holland Steven M, Yang Kuender D, Wang Xiaochuan, Wang Xiaohong, Jiang Liping, Yang Xiqiang, Zhu Chaomin, Xie Yuanyuan, Lee Pamela Pui Wah, Chan Koon Wing, Chen Tong-Xin, Castro Gabriela, Natera Ivelisse, Codoceo Ana, King Alejandra, Bezrodnik Liliana, Di Giovani Daniela, Gaillard Maria Isabel, de Moraes-Vasconcelos Dewton, Grumach Anete Sevciovic, da Silva Duarte Alberto Jose, Aldana Ruth, Espinosa-Rosales Francisco Javier, Bejaoui Mohammed, Bousfiha Ahmed Aziz, Baghdadi Jamila El, Özbek Namik, Aksu Guzide, Keser Melike, Somer Ayper, Hatipoglu Nevin, Aydogmus Çigdem, Asilsoy Suna, Camcioglu Yildiz, Gülle Saniye, Ozgur Tuba T, Ozen Meteran, Oleastro Matias, Bernasconi Andrea, Mamishi Setareh, Parvaneh Nima, Rosenzweig Sergio, Barbouche Ridha, Pedraza Sigifredo, Lau Yu Lung, Ehlayel Mohammad S, Fieschi Claire, Abel Laurent, Sanal Ozden, Casanova Jean-Laurent
From Laboratory of Human Genetics of Infectious Diseases U980 (LDB, A. Samarina, J. Bustamante, A. Cobat, SBD, J. Feinberg, L. Jannière, YR, MDS, XFK, OFS, A. Chapgier, CP, LA, JLC) and Laboratory of Normal and Pathologic Development of the Immune System U768 (AF), Institut National de la Santé et de la Recherche Médicale, Paris, France; University Paris Descartes (LDB, A. Samarina, J. Bustamante, A. Cobat, SBD, J. Feinberg, L. Jannière, YR, MDS, XFK, OFS, A. Chapgier, CP, AF, LA, JLC), Necker Medical School, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases (A. Samarina, SBD, XFK, LA, JLC), The Rockefeller University, New York, New York; Prince Naif Center for Immunology Research (SAM, SAH, ZAS, AA, JLC) and Department of Pediatrics (SAM, ZAS, AA), College of Medicine, King Saud University, Riyadh, Saudi Arabia; Department of Pediatrics (SAM, SAH, SAJ, HHF, AAG), King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; Study Center of Primary Immunodeficiencies (CP) and Pediatric Hematology-Immunology Unit (AF, JLC), Necker Hospital, AP-HP, Paris, France; Department of Pediatric Allergy and Immunology (FD, AI), Ankara University School of Medicine, Ankara, Turkey; Dr Sami Ulus Children Health and Diseases Training and Research Center (GT), Ankara, Turkey; Department of Pediatrics (SAA), King Abdulaziz Medical City, King Fahad National Guard Hospital, Riyadh, Saudi Arabia; Division of Infectious Diseases and Clinical Immunology (PA, DM), National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Teheran, Iran; Laboratory of Cytoimmunology (IBM, RB), Pasteur Institut of Tunis, Tunis-Belvédère, Tunisia; Department of Immunology (JY, M. Oleastro, AB), Juan-Pedro Garrahan National Hospital of Pediatrics, Buenos Aires, Argentina; Department of Pediatrics (BZG), Schneider Children's Medical Center of Israel, Petah Tiqva, Israel; Department of Immunology (CRG), Gran Canaria Dr Negrin University Hospital, Las Palmas de Gran Canaria, Spain; Laboratory of Immunology (IC), Vall d'Hebron Hospital, Barcelona, Spain; Department of Pediatrics (NK, GA), Ege University Medical School, Izmir, Turkey; Department of Clinical Biochemistry and Immunology (DSK, S. Patel, RD), Addenbrookes Hospital, Cambridge, United Kingdom; Immunology Laboratory and Respiratory Infection, Inflammation and Immunology Unit, Departments of Pathology and Thoracic Medicine (A. Exley), Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom; Astrid Lindgren Childrens Hospital Karolinska University Hospital (OJ), Huddinge, Sweden; Department of Immunology (JR) and Department of Infectious Diseases (DN), University Children's Hospital of Zurich, Zurich, Switzerland; Lviv Regional Specialized Children's Hospital (YB), Lviv, Ukraine; Department of Immunology (BP, MP), Children's Memorial Health Institute, Warsaw, Poland; Department of Pediatrics (S. Anderson, ML), Imperial College School of Medicine, St Mary's Hospital, London, United Kingdom; Immunobiology Clinic (LS, A. Efira, FM) and Immunodeficiency Department (KS), Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Laboratory of Vaccinology and Mucosal Immunity (FM), Université Libre de Bruxelles, Brussels, Belgium; Laboratory of Virus Control (MM), Institute for Virus Research, Kyoto University, Kyoto, Japan; Department of Internal Medicine (TS), National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan; Department of Pediatrics (CAS), University of Geneva, Geneva, Switzerland; Department of International Relations (KF), Ministry of Health, Bratislava, Slovak Republic; Department of Pediatric Hematology and Oncology (RBS), Giessen, Germany; Department of Pediatric Pulmonology and Neonatology (J. Bernhöft), Hannover Medical School, Hannover, Germany; Department of Pediatrics (J. Freihorst, UB), University Hospital Center-Rebro, Zagreb, Croatia; Department of Pediatric Pulmonology and Immunology (FH, FDB), University Hospital Ghent, Ghent, Belgium; Infectious Diseases Unit (VN), Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom; MRC Center for Immune Regulation (DL), The Medical School, University of Birmingham, Birmingham, United Kingdom; Department of Pediatric Hematology and Oncology (CV), Cliniques Universitaires Saint Luc et Université Catholique de Louvain, Brussels, Belgium; Department of Pediatrics (DT), Mont-Godinne Clinics, Université Catholique de Louvain, Brussels, Belgium; Department of Internal Medicine/Division of Clinical and Experimental Immunology (CN), Maastricht University Medical Centre, Maastricht, The Netherlands; Unit for Respiratory Infections, Department of Infectious Disease Epidemiology (WHH), Robert Koch Institute, Berlin, Germany; Institut für Klinische und Molekulare Virologie (IMF, BF), Universität Erlangen-Nürnberg, Germany; Pediatric Department (JL), Soroka Medical Center, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel; Department of Pediatric Hematology (RR), Apollo Speciality Hospitals, Chennai, India; Department of Pediatrics (ACC, DBL), Stanford University School of Medicine, Stanford, California; Laboratory of Clinical Infectious Diseases (SMH) and Infectious Diseases Susceptibility Unit, Laboratory of Host Defenses (SR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Department of Pediatric Allergy (KDY), Immunology and Rheumatology and Department of Medical Research, Chang Gung Children's Hospital, and Chang Gung University, Kaohsiung, Taiwan; Department of Clinical Immunology (Xiaochuan Wang), Children's Hospital of Fudan University, Shanghai, China; Clinical Immunology Laboratory (Xiqiang Yang), Children's Hospital of Chongqing Medical University, Chongqing, China; Department of Paediatrics and Adolescent Medicine (PPWL, KWC, YLL), Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China; Department of Pediatrics (TXC), Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Immunology (GC), Federal University of Bahia, Brazil; University Hospital of Caracas (IN), Caracas, Venezuela; Luis Calvo Mackenna Hospital (A. Codoceo, AK), Santiago, Chile; Department of Immunology (LB, DDG, MIG), Ricardo Gutiérrez Children Hospital, Buenos Aires, Argentina; Laboratory of Investigation in Dermatology and Immunodeficiencies, Department of Dermatology (DDMV, ASG, AJDSD), University of São Paulo Medical School, São Paulo, Brazil; Department of Pulmonology (RA), Children's Hospital Federico Gomez, Mexico City, Mexico; Department of Immunology (FJER), National Institute of Pediatrics, Mexico City, Mexico; National Center of Bone Marrow Graft (MB), Tunis, Tunisia; Clinical Immunology Unit (AAB), Ibn-Rochd Hospital, Casablanca, Morocco; Laboratory of Immunology (JEB), Military Hospital Mohamed V, Hay Riad Rabat, Morocco; Department of Pediatrics (NÖ), Baskent University School of Medicine, Ankara, Turkey; Department of Pediatric Infectious Diseases and Clinical Immunology (MK, A. Somer), Istanbul University Faculty of Medicine, Istanbul, Turkey; Department of Pediatric Infectious Diseases and Immunology (NH, CA), Bakirkoy Maternity and Children's State Hospital, Istanbul, Turkey; Department of Pediatrics (S. Asilsoy, SG), Dr Behçet Uz Children Research and Training Hospital,Izmir, Turkey; Department of Pediatrics, Infectious Diseases, Clinical Immunology and Allergy Division (YC), Cerrahpaşa Medical School, Istanbul University, Cerrahpaşa, Istanbul, Turkey; Immunology Division (TTO, OS), Hacettepe University Children's Hospital, Ankara, Turkey; Division of Pediatric Infectious Disease (M. Ozen), Faculty of Medicine, Inonu University, Malatya, Turkey; Department of Pediatrics (SM, NP), Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Biochemistry (S. Pedraza), INCMNSZ, Ministry of Health, Mexico City, Mexico; Section of Allergy-Immunology, Department of Pediatrics (MSE), Hamad Medical Corporation, Doha, Qatar; and Adult Immunopathology Unit (CF), Saint-Louis Hospital, AP-HP, Paris, France.
Medicine (Baltimore). 2010 Nov;89(6):381-402. doi: 10.1097/MD.0b013e3181fdd832.
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.
白细胞介素-12受体β1（IL-12Rβ1）缺陷是孟德尔遗传性分枝杆菌病易感性（MSMD）最常见的形式。我们对来自30个国家102个家族的141例患者进行了一项国际调查。在102例先证者中，首次感染的平均年龄为2.4岁。在78例患者中，感染由卡介苗（BCG；n = 65）、环境分枝杆菌（EM；也称为非典型或非结核分枝杆菌）（n = 9）或结核分枝杆菌（n = 4）引起。其余24例先证者中有22例最初表现为非伤寒性肠外沙门氏菌病。29例受基因影响的同胞中有20例出现临床症状（69%）；然而，8例仍无症状（27%）。9例有症状但未进行基因分型的同胞死亡。15例诊断为卡介苗反复感染，3例为环境分枝杆菌反复感染，22例为沙门氏菌病反复感染。132例有症状的患者中有90例感染单一微生物。40例诊断为多重感染，36例为分枝杆菌病和沙门氏菌病合并感染。卡介苗病对随后的环境分枝杆菌病有很强的保护作用（p = 0.00008）。还发生了各种其他传染病，尽管每种都很少见，但33例患者（23%）报告有念珠菌病。99例患者（70%）存活，最后一次随访的平均年龄为12.7岁±9.8岁（范围，0.5 - 46.4岁）。IL-12Rβ1缺陷的特征为儿童期发病的分枝杆菌病和沙门氏菌病、分枝杆菌病罕见复发以及沙门氏菌病更频繁复发。该疾病的临床外显率更高、对感染的易感性更广泛且预后比以前认为的更差。
