Andrés Augusto Arias1,2, Carlos M Perez-Velez1,3,4, Julio César Orrego1, Marcela Moncada-Velez1, Jessica Lineth Rojas1, Alejandra Wilches5,6, Andrea Restrepo7,8, Mónica Trujillo7, Carlos Garcés6,7, Catalina Arango-Ferreira1,5,6, Natalia González9,10, Carmen Oleaga-Quintas11,12, Diana Fernández1, Johana Marcela Isaza-Correa1, Diego Eduardo Gongóra1, Daniel Gonzalez-Loaiza1, Juan Esteban Sierra6, Jean Laurent Casanova11,12,13,14,15, Jacinta Bustamante11,12,15,16, José Luis Franco17. 1. Grupo de Inmunodeficiencias Primarias, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No, 52-21, Medellín, Colombia. 2. Escuela de Microbiología, Universidad de Antioquia UdeA, Calle 70 No, 52-21, Medellín, Colombia. 3. Tuberculosis Clinic, Pima County Health Department, Tucson, USA. 4. Division of Infectious Diseases, University of Arizona College of Medicine, Tucson, USA. 5. Hospital Universitario San Vicente Fundación, Medellin, Colombia. 6. Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No, 52-21, Medellín, Colombia. 7. Departamento de Pediatría, Hospital Pablo Tobon Uribe, Medellin, Colombia. 8. Clínica Universitaria Bolivariana, Medellin, Colombia. 9. Hospital Infantil Rafael Henao Toro, Manizales, Colombia. 10. Fundación Universitaria de las Américas, Pereira, Colombia. 11. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France. 12. Paris Descartes University, Imagine Institute, Paris, France. 13. Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France. 14. Howard Hughes Medical Institute, New York, USA. 15. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller branch, The Rockefeller University, New York, NY, USA. 16. Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France. 17. Grupo de Inmunodeficiencias Primarias, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No, 52-21, Medellín, Colombia. jose.franco@udea.edu.co.
Abstract
PURPOSE: Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. METHODS: We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rβ1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. CONCLUSIONS: To our knowledge, this is the third patient with MSMD due to IL-12Rβ1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.
PURPOSE: Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. METHODS: We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rβ1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. CONCLUSIONS: To our knowledge, this is the third patient with MSMD due to IL-12Rβ1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.
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