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Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency

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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.

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Acknowledgments

We thank Yelena Nemirovskaya, Carolyn Álvarez, and Lahouari Amar for their administrative support and Claudia Llerena of the National Institute of Health in Bogotá (Colombia) for her assistance with microbiological analyses. This research was funded by the Colombian Administrative Department of Science, Technology and Innovation Colciencias (contract: 111556934990), Colciencias-ECOS NORD (contract: 619-2013), Group of Primary Immunodeficiencies and Fundación Diana García de Olarte para las Inmunodeficiencias Primarias-FIP-(Colombia), the National Institute of Allergy and Infectious Diseases grant number 5R01AI089970, the National Center for Research Resources and the National Center for Advancing Sciences of the National Institutes of Health grant number 8UL1TR000043, The Rockefeller University, the St. Giles Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris Descartes University, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID), and the French National Research Agency (ANR-GENMSMD ANR-16-CE17-0005-01 for JB) under the “Investments for the future” (grand number ANR-10-IAHU-01).

Author information

Author notes

  1. Natalia González

    Present address: Fundación Universitaria de las Américas, Pereira, Colombia

  2. Andrés Augusto Arias and Carlos M. Perez-Velez, Jacinta Bustamante, and José Luis Franco contributed equally to this work

Authors and Affiliations

  1. Grupo de Inmunodeficiencias Primarias, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No, 52-21, Medellín, Colombia

    Andrés Augusto Arias, Carlos M. Perez-Velez, Julio César Orrego, Marcela Moncada-Velez, Jessica Lineth Rojas, Catalina Arango-Ferreira, Diana Fernández, Johana Marcela Isaza-Correa, Diego Eduardo Gongóra, Daniel Gonzalez-Loaiza & José Luis Franco

  2. Escuela de Microbiología, Universidad de Antioquia UdeA, Calle 70 No, 52-21, Medellín, Colombia

    Andrés Augusto Arias

  3. Tuberculosis Clinic, Pima County Health Department, Tucson, USA

    Carlos M. Perez-Velez

  4. Division of Infectious Diseases, University of Arizona College of Medicine, Tucson, USA

    Carlos M. Perez-Velez

  5. Hospital Universitario San Vicente Fundación, Medellin, Colombia

    Alejandra Wilches & Catalina Arango-Ferreira

  6. Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No, 52-21, Medellín, Colombia

    Alejandra Wilches, Carlos Garcés, Catalina Arango-Ferreira & Juan Esteban Sierra

  7. Departamento de Pediatría, Hospital Pablo Tobon Uribe, Medellin, Colombia

    Andrea Restrepo, Mónica Trujillo & Carlos Garcés

  8. Clínica Universitaria Bolivariana, Medellin, Colombia

    Andrea Restrepo

  9. Hospital Infantil Rafael Henao Toro, Manizales, Colombia

    Natalia González

  10. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France

    Carmen Oleaga-Quintas, Jean Laurent Casanova & Jacinta Bustamante

  11. Paris Descartes University, Imagine Institute, Paris, France

    Carmen Oleaga-Quintas, Jean Laurent Casanova & Jacinta Bustamante

  12. Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France

    Jean Laurent Casanova

  13. Howard Hughes Medical Institute, New York, USA

    Jean Laurent Casanova

  14. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller branch, The Rockefeller University, New York, NY, USA

    Jean Laurent Casanova & Jacinta Bustamante

  15. Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France

    Jacinta Bustamante

Authors
  1. Andrés Augusto Arias
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  2. Carlos M. Perez-Velez
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  20. José Luis Franco
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Corresponding author

Correspondence to José Luis Franco.

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The authors declare that they have no conflict of interest.

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Arias, A.A., Perez-Velez, C.M., Orrego, J.C. et al. Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency. J Clin Immunol 37, 732–738 (2017). https://doi.org/10.1007/s10875-017-0435-1

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  • DOI: https://doi.org/10.1007/s10875-017-0435-1

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