Event Abstract

Back to Event

Molecular characterization of Primary Immunodeficiency Diseases from the group of Primary Immunodeficiencies in Colombia, 2015: an update.

Carlos A. Arango1, 2, Diego E. Góngora1, Julio C. Orrego1, Jesus A. Alvarez1, Diana P. Fernández1, Jesica L. Rojas1, Margarita M. Velasquez1, 3, Daniel Gonzalez Loaiza1, 2, Carlos J. Montoya1, 4, Marcela Moncada-Vélez1, Yermis C. Rocha1, Gabriel J. Vélez1, Juan A. López1, 2, Pablo J. Patiño1, Claudia M. Trujillo1, Jose L. Franco1 and Andres A. Arias1, 2*
  • 1 Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Colombia
  • 2 Universidad de Antioquia, Grupo de Investigación de Microbiología Básica y Aplicada (MICROBA), Escuela de Microbiología, Colombia
  • 3 Universidad de Antioquia, Centro de Investigaciones Dermatológicas (CIDERM), Colombia
  • 4 Universidad de Antioquia, Grupo de Inmunovirología, Facultad de Medicina, Colombia

Primary Immunodeficiency Diseases (PID) are inborn errors of immunity that affect the production of cells and/or molecules leading to abnormalities in the ontogeny, differentiation or effector function of the immune system. According to the latest report from International Union of Immunological Societies (IUIS) Expert Committee on Primary Immunodeficiency more than 260 disorders have been identified, resulting from mutations in over 300 genes. This number is rapidly growing due to increased clinical awareness and next-generation sequencing technologies. PIDs have variable reported incidence around the world, depending upon the specific disorder. The Latin American Society for Immunodeficiencies (LASID) reported 5606 cases of PIDs. From whom approximately 11% of these cases are from our group in Medellin, Colombia. This work represents an update on the molecular characterization of PID patients from our program of detection and management of Recurrent Infections Syndrome and PID, at the Group of Primary Immunodeficiencies from the University of Antioquia in Medellin-Colombia, between 1994-2015. We performed a retrospective data collection (primary source) using our patient database. This population is represented by 875 people in the age ranges of 0 to 4 (39%), 5 to 19 (49%)and 20 years and older (12%). For the description and analyses of molecular and genetic features of the patients diagnosed with PIDs we use the descriptive statistics using univariate analysis. From our cohort only 71 (8% of total) have been screened for mutations in known PID genes and have a complete molecular and genetic characterization. The PID genetically characterized include: Combined Immunodeficiencies (11/71; 15.5%) which involved mutations at the IL-2RG, ADA, IL-7RA and RAG2 genes in Severe Combined Immunodeficiency (SCID). For the group of Combined Immunodeficiencies with Associated or Syndromic Features, we performed the molecular diagnosis of 9 patients with DiGeorge Syndrome (12.7%), 8 with Hyper-IgE Syndrome (11.3 %) and 3 with Wiskott Aldrich Syndrome (4.2 %) (carrying mutations in TBX1, STAT3 and WAS gene, respectively). Among the Predominantly Antibody Deficiencies, we have characterized 13 patients with X-linked Agammaglobulinemia (due to BTK mutations; 18.3%), three with CD19 deficiency (4.2%), two with CD40L deficiency (2.8 %) and only one patient with TACI deficiency (1.4%). For the Diseases of Immune Dysregulation, 6 patients with Familial Hemophagocytic Lymphohistiocytosis (8.4%) carrying mutations at the PRF1 gene were detected. From the Congenital defects of phagocytes group, seven patients were identified with Chronic Granulomatous Disease due to mutations at CYBB (9.9%), three with ELANE mutations resulting in Congenital Neutropenia (4.2%), two (2.8%) with Mendelian Susceptibility Micobacterial Disease (IFNGR1 and IL12RB1 genes), and one (1.4%) with Shwachman-Diamond Syndrome (SBDS gene). Among the Defects in Innate Immunity, one patient (1.4%) presented with Chronic Mucocutaneous Candidiasis carried STAT1 mutations. Finally, we detected one patient with a Familial Mediterranean Fever, an autoinflammatory disorder (MEFV; 1,4%). Molecular defects included missense, nonsense, deletion, insertion and frame shift mutations. Although a considerable amount of PID patients in our cohort has been genetically characterized, the percentage among the total population remains low. Despite of the difficulties of the Colombian Healthcare System to financially support these procedures, we believe that proper education and knowledge of PID will help to increase awareness and perform promptly immunological and molecular characterization of patients, increasing the registry at the LASID database. Likewise, this will provide us with new perspectives to perform prenatal diagnostic, design specific therapies for these conditions and establish timely protocols for genetic counseling in the affected families.

Acknowledgements

We tanto to thanks Carolyn Franco for her administrative support. Financial support: Colciencias (Grant 576-2013), Jeffrey Modell Foundation and Fundación “Diana García de Olarte” para las Inmunodeficiencias Primarias (FIP), Medellín, Colombia. Colciencias (code 111556934990), Colciencias ECOS-NORD (convenio 219-2013) and CODI (Convenio de pasantía 8700/525/2015).

Keywords: Primary Immunodeficiency Diseases, Molecular diagnostics, inborn errors of immunity, CGD, MSMD

Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.

Presentation Type: Oral Presentation

Topic: Immunodeficiencies

Citation: Arango CA, Góngora DE, Orrego JC, Alvarez JA, Fernández DP, Rojas JL, Velasquez MM, Gonzalez Loaiza D, Montoya CJ, Moncada-Vélez M, Rocha YC, Vélez GJ, López JA, Patiño PJ, Trujillo CM, Franco JL and Arias AA (2015). Molecular characterization of Primary Immunodeficiency Diseases from the group of Primary Immunodeficiencies in Colombia, 2015: an update.. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00353

Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.

The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.

Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.

For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.

Received: 27 May 2015; Published Online: 15 Sep 2015.

* Correspondence: PhD. Andres A Arias, Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Medellin, Antioquia, Colombia, aaugusto.arias@udea.edu.co