Searching for prognostic factors in Common Variable Immunodeficiency based on epidemiological and immunological parameters

Field: Medicine (Health Sciences)

Event Abstract Back to Event Searching for prognostic factors in Common Variable Immunodeficiency based on epidemiological and immunological parameters Jesús A. Álvarez1*, Estefanía Vásquez1, Julio C. Orrego1, Jose L. Franco1, Ruben D. Gómez2 and Claudia Trujillo1 1 Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Colombia 2 Grupo de Epidemiología, Facultad Nacional de Salud Pública, Universidad de Antioquia, Colombia Introduction: Common Variable Immunodeficiency (CVID) is a heterogeneous syndrome characterized by hypogammaglobulinemia, poor response to vaccines and increased susceptibility to recurrent and chronic infections, mostly in respiratory and gastrointestinal tracts. The estimated syndrome incidence is calculated in 1:50,000 life births with a disease burden of 25.21/100.000 disability-adjusted life years (DALY). Disease severity is not only due to infectious diseases but also to cancer, autoimmunity and polyclonal lymphocytic infiltration. Thus, the definition of criteria for disease early detection, classification and prognosis would help to prevent complications further enhancing the patient’s life quality. Methods: A cross-sectional study was designed using the epidemiological, clinical and immunological data obtained from the medical records. In addition, some of the immunological parameters were experimentally confirmed. Descriptive statistic was used to quantitative analyze the different variables. The Intraclass correlation coefficient (ICC) was calculated to evaluate the degree of consistency among different B-cell subpopulations analysis in the same patient. In addition, Mann Whitney U test was used to demonstrate differences in the patients with or without a specific clinical manifestation regarding to the different immunological variables. Results. Thirty patients fulfilled the diagnostic CVID criteria according to the European Society for Immunodeficiencies (ESID) (%females = 33.33). Only 2/22 patients (10%) declared consanguineous parents and 9/28 (32.14%), 9/27 (33.33%), 7/28 (25%) and 6/28 (21.43%) reported family history of any primary immunodeficiency, allergy, malignancies or autoimmunity, respectively. Gender differences were observed in the age of onset and age at diagnosis (males/females Age of onset: 12 vs. 8, IQR 2 – 20 vs. 5 – 38; Age at diagnosis: 26 vs. 39, IQR 15 – 50 vs. 26 – 49, respectively). Past medical history of the patients included mainly asthma and rhinitis (8/28, 28.57%). Respiratory tract infections (acute otitis media, sinusitis and pneumonia) as first symptom were present in 16/29 (55.17%) of the patients. The remaining included diarrhea, skin and mucosal or central nervous system infections and hepatoesplenomegaly. Respiratory (23/29, 79.31%) and gastrointestinal tract (14/29, 48.28%) were the most common sites of infections. However, recurrency was most frequent at respiratory tract, in approximately half of the patients (13/29, 44.83%) and 9/29 (31.03%) suffered from structural damage in the lung (bronchiectasis). Most of the patients have been affected at least once lifelong from a severe infection 25/29 (86.21%), namely: pneumonia (65.55%), meningitis/encephalitis (10.34%), myopericarditis (3.45%), meningitis/sepsis (3.45%) or bone/joint infections (3.45%). Two patients presented pneumonia together with either meningitis/encephalitis or myopericarditis. Noninfectious diseases were also observed in our cohort as follows: 4/28 (14.28%) developed autoimmunity, 5/29 (17.24%) presented with malignances, 7/29 (24.14%) exhibited polyclonal lymphocytic infiltration (persistent hepatosplenomegaly or lymphadenopathy) and 9/27 (33.33%) reported hypothyroidism. As expected, all patients presented with decreased serum levels of IgG and IgA and more than 70% also exhibited diminished IgM at the time of diagnosis. According to the normal ranges established for age, only one patient presented each with either increase or decrease levels of T cells in peripheral blood (PB) but 15 and 22% exhibited decrease B or NK cell numbers in PB, respectively. Measurements of T cell subpopulations revealed diminished CD4+ T cells in 32% with a decreased in central memory and a concomitant increases in effector memory cells in 80%. On the other hand, CD8+ T cells were increased in 19% but central memory cytotoxic cells were decreased in 62%. An increase naïve B cells in PB (72%) was associated with reduced switched memory and marginal zone-like B cells in 88 and 71% of the patients, respectively. Moreover, other alterations as increase transitional (57%) and decrease of CD21+ B cells (35%) were also observed. Interestingly, 80% of the patients showed decreases CD56dim NK cells and 57% presented with augmented proinflamatories monocytes (CD14+CD16+) in PB. The consistency of the B cell subpopulation measurements overtime was confirmed with the calculated ICC=0,89, indicating an almost perfect degree of agreement. Finally, our analyses demonstrated that patients with bronchiectasis presented lower levels of serum IgG at the time of diagnosis (89.3 vs. 203.5 mg/dl, p= 0.05), lower percentage of the classical monocytes (88.9% vs. 95.2%, p=0.05), and higher percentage of CD8+ T cells (43.05% vs. 25.95% p=0.0155) than those without this clinical feature. Patients with autoimmunity showed higher CD21+ B (97.88% vs. 86.46 p=0.0231) and CD56dim NK cells (90.90% vs. 75.78%, p=0.05) but lower T (60.25% vs. 72%, p=0.0379) and CD8+ T cells (17.2% vs. 37.6%, p= 0.0215). Patients with malignancies were more prone to exhibit increase CD21+ B cells (99.12% vs. 89.14%, p=0.0285) and those who development polyclonal lymphocytic infiltration presented with more decreased effector CD4+ T cells (5.4% vs. 8.4%, p=0.037). On the contrary, patients with hypothyroidism displayed higher effector CD4+ T cells (9.35% vs. 6.35%, p=0.00655). Conclusion. This study demonstrated gender differences in the age of onset and age at diagnosis in CVID. Clinical parameters of our cohort are similar to those reported in the literature. Interestingly, we observed not only alterations in B but also in T and NK cell- and monocytes- numbers in PB. Some of these differences are related with the clinical characteristics of the patients and therefore, are potential prognostic factors in CVID. Nevertheless, more detailed investigation is needed to determine causal associations among the immunological variables and clinical manifestations in the context of this immunodeficiency. Acknowledgements Acknowledgment. This research was supported by the sustainability strategy of University of Antioquia 2011-2012 and COLCIENCIAS (grant 1115-569-34426). Sustainability strategy CODI 2013-2014 Grupo de Epidemiología Conflict of interest The authors declare that we have no conflict of interest. Keywords: Common variable immunodeficiency (CVID), pronostico factors, Epidemiological variables, Clinical variables, immunological variables 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: Poster Presentation Topic: Immunodeficiencies Citation: Álvarez JA, Vásquez E, Orrego JC, Franco JL, Gómez RD and Trujillo C (2015). Searching for prognostic factors in Common Variable Immunodeficiency based on epidemiological and immunological parameters. 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.2015.05.00126 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: 12 May 2015; Published Online: 14 Sep 2015. * Correspondence: Mr. Jesús A Álvarez, Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Medellin, Colombia, jaalvarez2009@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jesús A Álvarez Estefanía Vásquez Julio C Orrego Jose L Franco Ruben D Gómez Claudia Trujillo Google Jesús A Álvarez Estefanía Vásquez Julio C Orrego Jose L Franco Ruben D Gómez Claudia Trujillo Google Scholar Jesús A Álvarez Estefanía Vásquez Julio C Orrego Jose L Franco Ruben D Gómez Claudia Trujillo PubMed Jesús A Álvarez Estefanía Vásquez Julio C Orrego Jose L Franco Ruben D Gómez Claudia Trujillo Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.