Publications by authors named "Elena Seoane"

11 Publications

  • Page 1 of 1

Coronavirus disease 2019 in patients with inborn errors of immunity: An international study.

J Allergy Clin Immunol 2021 Feb 24;147(2):520-531. Epub 2020 Sep 24.

Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, UNSW Sydney, Darlinghurst, Australia. Electronic address:

Background: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense.

Objective: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2.

Methods: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI.

Results: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died.

Conclusions: This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.
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http://dx.doi.org/10.1016/j.jaci.2020.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832563PMC
February 2021

Primary and Secondary Immunodeficiency Diseases in Oncohaematology: Warning Signs, Diagnosis, and Management.

Front Immunol 2019 26;10:586. Epub 2019 Mar 26.

Hospital U. Vall d'Hebron, Barcelona, Spain.

Immunodeficiencies (ID), in particular primary immunodeficiencies (PID), are often associated with haematological manifestations, such as peripheral cytopenias or lymphoproliferative syndromes. Early diagnosis and management have significant prognostic implications. Secondary immunodeficiencies (SID) may also be induced by oncohaematological diseases and their treatments. Haematologists and oncologists must therefore be aware of the association between blood disorders and cancer and ID, and be prepared to offer their patients appropriate treatment without delay. Our aim was to define the warning signs of primary and secondary IDs in paediatric and adult patients with oncohaematological manifestations. A multidisciplinary group of six experts (2 haematologists, 2 immunologists, and 2 paediatricians specializing in ID) conducted a literature review and prepared a document based on agreements reached an in-person meeting. An external group of 44 IDs specialists from all over Spain assessed the document and were consulted regarding their level of agreement. This document identifies the haematological and extra-haematological diseases that should prompt a suspicion of PIDs in adults and children, in both primary care and haematology and oncology departments. Cytopenia and certain lymphoproliferative disorders are key diagnostic pointers. The diagnosis must be based on a detailed clinical history, physical exploration, complete blood count and standard laboratory tests. The immunological and haematological tests included in the diagnostic process will depend on the care level. Patients who are candidates for immunoglobulin replacement therapy must be carefully selected, and treatment should be offered as soon as possible to avoid the development of complications. Finally, this document recommends procedures for monitoring these patients. This document combines scientific evidence with the opinion of a broad panel of experts, and emphasizes the importance of an early diagnosis and treatment to avoid complications. The resulting document is a useful tool for primary care physicians and specialists who see both adult and paediatric patients with oncohaematological diseases.
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http://dx.doi.org/10.3389/fimmu.2019.00586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448689PMC
July 2020

Microbiome and Allergic Diseases.

Front Immunol 2018 17;9:1584. Epub 2018 Jul 17.

Research Laboratory and Allergy Unit, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, Universidad de Málaga, ARADyAL, Malaga, Spain.

Allergic diseases, such as respiratory, cutaneous, and food allergy, have dramatically increased in prevalence over the last few decades. Recent research points to a central role of the microbiome, which is highly influenced by multiple environmental and dietary factors. It is well established that the microbiome can modulate the immune response, from cellular development to organ and tissue formation exerting its effects through multiple interactions with both the innate and acquired branches of the immune system. It has been described at some extent changes in environment and nutrition produce dysbiosis in the gut but also in the skin, and lung microbiome, inducing qualitative and quantitative changes in composition and metabolic activity. Here, we review the potential role of the skin, respiratory, and gastrointestinal tract (GIT) microbiomes in allergic diseases. In the GIT, the microbiome has been proven to be important in developing either effector or tolerant responses to different antigens by balancing the activities of Th1 and Th2 cells. In the lung, the microbiome may play a role in driving asthma endotype polarization, by adjusting the balance between Th2 and Th17 patterns. Bacterial dysbiosis is associated with chronic inflammatory disorders of the skin, such as atopic dermatitis and psoriasis. Thus, the microbiome can be considered a therapeutical target for treating inflammatory diseases, such as allergy. Despite some limitations, interventions with probiotics, prebiotics, and/or synbiotics seem promising for the development of a preventive therapy by restoring altered microbiome functionality, or as an adjuvant in specific immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2018.01584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056614PMC
July 2018

The establishment of cow's milk protein allergy in infants is related with a deficit of regulatory T cells (Treg) and vitamin D.

Pediatr Res 2017 May 18;81(5):722-730. Epub 2017 Jan 18.

Laboratory of Immune-regulation, Hospital General Universitario Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.

Background: Cow's milk protein allergy (CMPA) is the most common food allergy in infants. However, little is known about which specific immune mechanisms are related with the CMPA onset. The objective was to investigate which immune alterations constitute differential factors between allergy and tolerance, and hence could be implicated in the CMPA establishment in infants.

Methods: An extensive analysis of immune subsets, including Treg and cytokine-secreting cells was performed in blood samples from 28 infants younger than 9 mo obtained 1-4 d after the first adverse reaction to milk.

Results: Less than 4 d after first allergic reaction, infants who developed CMPA had decreased Treg counts and increased frequency of IL4-secreting CD4 T cells compared to controls. The deficit of Tregs was correlated with decreased serum levels of vitamin D. Values of Tregs, IL4-secreting cells and vitamin D were good predictors of CMPA diagnosis. Basal vitamin D levels in CMPA infants also predicted those CMPA patients developing spontaneous tolerance in the first year.

Conclusion: Establishment of CMPA in infants was related with lower Treg and vitamin D levels. These immune alterations would be crucial factors behind the CMPA establishment and they could constitute a therapeutic target for treatment of CMPA.
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http://dx.doi.org/10.1038/pr.2017.12DOI Listing
May 2017

[A case study of anaphylaxis in a pregnant woman].

Ginecol Obstet Mex 2014 Mar;82(3):188-93

We report a case of anaphylaxis in a 35+5 week of pregnancy patient who came to the Emergency Room with shortness of breath, hypotension and loss on fetal wellbeing. Due to her medical history and given the clinical picture at that time, an anaphylactic shock was suggested as the most probable diagnose. The administration of dexchlorpheniramine and methylprednisolone resulted in an immediate and positive reaction. Simultaneously, an improvement in the fetus cardiotocographic record was objectified. The patient was hospitalized for 48 hours, after which she was discharged. In case of suspicion of anaphylaxis in a pregnant woman, four aspects should be handled: the severity of the anaphylaxis chart, individual complications regarding a pregnant woman, unfavorable effects of the regularly used treatment during that specific gestation, and the need of fetal extraction based of gestational age.
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March 2014

Lipid and apoprotein profile in HIV-1-infected patients after CD4-guided treatment interruption.

J Acquir Immune Defic Syndr 2008 Aug;48(4):455-9

Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario "Gregorio Marañón," Madrid, Spain.

Objectives: The aims of the present study were to determine if metabolic abnormalities and cytokine derangements are modified in HIV-1-infected patients after 12 months on treatment interruption (TI).

Design: The design of this study was prospective randomized study.

Methods: Longitudinal multicenter study in HIV-1-infected patients with a 12-month follow-up. Patients on stable highly active antiretroviral therapy, with CD4 count >600/microL and HIV RNA <50 copies/mL for at least 6 months, were randomized to interrupt therapy or continue ongoing highly active antiretroviral therapy. Lipids (total cholesterol, triglycerides), apoproteins (A1, B, and E), and adipocytokines (leptin, adiponectin, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, Interleukin-6, Interleukin-8, and tumor necrosis factor-alpha) were measured at baseline and at month 12. Multiplex suspension bead array immunoassay was performed using the Luminex 100 analyzer to identify protein expression in plasma.

Results: Patients who underwent TI (n = 19) had a significant decrease in median cholesterol levels (P < 0.001), while median triglyceride levels remained unchanged. There was a significant decrease in Apo-A1 levels (P = 0.048) and Apo-B levels (P < 0.001) and an increase in tumor necrosis factor-alpha levels (P = 0.034). Given the greater decrease in Apo-B, the ratio Apo-A1/Apo-B increased after 12 months of TI (from 3.4 to 5.1, P = 0.008). We did not find significant variations in leptin or adiponectin levels. In patients who continued on highly active antiretroviral therapy (n = 18), there were no significant changes in any of the measured parameters.

Conclusion: The lipid profile and apoproteins levels change toward a less atherogenic profile after TI, arguing against a lipid-mediated mechanism to explain the increased cardiovascular risk in patients who interrupt treatment.
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http://dx.doi.org/10.1097/QAI.0b013e31817bbc07DOI Listing
August 2008

Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions.

BMC Infect Dis 2008 Feb 26;8:20. Epub 2008 Feb 26.

Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4+, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4+ cell count declines to < 350/microL in CD4-guided antiretroviral treatment interruptions.

Methods: 27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4+ count > 600/microL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4+ cell count to < 350/microL.

Results: After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4+ cell count to < 350/microL. Patients with a CD4+ nadir of < 200 cells/microL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to Mycobacterium tuberculosis purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4+ cell count to < 350/microL.

Conclusion: Both the number (CD4+ nadir) and the functional activity of CD4+ (lymphoproliferative response to PPD) predict the CD4+ decrease associated with discontinuation of ART in patients with controlled viremia.
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http://dx.doi.org/10.1186/1471-2334-8-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291054PMC
February 2008

Short communication: Immune reconstitution after autologous peripheral blood stem cell transplantation in HIV-infected patients: might be better than expected?

AIDS Res Hum Retroviruses 2007 Apr;23(4):543-8

Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo 46, 28007 Madrid, Spain.

We carried out a longitudinal study to analyze the immune recovery of four patients with aggressive HIV-associated lymphoma (HIV+ Ly+) treated with highly active antiretroviral therapy (HAART) and high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT). We also studied three control non-HIV-infected patients with lymphoma (HIV-Ly+) and six HIV patients on HAART without lymphoma (HIV+ Ly-). After 12 months of follow-up, the HIV HIV+Ly+ patients reached the pre-ASCT CD4+ levels, despite a transient decrease after the ASCT. All ASCT patients (HIV+Ly+ and HIV-Ly+) showed an increase in CD4+, CD4+ CD45RO+, and CD4+CD28+ T cells/microl. Although HIV+Ly+ patients had values of CD4+, CD4+CD45RO+, and CD4+CD28+ T cells/microl lower than the HIV-Ly+ patients, their recovery rate over the 12 months after ASCT appeared to be better. HIV+Ly+ patients had higher pre-ASCT plasma IL-7 levels than HIV-Ly+, however, these values decreased after ASCT. All ASCT patients showed a slight increase of TCR rearrangement excision circles (TRECs) and they did not have a different pattern of TREC evolution. We could not find differences between HIV+Ly+ patients 12 months after ASCT and HIV+Ly- in DNA-HIV (copies/10(6) cell). Overall, HIV+Ly+ patients showed an appropriate immune reconstitution 12 months after ASCT, and, interestingly, they had an amount of DNA-HIV copies similar to HIV+Ly- control patients in their CD4+ cells.
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http://dx.doi.org/10.1089/aid.2006.0071DOI Listing
April 2007

Differential biological role of CD3 chains revealed by human immunodeficiencies.

J Immunol 2007 Feb;178(4):2556-64

Inmunología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.

The biological role in vivo of the homologous CD3gamma and delta invariant chains within the human TCR/CD3 complex is a matter of debate, as murine models do not recapitulate human immunodeficiencies. We have characterized, in a Turkish family, two new patients with complete CD3gamma deficiency and SCID symptoms and compared them with three CD3gamma-deficient individuals belonging to two families from Turkey and Spain. All tested patients shared similar immunological features such as a partial TCR/CD3 expression defect, mild alphabeta and gammadelta T lymphocytopenia, poor in vitro proliferative responses to Ags and mitogens at diagnosis, and very low TCR rearrangement excision circles and CD45RA(+) alphabeta T cells. However, intrafamilial and interfamilial clinical variability was observed in patients carrying the same CD3G mutations. Two reached the second or third decade in healthy conditions, whereas the other three showed lethal SCID features with enteropathy early in life. In contrast, all reported human complete CD3delta (or CD3epsilon) deficiencies are in infants with life-threatening SCID and very severe alphabeta and gammadelta T lymphocytopenia. Thus, the peripheral T lymphocyte pool was comparatively well preserved in human CD3gamma deficiencies despite poor thymus output or clinical outcome. We propose a CD3delta > CD3gamma hierarchy for the relative impact of their absence on the signaling for T cell production in humans.
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http://dx.doi.org/10.4049/jimmunol.178.4.2556DOI Listing
February 2007

Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy.

BMC Infect Dis 2006 Jul 13;6:112. Epub 2006 Jul 13.

Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: Recent advances in characterizing the immune recovery of HIV-1-infected people have highlighted the importance of the thymus for peripheral T-cell diversity and function. The aim of this study was to investigate differences in immune reconstitution profiles after highly active antiretroviral therapy (HAART) between HIV-children and adults.

Methods: HIV patients were grouped according to their previous clinical and immunological status: 9 HIV-Reconstituting-adults (HIV-Rec-adults) and 10 HIV-Reconstituting-children (HIV-Rec-children) on HAART with viral load (VL) or=500 cells/microL at least during 6 months before the study and CD4+
Results: HIV-Rec-children had higher T-cell receptor excision circles (TREC) and lower interleukin (IL)-7 levels than HIV-Rec-adults (p < 0.05). When we analyzed Z-score values, HIV-Rec-children had higher TREC Z-score levels (p = 0.03) than HIV-Rec-adults but similar IL-7 Z-score levels. Regarding T-cell subsets, HIV-Rec-children had higher naïve CD4+ (CD4+CD45RA hi+CD27+), naïve CD8+ (CD8+CD45RA hi+CD27+), and memory CD8+ (CD8+CD45RO+) cells/microl than HIV-Rec-adults, but similar memory CD4+ (CD4+CD45RO+) counts. HIV-Rec-children had lower naïve CD8+ Z-score values than HIV-Rec-adults (p = 0.05).

Conclusion: Our data suggest that HIV-Rec-children had better thymic function than HIV-Rec-adults and this fact affects the peripheral T-cell subsets. Thus, T-cell recovery after HAART in HIV-Rec-adults could be the consequence of antigen-independent peripheral T-cell expansion while in HIV-Rec-children thymic output could play a predominant role in immune reconstitution.
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http://dx.doi.org/10.1186/1471-2334-6-112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1534048PMC
July 2006

CD4(+) T-cell immunodeficiency is more dependent on immune activation than viral load in HIV-infected children on highly active antiretroviral therapy.

J Acquir Immune Defic Syndr 2006 Jul;42(3):269-76

Laboratorio de Inmuno-Biología Molecular, Hospital Universitario "Virgen de Rocío," Sevilla, Spain.

Objective: The aim of this study was to analyze the association between CD4(+) depletion and immune activation in HIV-1-infected children on highly active antiretroviral therapy (HAART).

Design And Setting: We carried out a cross-sectional study to determine the profile of several immunologic parameters in 143 children on HAART for more than 24 weeks. Children were stratified according to current immunologic status (CD4 < or =15%, 15%-25%, and > or =25%) and viral load (VL) levels (<400 copies/mL; 400-10,000 copies/mL; and >10,000 copies/mL). We also studied 23 uninfected children as healthy controls.

Methods: Viral load (HIV-RNA copies per milliliter) was quantified using reverse transcriptase polymerase chain reaction molecular assay. T-cell subsets were determined by multiparametric flow cytometry.

Results: HIV-infected children with low percentage of CD4(+) had high memory (CD45RO(+)) and low naive (CD45RA(+)) CD4(+) and CD8(+) T-cell values. Furthermore, children with CD4(+) >25% had similar memory and naive CD4(+) values as the healthy control group, whereas memory and naive CD8(+) subsets were different from the healthy control values. In these HIV-infected children, when CD4(+) was depleted, the amount of naive plus central memory CD8(+) (CD28(+)CD57(-)) cells was decreased, whereas effector CD8(+) (CD28(-)CD57(+)) cells were upregulated, and these values were always higher than healthy control values. Furthermore, children with low percentage of CD4(+) showed significant upregulation of HLA-DR(+)CD38(+) and HLA-DR(+) in both CD4(+) and CD8(+) T-cells independent of VL levels.

Conclusions: Our data suggest that elevated immune activation could be responsible for CD4(+) depletion rather than HIV replication because immunologic status is associated directly to immune activation and not to VL levels in HIV-infected children on HAART.
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http://dx.doi.org/10.1097/01.qai.0000222287.90201.d7DOI Listing
July 2006