Clinical manifestations and approach to the management of patients with common variable immunodeficiency and liver disease.

Purpose: The clinical spectrum of common variable immunodeficiency (CVID) includes predisposition to infections, autoimmune/inflammatory complications and malignancy. Liver disease is developed by a proportion of patients with CVID, but limited evidence is available about its prevalence, pathogenesis and prognostic outcome. This lack of evidence leads to the absence of guidelines in clinical practice. In this study, we aimed at defining the characteristics, course and management of this CVID complication in Spain. Methods: Spanish reference centers were invited to complete a cross-sectional survey. Thirty-eight patients with CVID-related liver disease from different hospitals were evaluated by a retrospective clinical course review. Results: In this cohort, abnormal liver function and thrombocytopenia were found in most of the patients (95% and 79% respectively), in keeping with the higher incidence of abnormal liver imaging and splenomegaly. The most common histological findings included nodular regenerative hyperplasia (NRH) and lymphocytic infiltration, which have been associated with portal hypertension (PHTN) leading to a poorer prognosis. Autoimmune/inflammatory complications occurred in 82% of the CVID patients that developed liver disease and 52% of the patients treated with immunomodulators showed a reduction in the liver function tests' abnormalities during treatment. Among the experts that conducted the survey, there was 80% or more consensus that the workup of CVID-related liver disease requires liver profile, abdominal ultrasound and transient elastography. The majority agreed that liver biopsy should be essential for diagnosis. There was 94% consensus that endoscopic studies should be performed in the presence of PHTN. However, there was 89% consensus that there is insufficient evidence on the management of these patients. Conclusion: Liver disease varies in severity and may contribute substantially to morbidity and mortality in patients with CVID. Hence the importance of close follow-up and screening of this CVID complication to prompt early targeted intervention. Further research is needed to evaluate the pathophysiology of liver disease in patients with CVID to identify personalized treatment options. This study emphasizes the urgent need to develop international guidelines for the diagnosis and management of this CVID complication.

Detection of specific RBD+ IgG+ memory B cells by flow cytometry in healthcare workers and patients with inborn errors of immunity after BNT162b2 m RNA COVID-19 vaccination.

Introduction: Inborn errors of immunity (IEI) are a heterogeneous group of diseases caused by intrinsic defects of the immune system. Estimating the immune competence of immunocompromised patients for an infection risk assessment or after SARS-CoV-2 vaccination constituted a challenge. Methods: The aim of this study was to determine the humoral responses of patients with IEI through a comprehensive analysis of specific receptor-binding domain-positive (RBD+) IgG+ memory B cells (MBCs) by flow cytometry, together with routine S-specific IgG antibodies and QuantiFERON SARS-CoV-2 (T-cell response), before the vaccine and 3 weeks after a second dose. Results and discussion: We first analyzed the percentage of specific RBD+ IgG+ MBCs in healthy healthcare workers. Within the control group, there was an increase in the percentage of specific IgG+ RBD+ MBCs 21 days after the second dose, which was consistent with S-specific IgG antibodies.Thirty-one patients with IEI were included for the pre- and post-vaccination study; IgG+ RBD+ MBCs were not evaluated in 6 patients due to an absence of B cells in peripheral blood. We detected various patterns among the patients with IEI with circulating B cells (25, 81%): an adequate humoral response was observed in 12/25, consider by the detection of positive S-specific IgG antibodies and the presence of specific IgG+ RBD+ MBCs, presenting a positive T-cell response; in 4/25, very low S-specific IgG antibody counts correlated with undetectable events in the IgG+ RBD+ MBC compartment but with positive cellular response. Despite the presence of S-specific IgG antibodies, we were unable to detect a relevant percentage of IgG+ RBD+ MBCs in 5/25; however, all presented positive T-cell response. Lastly, we observed a profound failure of B and T-cell response in 3 (10%) patients with IEI, with no assessment of S-specific IgG antibodies, IgG+ RBD+ MBCs, and negative cellular response. The identification of specific IgG+ RBD+ MBCs by flow cytometry provides information on different humoral immune response outcomes in patients with IEI and aids the assessment of immune competence status after SARS-CoV-2 mRNA vaccine (BNT162b2), together with S-specific IgG antibodies and T-cell responses.

Maintenance of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients after 1273-mRNA SARS-CoV-2 Vaccination.

Continuous evaluation of the coronavirus disease 2019 (COVID-19) vaccine effectiveness in hemodialysis (HD) patients is critical in this immunocompromised patient group with higher mortality rates due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The response towards vaccination in HD patients has been studied weeks after their first and second SARS-CoV-2 vaccination dose administration, but no further studies have been developed in a long-term manner, especially including both the humoral and cellular immune response. Longitudinal studies that monitor the immune response to COVID-19 vaccination in individuals undergoing HD are therefore necessary to prioritize vaccination strategies and minimize the pathogenic effects of SARS-CoV-2 in this high-risk group of patients. We followed up HD patients and healthy volunteers (HV) and monitored their humoral and cellular immune response three months after the second (V2+3M) and after the third vaccination dose (V3+3M), taking into consideration previous COVID-19 infections. Our cellular immunity results show that, while HD patients and HV individuals secrete comparable levels of IFN-γ and IL-2 in ex vivo stimulated whole blood at V2+3M in both naïve and COVID-19-recovered individuals, HD patients secrete higher levels of IFN-γ and IL-2 than HV at V3+3M. This is mainly due to a decay in the cellular immune response in HV individuals after the third dose. In contrast, our humoral immunity results show similar IgG binding antibody units (BAU) between HD patients and HV individuals at V3+3M, independently of their previous infection status. Overall, our results indicate that HD patients maintain strong cellular and humoral immune responses after repeated 1273-mRNA SARS-CoV-2 vaccinations over time. The data also highlights significant differences between cellular and humoral immunity after SARS-CoV-2 vaccination, which emphasizes the importance of monitoring both arms of the immune response in the immunocompromised population.

ECG Identification Based on the Gramian Angular Field and Tested with Individuals in Resting and Activity States.

In the last decade, biosignals have attracted the attention of many researchers when designing novel biometrics systems. Many of these works use cardiac signals and their representation as electrocardiograms (ECGs). Nowadays, these solutions are even more realistic since we can acquire reliable ECG records by using wearable devices. This paper moves in that direction and proposes a novel approach for an ECG identification system. For that, we transform the ECG recordings into Gramian Angular Field (GAF) images, a time series encoding technique well-known in other domains but not very common with biosignals. Specifically, the time series is transformed using polar coordinates, and then, the cosine sum of the angles is computed for each pair of points. We present a proof-of-concept identification system built on a tuned VGG19 convolutional neural network using this approach. We confirm our proposal's feasibility through experimentation using two well-known public datasets: MIT-BIH Normal Sinus Rhythm Database (subjects at a resting state) and ECG-GUDB (individuals under four specific activities). In both scenarios, the identification system reaches an accuracy of 91%, and the False Acceptance Rate (FAR) is eight times higher than the False Rejection Rate (FRR).

A challenging differential diagnosis in a patient with autosomal dominant STAT3 deficiency.

Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by loss-of-function (LOF) mutations in the Signal Transducer and Activator of Transcription 3 (STAT3) gene. In these patients, performing a correct differential diagnosis of pulmonary infections is difficult and challenging, as they usually have atypical presentations. However, establishing a correct diagnostic and therapeutic approach is essential, as pulmonary complications are responsible for high morbidity and mortality rates in these patients. We report the case of a teenage girl with AD-HIES and respiratory symptoms and fever in whom performing a correct differential diagnosis was challenging.

Uncommon Cause of Hemoptysis in a 15-Year-Old Boy.

CASE PRESENTATION: A 15-year-old boy presented with three acute episodes of self-limited hemoptysis. He was being followed by the pediatric pulmonology department for necrotizing pneumonia and a right upper lobe lung abscess with residual pneumatocele 5 years earlier. He had also experienced recurrent perianal abscesses and more than 15 acute suppurative otitis media throughout his life, even after myringotomy and transtympanic drainage; methicillin-sensitive Staphyloccocus aureus was found in a culture of otic exudate. He had no known allergies and was not taking any drugs. The patient's father had presented with more than 20 skin abscesses and was carrier of methicillin-resistant S aureus. After necrotizing pneumonia and along with his family history, the patient had undergone a neutrophil oxidative burst test excluding chronic granulomatous disease; immunoglobulin levels and lymphocyte populations were within normal range.

Humoral and cellular immune response to mRNA SARS-CoV-2 BNT162b2 vaccine in adolescents with rheumatic diseases.

BACKGROUND: Data about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question. OBJECTIVE: To evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group. METHODS: Adolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (n = 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (n = 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins. RESULTS: There were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination. CONCLUSIONS: We conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.

Alicante-Winter Immunology Symposium in Health (A-Wish) and the Boulle-SEI awards: A collaboration between the Spanish Society for immunology, the University of Alicante and the Jean Boulle Group to honor the Balmis Expedition.

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Rapid, scalable assessment of SARS-CoV-2 cellular immunity by whole-blood PCR.

Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. Here we report the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation. The assays are rapid, internally normalized and probe-based: qTACT requires RNA extraction and dqTACT avoids sample preparation steps. Both assays rely on the quantification of CXCL10 messenger RNA, a chemokine whose expression is strongly correlated with activation of antigen-specific T cells. On restimulation of whole-blood cells with SARS-CoV-2 viral antigens, viral-specific T cells secrete IFN-γ, which stimulates monocytes to produce CXCL10. CXCL10 mRNA can thus serve as a proxy to quantify cellular immunity. Our assays may allow large-scale monitoring of the magnitude and duration of functional T cell immunity to SARS-CoV-2, thus helping to prioritize revaccination strategies in vulnerable populations.

Easy approach to detect cell immunity to COVID vaccines in common variable immunodeficiency patients.

BACKGROUND: Patients with primary antibody deficiencies, such as Common Variable Immunodeficiency (CVID), have some problems to assess immune response after coronavirus disease (COVID) vaccination. Cutaneous delayed-type hypersensitivity (DTH) has the potential to be used as a useful, simple, and cheaper tool to assess T-cell (T lymphocyte) function. METHODS: Seventeen patients with CVID, a rare disease, received two doses of the mRNA-based Pfizer-BioNTech COVID-19 vaccine. Humoral Immune Response (HIR) was determined by measuring specific immunoglobulin G (IgG) antibodies, and Cellular Immune Response (CIR) was evaluated using an ex vivo interferon-gamma release assay (IGRA) and in vivo by DTH skin test. RESULTS: Two weeks after the second dose of the vaccine, 12 out of 17 CVID patients have high optical density (OD) ratios of specific anti-spike protein (S) IgG whereas five patients were negative or low. Ex vivo CIR was considered positive in 14 out of 17 S1-stimulated patients. Unspecific stimulation was positive in all 17 patients showing no T-cell defect. A positive DTH skin test was observed in 16 CVID patients. The only patient with negative DTH also had negative ex vivo CIR. CONCLUSIONS: The use of DTH to evaluate CIR was validated with an optimal correlation with the ex vivo CIR. The CIR after vaccination in patients with antibody deficiencies seems to have high precision and more sensitivity to antibodies-based methods in CVID. CLINICAL IMPLICATIONS: There is a remarkable correlation between cutaneous DTH and ex vivo IGRA after COVID vaccination. A COVID-specific skin DTH test could be implemented in large populations. CAPSULE SUMMARY: Cutaneous delayed-type hypersensitivity has the potential to be used as a useful, simple, and cheaper tool to assess T-cell functioning.

Development of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients After 1273-mRNA SARS-CoV-2 Vaccination.

Long-term hemodialysis (HD) patients are considered vulnerable and at high-risk of developing severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection due to their immunocompromised condition. Since COVID-19 associated mortality rates are higher in HD patients, vaccination is critical to protect them. The response towards vaccination against COVID-19 in HD patients is still uncertain and, in particular the cellular immune response is not fully understood. We monitored the humoral and cellular immune responses by analysis of the serological responses and Spike-specific cellular immunity in COVID-19-recovered and naïve HD patients in a longitudinal study shortly after vaccination to determine the protective effects of 1273-mRNA vaccination against SARS-CoV-2 in these high-risk patients. In naïve HD patients, the cellular immune response measured by IL-2 and IFN-É£ secretion needed a second vaccine dose to significantly increase, with a similar pattern for the humoral response. In contrast, COVID-19 recovered HD patients developed a potent and rapid cellular and humoral immune response after the first vaccine dose. Interestingly, when comparing COVID-19 recovered healthy volunteers (HV), previously vaccinated with BNT162b2 vaccine to HD patients vaccinated with 1273-mRNA, these exhibited a more robust immune response that is maintained longitudinally. Our results indicate that HD patients develop strong cellular and humoral immune responses to 1273-mRNA vaccination and argue in favor of personalized immune monitoring studies in HD patients, especially if COVID-19 pre-exposed, to adapt COVID-19 vaccination protocols for this immunocompromised population.

Easy approach to detect cell immunity to COVID vaccines in common variable immunodeficiency patients

Background Patients with primary antibody deficiencies, such as Common Variable Immunodeficiency (CVID), have some problems to assess immune response after coronavirus disease (COVID) vaccination. Cutaneous delayed-type hypersensitivity (DTH) has the potential to be used as a useful, simple, and cheaper tool to assess T-cell (T lymphocyte) function.Methods Seventeen patients with CVID, a rare disease, received two doses of the mRNA-based Pfizer-BioNTech COVID-19 vaccine. Humoral Immune Response (HIR) was determined by measuring specific immunoglobulin G (IgG) antibodies, and Cellular Immune Response (CIR) was evaluated using an ex vivo interferon-gamma release assay (IGRA) and in vivo by DTH skin test.Results Two weeks after the second dose of the vaccine, 12 out of 17 CVID patients have high optical density (OD) ratios of specific anti-spike protein (S) IgG whereas five patients were negative or low. Ex vivo CIR was considered positive in 14 out of 17 S1-stimulated patients. Unspecific stimulation was positive in all 17 patients showing no T-cell defect. A positive DTH skin test was observed in 16 CVID patients. The only patient with negative DTH also had negative ex vivo CIR.Conclusions The use of DTH to evaluate CIR was validated with an optimal correlation with the ex vivo CIR. The CIR after vaccination in patients with antibody deficiencies seems to have high precision and more sensitivity to antibodies-based methods in CVID.Clinical Implications There is a remarkable correlation between cutaneous DTH and ex vivo IGRA after COVID vaccination. A COVID-specific skin DTH test could be implemented in large populations.Capsule Summary Cutaneous delayed-type hypersensitivity has the potential to be used as a useful, simple, and cheaper tool to assess T-cell functioning (AU)

Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals.

The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. In this study, we characterize SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during and after two doses of BNT162b2 vaccination. Our results demonstrate that, while the second dose increases both the humoral and cellular immunity in naive individuals, COVID-19 recovered individuals reach their peak of immunity after the first dose. These results suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.

A Mediation Model between Self-Esteem, Anxiety, and Depression in Sport: The Role of Gender Differences in Speleologists.

The scientific literature on mental health has found an association between physical activity and emotional wellbeing and recommends active leisure activities as a way of keeping stress under control. The purpose of this research study is to analyze the level of anxiety, the symptoms of depression and the level of self-esteem of people practicing speleology, as well as possible gender differences. This paper also attempts to understand whether self-esteem is associated with the presence of symptoms of depression in speleologists and whether anxiety has a mediating effect. We conduct a cross-sectional and descriptive research study with a sampling of 105 adult speleologists. The results reveal that the total mediation model is applicable, as self-esteem has a significant indirect association with depression through trait anxiety, as well as a partial mediation model that is applicable through state anxiety. This means that speleologists with high levels of self-esteem, who appreciate and value themselves adequately, reveal lower levels of trait anxiety, and this negatively influences their levels of depression (that is, a lower level of depressive symptoms). At the same time, speleologists with high levels of self-esteem, who appreciate and value themselves adequately, also reveal lower levels of state anxiety, which again has a negative impact on their levels of depression (with fewer symptoms of depression). Emotions such as anxiety, self-esteem, depression and their collateral effects are international topics of interest, which are relevant for people from all sporting backgrounds; therefore, value should be placed on supporting and carrying out further research into this topic.

The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia.

BACKGROUND: The impact of respiratory virus infection in patients diagnosed with ataxia-telangiectasia (A-T) has not been well studied. METHODS: A prospective case control study was performed at a National Reference Unit for Primary Immunodeficiency in Spain (from November 2018 to July 2019), including patients younger than 20 years. Symptom questionnaires and nasopharyngeal swabs from multiple respiratory viruses' polymerase chain reaction were collected monthly, and between visits in case of symptoms. RESULTS: Twenty-two individuals were included (11 patients; 11 controls); 164 samples were obtained (81 patients; 84 controls). Patients presented respiratory symptoms more frequently compared with controls (26.5% vs. 3.5%; p < 0.01). Viral detection was observed in 23 (27.3%) episodes in patients and in 15 (17.8%) episodes in controls (p = 0.1). Rhinovirus was the most frequent virus in patients and controls (60% and 53.3%, respectively). Episodes with positive viral detection had associated symptoms in 54% of patients and 18% of controls (p = 0.07). However, patients with A-T presented a similar rate of symptoms during episodes with positive and negative viral detection (26% vs. 27%). The median points given for each questionnaire during symptomatic episodes with negative viral detection were 13/23 points, and during symptomatic positive detection, 7.5/23 points (p = 0.1). In the control group, all but two were asymptomatic during positive viral episodes (score: 2/23 and 3/23 points). Symptomatic episodes, with either positive or negative viral detection, were associated with lower IgA and higher IgM titers and higher CD8+ counts (p < 0.05), particularly when these episodes were moderate/severe. CONCLUSIONS: Patients with A-T more frequently present symptomatic viral infections than controls, especially those with lower IgA and higher IgM titers and higher CD8+ counts.

The Association of Parental Interest in Entrepreneurship with the Entrepreneurial Interest of Spanish Youth.

As entrepreneurial interest is believed to represent a causal factor increasing entrepreneurship, research has begun to explore how family systems affect youth entrepreneurial interests. In the present study, we attempt to identify different types of family influence on the entrepreneurial interests of young people. A questionnaire was used to obtain data from 1633 Spanish adolescents (15 to 18 years old) and another questionnaire was used to obtain data from 839 parents. Principal component analysis identified unique family types and revealed that they have differential associations to entrepreneurial interest among youth. These findings reaffirm the influence of family on the entrepreneurial ecosystem and the promotion of an entrepreneurial family culture. This study further suggests that early attention should focus on the detection of entrepreneurial interest among youth so that actions can be implemented in the families to incentivize an entrepreneurial family culture.

Impact of selenium co-administration on methylmercury exposed eleutheroembryos and adult zebrafish (Danio rerio): Changes in bioaccumulation and gene expression.

Mercury still represents one of the most hazardous threats for the aquatic ecosystem due to its high toxicity, and the fact that it can be easily incorporated into the food chain by accumulation in fish as MeHg. On the other hand, selenium is a micronutrient that is part of different antioxidant enzymes that regulate the cellular redox state, and whose complex interaction with Hg has been extensively studied from a toxicological point of view. In order to evaluate the protective effect of Se(IV) co-administration against MeHg accumulation and toxicity, we have selected an in-vivo model at two developmental stages: zebrafish eleutheroembryos and adult fish. Embryos were exposed during 48 h to MeHg (5 or 25 µg/l) and a concentration of Se (IV) representing a molar ratio close to one (2.5 or 12.5 µg/l), while adult zebrafish were exposed during 72 h to either 25 µg/l of MeHg alone or co-exposed with 12.5 µg/l of Se (IV). A significant decrease in MeHg bioaccumulation factor was observed in eleutheroembryos co-exposed to Se(IV). A time-dependent accumulation of MeHg was observed in all the analyzed organs and tissues of adult fish, which was significantly reduced in the muscular tissue and the intestine by Se(IV) co-administration. However, such protection against MeHg bioaccumulation was not maintained in the brain and liver. The data derived from the gene expression analysis also demonstrated the protective effect of Se(IV) against MeHg-induced oxidative stress and the activation of different defense mechanisms by Se(IV) co-administration.

Non-Linear Dynamical Analysis of Resting Tremor for Demand-Driven Deep Brain Stimulation.

Parkinson's Disease (PD) is currently the second most common neurodegenerative disease. One of the most characteristic symptoms of PD is resting tremor. Local Field Potentials (LFPs) have been widely studied to investigate deviations from the typical patterns of healthy brain activity. However, the inherent dynamics of the Sub-Thalamic Nucleus (STN) LFPs and their spatiotemporal dynamics have not been well characterized. In this work, we study the non-linear dynamical behaviour of STN-LFPs of Parkinsonian patients using ε -recurrence networks. RNs are a non-linear analysis tool that encodes the geometric information of the underlying system, which can be characterised (for example, using graph theoretical measures) to extract information on the geometric properties of the attractor. Results show that the activity of the STN becomes more non-linear during the tremor episodes and that ε -recurrence network analysis is a suitable method to distinguish the transitions between movement conditions, anticipating the onset of the tremor, with the potential for application in a demand-driven deep brain stimulation system.

Design and Analysis of a True Random Number Generator Based on GSR Signals for Body Sensor Networks.

Today, medical equipment or general-purpose devices such as smart-watches or smart-textiles can acquire a person's vital signs. Regardless of the type of device and its purpose, they are all equipped with one or more sensors and often have wireless connectivity. Due to the transmission of sensitive data through the insecure radio channel and the need to ensure exclusive access to authorised entities, security mechanisms and cryptographic primitives must be incorporated onboard these devices. Random number generators are one such necessary cryptographic primitive. Motivated by this, we propose a True Random Number Generator (TRNG) that makes use of the GSR signal measured by a sensor on the body. After an exhaustive analysis of both the entropy source and the randomness of the output, we can conclude that the output generated by the proposed TRNG behaves as that produced by a random variable. Besides, and in comparison with the previous proposals, the performance offered is much higher than that of the earlier works.